Cystinosis Mutation Database

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CTNS Gene

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CTNS Protein

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CTNS Variants

CTNS
Variant Map

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Last updated:

223

Total Variants Listed

43

Countries With Data

3,566

Total Alleles Reported

The Cystinosis Mutation Database is designed as a tool to provide cystinosis researchers useful and easily accessible information of CTNS alleles and their geographic distribution based on published reports.

What is Cystinosis?

Cystinosis is an ultra-rare, autosomal recessive disease caused by variants in a gene called CTNS. This gene carries the instructions for a protein called cystinosin, which normally clears a molecule called cystine out of the cell's recycling centres (lysosomes). In cystinosis, a faulty cystinosin protein causes cystine to accumulate within cells throughout the body. This progressively damages multiple organs, especially the kidneys and eyes. It affects an estimated 1 in 100,000 to 200,000 people worldwide, though certain populations have much higher rates due to founder mutations.

Clinical Forms

Infantile Nephropathic

The most severe and common form, typically presenting in infancy with Fanconi syndrome and progressive kidney disease. Accounts for the vast majority of cases (~95%).

Juvenile Nephropathic

Characterised by later onset and slower progression of the disease, with milder renal involvement. Accounts for a small minority of cases (<5%).

Ocular Non-Nephropathic

Characterised by primarily eye involvement with corneal crystal accumulation and photophobia, without renal involvement. It is the rarest form of cystinosis (<1% of cases).

Disease Progression Across Life Stages of Untreated Infantile Nephropathic Cystinosis

Mechanisms of cystinosis

Molecular

Cystinosis is caused by biallelic presence of CTNS variants. These can be deletions, insertions, splice variants, missense, nonsense, or promoter mutations. Loss-of-function variants in CTNS impair production, activity, stability or intracellular localization of cystinosin, the lysosomal cystine transporter. As transporter function is lost, cystine cannot be efficiently exported from lysosomes and progressively accumulates.

Cellular

Cystine accumulates inside lysosomes, which can trigger oxidative stress, altered autophagy, inflammation and cellular dysfunction across multiple tissues. CTNS/cystinosin also participates in interactions with other cellular proteins and signaling pathways, extending its influence beyond cystine transport alone.

Multisystemic

Can affect kidneys, eyes, endocrine organs, thyroid, pancreas, liver, muscles, bone, nervous system and brain. Progressive cystine accumulation may lead to Fanconi syndrome, chronic kidney disease, photophobia, growth impairment, hypothyroidism, diabetes, swallowing difficulties, distal myopathy and neurological complications, making cystinosis a truly multisystem disorder that requires lifelong multidisciplinary care.

Diagnosis

Diagnosis typically combines clinical suspicion with the following three methods:

Measurement of cystine levels in white blood cells
Ophthalmologic examination for corneal cystine crystals
Molecular analysis of the CTNS gene

Current treatment

Cysteamine is the standard disease-modifying therapy for cystinosis and significantly slows disease progression. Its mechanism is straightforward: inside lysosomes, cysteamine reacts with accumulated cystine and converts it into compounds that can leave the lysosome through alternative transport systems. This bypass mechanism lowers intracellular cystine levels, delays organ damage, and significantly improves long-term outcomes when treatment is started early and maintained consistently.

Patients also require long‑term multidisciplinary monitoring and supportive care for renal, ophthalmologic, endocrine and neuromuscular complications.

Timeline of Key Discoveries

A brief history of the scientific and therapeutic milestones that have shaped our understanding and treatment of cystinosis.

1903

//

First clinical description of the disease^[1].

1967

Cystine accumulation is first identified inside patient cells^[2].

1976

Cysteamine is identified as a cystine-depleting agent^[3].

1982

The defective lysosomal cystine transport mechanism is demonstrated^[4].

1987

First clinical trial confirms cysteamine slows kidney decline^[5].

1994

The FDA approves oral cysteamine (Cystagon)^[6].

1997

The EMA approves oral cysteamine (Cystagon) in the EU^[7].

1998

The CTNS gene is discovered^[8].

2001

Cystinosin is identified as an H⁺-driven lysosomal cystine transporter^[9].

2012

Cysteamine eye drops (Cystaran) are approved in the US^[10].

2013

Delayed-release oral cysteamine (Procysbi) is approved in the US and EU^[11].

2017

Cysteamine eye drops (Cystadrops) are approved in the EU^[12].

2019

First patient is treated in a first-in-human hematopoietic stem-cell gene therapy trial^[13].

2022

The 3D structure of cystinosin is solved^[14].

2026

International clinical practice guidelines with graded, evidence-based recommendations are published^[15].

Cystinosis Patient Organizations

The following patient and family organizations offer support, information and community for people affected by cystinosis around the world.

Europe

Cystinosis Network EuropeEurope (umbrella)

AIRG-FranceFrance

Cystinose-Selbsthilfe e.V.Germany

Cystinosis IrelandIreland

Associazione Cistinosi ItaliaItaly

Cystinose Groep Nederland en VlaanderenNetherlands & Belgium (Flanders)

Asociación Cistinosis España (ACE)Spain

Cystinosis Foundation UKUnited Kingdom

Rest of the World

Cystinosis Research NetworkUnited States

Cystinosis Patient and Family AssociationJapan

Cystinosis Foundation South AfricaSouth Africa

Asociación Mexicana de Cistinosis (AMECIAC)Mexico

The Australian Cystinosis FoundationAustralia

Cystinosis Foundation IndiaIndia

SİSTİNDER (Cystinosis Patients Association)Turkey

References

Abderhalden, E. Familiäre Cystindiathese. Z. Physiol. Chem. 38, 557-561 (1903).
Schneider, J.A. et al. Increased free-cystine content of fibroblasts cultured from patients with cystinosis. Biochem. Biophys. Res. Commun. 29, 527-531 (1967).
Thoene, J.G. et al. Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo. J. Clin. Invest. 58, 180-189 (1976).
Gahl, W.A. et al. Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science 217, 1263-1265 (1982).
Gahl, W.A. et al. Cysteamine therapy for children with nephropathic cystinosis. N. Engl. J. Med. 316, 971-977 (1987).
U.S. Food and Drug Administration. Approval of Cystagon (cysteamine bitartrate) for nephropathic cystinosis, NDA 020392 (1994).
European Medicines Agency. Cystagon (mercaptamine bitartrate): EU/1/97/039, European Public Assessment Report, date of first authorisation 23 June 1997.
Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Kalatzis, V. et al. Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter. EMBO J. 20, 5940-5949 (2001).
U.S. Food and Drug Administration. Approval of Cystaran (cysteamine ophthalmic solution) for corneal cystine crystals, NDA 200740 (2012).
Langman, C.B. et al. A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety. Clin. J. Am. Soc. Nephrol. 7, 1112-1120 (2012).
Liang, H. et al. A New Viscous Cysteamine Eye Drops Treatment for Ophthalmic Cystinosis: An Open-Label Randomized Comparative Phase III Pivotal Study. Invest. Ophthalmol. Vis. Sci. 58, 2275-2283 (2017).
Cherqui, S. Hematopoietic Stem Cell Gene Therapy for Cystinosis: From Bench-to-Bedside. Cells 10, 3273 (2021).
Guo, X. et al. Structure and mechanism of human cystine exporter cystinosin. Cell 185, 3739-3752 (2022).
Hohenfellner, K. et al. Clinical practice recommendations for the diagnosis and management of nephropathic cystinosis. Nat. Rev. Nephrol. 22, 651-670 (2026).
Jamalpoor, A. et al. Molecular Mechanisms and Treatment Options of Nephropathic Cystinosis. Trends Mol. Med. 27, 673-686 (2021).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Carneiro, A. et al. Advances in Pharmacological Treatments for Cystinosis: Cysteamine and Its Alternatives. ACS Pharmacol. Transl. Sci. 9, 272-281 (2026).
Markello, T.C. et al. Improved renal function in children with cystinosis treated with cysteamine. N. Engl. J. Med. 328, 1157-1162 (1993).
Gahl, W.A. et al. Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. Mol. Genet. Metab. 71, 100-120 (2000).

CTNS Gene

An interactive overview of the CTNS gene structure and coding sequence, and where reported mutations fall across each.

Gene Structure & Mutation Map

The diagram below shows the full genomic span of CTNS (~26.6 kb), including its promoter region, all 12 exons (light gray = non-coding exons 1–2; colored = coding exons 3–12) and the 11 introns between them, drawn approximately to scale. Use the buttons below to show or hide each type of mutation that spans genomic (non-coding) sequence. Hover a marker for details, click it to open its record.

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Coding Sequence & Mutation Map

The diagram below shows the 10 coding exons of CTNS (exons 3–12; exons 1–2 are non-coding and not shown here) laid out along both the amino acid position and the cDNA (nucleotide) position of the transcript. Use the buttons below to show or hide each type of reported mutation. Hover a marker for details, click it to open its record.

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Gene Details

The information below is sourced from official, publicly maintained genetic databases — NCBI Gene, HGNC, Ensembl, and OMIM. Follow the links to consult each source directly.

Official symbol: CTNS
Official full name: cystinosin, lysosomal cystine transporter
Aliases: CTNS-LSB, PQLC4, SLC66A4
Gene type: Protein-coding
Cytogenetic location: 17p13.2
Genomic coordinates (GRCh38): chr17:3,636,459–3,663,103 (~26.6 kb)
Exon count: 12 (exons 1–2 are non-coding; exons 3–12 are coding)
MANE Select transcript: NM_004937.3 / ENST00000046640.9
Reference protein: NP_004928 (UniProt O60931)
HGNC ID: HGNC:2518
NCBI Gene ID: 1497
Ensembl Gene ID: ENSG00000040531
OMIM gene entry: 606272
OMIM phenotype (nephropathic cystinosis): 219800
Promoter region: approximately nucleotides -316 to +1 relative to the transcription start site, containing an Sp1 regulatory element around -299 to -293; this region is shared with the adjacent gene CARKL/SHPK

Official sources

NCBI Gene → HGNC → Ensembl → OMIM (gene) → OMIM (phenotype) → UniProt → ClinVar →

CTNS Protein Structure

Explore the predicted 3D structure of cystinosin, the lysosomal cystine transporter affected in cystinosis.

Cystinosin (CTNS) — AlphaFold Predicted Structure

Cystinosin is a 367-amino-acid, seven-transmembrane domain protein that exports cystine out of lysosomes, driven by the lysosomal H+ electrochemical gradient. Loss-of-function variants in CTNS disrupt this transport, causing cystine to accumulate inside lysosomes.

The model below is a predicted structure from the AlphaFold Protein Structure Database (UniProt accession O60931). Drag to rotate and scroll to zoom.

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Structure prediction source: EMBL-EBI AlphaFold Protein Structure Database. Viewer: 3Dmol.js. Mutation markers indicate the position of the original (wild-type) amino acid affected by each variant; the structure is not remodeled to reflect the mutant amino acid.

Additional Protein Information

The details below are sourced from The Human Protein Atlas, a publicly available reference resource for exploring human proteins. Visit the original page for the full interactive protein browser, splice variant comparisons, and population/clinical variant overlays: proteinatlas.org/ENSG00000040531-CTNS/structure.

Gene name: CTNS
Synonyms: CTNS-LSB, PQLC4, SLC66A4
Gene description: Cystinosin, lysosomal cystine transporter
Protein class: Transporters, Disease related genes, Potential drug targets
Chromosome location: 17p13.2 (3,636,459–3,663,103 bp)
Number of protein-coding transcripts: 10 (canonical: CTNS-201, UniProt O60931)
Protein length & mass (canonical isoform): 367 aa, 41.7 kDa
Predicted transmembrane regions: 7
Predicted location: Membrane, Intracellular
Subcellular location: Localized to the vesicles
Tissue specificity (RNA): Low tissue specificity
Single cell type specificity: Cell type enhanced (cardiomyocytes, epicardial cells, platelets)
Protein evidence: Evidence at protein level
Structures available: 10 protein structures listed for CTNS on the Human Protein Atlas structure page

On the original Human Protein Atlas page, the structure is displayed using the NGL Viewer and can be recoloured by confidence, residue index, or overlaid with population/clinical variants and AlphaMissense pathogenicity predictions for each of the gene's splice variants.

Search CTNS Variants

223 Reported CTNS variants

191

Infantile

16

Juvenile

7

Ocular

7

Unclassified

Unpublished clinical correlation

2

Inconclusive

Conflicting clinical correlation

A mutation is classified as Juvenile or Ocular if the presence of at least one allele carrying that mutation has been consistently reported to cause the corresponding clinical form of cystinosis.

Filters

Mutation Explorer

Search, filter and rank CTNS variants by report frequency, classification, genomic location and variant type.

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🌐 Click a mutation name to view its details, reported geographic distribution, and references.

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Nucleotide Change	Protein Change	Exon/ Intron	Variant Type	Clinical Form	% Alleles	Published Alleles	AVI (Phred)	ClinVar Classification
57 kb del.	Large genomic deletion	Exons 1-10	Deletion	Infantile	46.89%	1672	—	Pathogenic
c.681G>A	Splicing variant	Exon 9	Splice site	Infantile	5.72%	204	25.83	Pathogenic
c.18_21delGACT	p.Thr7Phefs*7	Exon 3	Deletion	Infantile	5.66%	202	—	Pathogenic
c.1015G>A	p.Gly339Arg	Exon 12	Missense	Infantile	4.94%	176	30.30	Pathogenic
c.414G>A	p.Trp138*	Exon 7	Nonsense	Infantile	2.19%	78	46.07	Pathogenic
c.681+1G>A	Splicing variant	Intron	Splice site	Infantile	1.57%	56	34.26	Pathogenic
c.829dupA	p.Thr277Asnfs*19	Exon 10	Insertion	Infantile	1.40%	50	—	Pathogenic
c.926dupG	p.Ser310Glnfs*55	Exon 11	Insertion	Infantile	1.40%	50	—	Pathogenic
c.971-12G>A	Splicing variant	Intron	Splice site	Infantile	1.37%	49	25.92	Pathogenic
c.198_218del21	p.Ile67_Pro73del	Exon 5	Deletion	Juvenile	1.21%	43	—	Pathogenic/Likely Pathogenic
c.922G>A	p.Gly308Arg	Exon 11	Missense	Infantile	1.18%	42	31.93	Pathogenic/Likely Pathogenic
c.451A>G	p.Arg151Gly	Exon 7	Missense	Infantile	1.09%	39	25.55	Likely Pathogenic
c.646dupA	p.Thr216Asnfs*12	Exon 9	Insertion	Infantile	0.79%	28	—	Pathogenic
c.422C>T	p.Ser141Phe	Exon 7	Missense	Infantile	0.67%	24	31.31	Pathogenic/Likely Pathogenic
c.140+1G>T	Splicing variant	Intron	Splice site	Infantile	0.62%	22	34.62	Pathogenic/Likely Pathogenic
c.518A>G	p.Tyr173Cys	Exon 8	Missense	Infantile	0.62%	22	25.17	Pathogenic
c.771_793del23	p.Gly258Serfs*30	Exon 10	Deletion	Infantile	0.59%	21	—	Pathogenic
c.696dupC	p.Val233Argfs*63	Exon 10	Insertion	Infantile	0.59%	21	—	Pathogenic
c.283G>T	p.Gly95*	Exon 6	Nonsense	Infantile	0.56%	20	45.84	Pathogenic
c.473T>C	p.Leu158Pro	Exon 8	Missense	Infantile	0.56%	20	27.54	Pathogenic/Likely Pathogenic
c.809_811delCCT	p.Ser270del	Exon 10	Deletion	Infantile	0.53%	19	—	Pathogenic/Likely Pathogenic
c.1013T>G	p.Leu338Arg	Exon 12	Missense	Infantile	0.50%	18	27.18	Pathogenic
c.141-22A>G	Splicing variant	Intron	Splice site	Infantile	0.48%	17	26.24	Undefined
c.2T>C	p.Met1Thr	Exon 3	Missense	Infantile	0.48%	17	27.44	Undefined
c.696_697dupCG	p.Val233Alafs*21	Exon 10	Insertion	Infantile	0.45%	16	—	Pathogenic
c.416C>T	p.Ser139Phe	Exon 7	Missense	Juvenile	0.42%	15	31.42	Pathogenic/Likely Pathogenic
c.559_561+24del27	p.Lys187del	Exon 8	Deletion	Infantile	0.39%	14	—	Pathogenic/Likely Pathogenic
c.834_842delGGTCAAGTA	p.Val279_Tyr281del	Exon 10	Deletion	Infantile	0.39%	14	—	Undefined
ex. 4-5	Large genomic deletion	Exons 4-5	Deletion	Infantile	0.36%	13	—	Undefined
c.613G>A	p.Asp205Asn	Exon 9	Missense	Infantile	0.36%	13	29.88	Pathogenic
c.969C>G	p.Asn323Lys	Exon 11	Missense	Juvenile	0.36%	13	16.70	Pathogenic
~13 kb incl. ex. 1-3 3'brk E3I3+183	Large genomic deletion	Exons 1-3	Deletion	Infantile	0.34%	12	—	Undefined
c.323delA	p.Gln108Argfs*10	Exon 6	Deletion	Infantile	0.34%	12	—	Pathogenic
c.665A>G	p.Gln222Arg	Exon 10	Missense	Infantile	0.31%	11	25.99	Likely Pathogenic
c.141-24T>C	Splicing variant	Intron	Splice site	Infantile	0.28%	10	24.10	Pathogenic
c.225+3A>T	Splicing variant	Intron	Splice site	Infantile	0.28%	10	29.67	Pathogenic/Likely Pathogenic
c.682-1G>T	Splicing variant	Intron	Splice site	Infantile	0.28%	10	34.16	Pathogenic/Likely Pathogenic
c.433C>T	p.Gln145*	Exon 7	Nonsense	Infantile	0.28%	10	44.90	Pathogenic
c.314_317delACTC	p.His105Profs*12	Exon 6	Deletion	Infantile	0.25%	9	—	Pathogenic
c.922insG	p.S310Qfs54	Exon 11	Insertion	Infantile	0.25%	9	—	Undefined
c.261T>A	p.Phe87Leu	Exon 6	Missense	Infantile	0.25%	9	24.54	Undefined
c.382C>T	p.Gln128*	Exon 7	Nonsense	Infantile	0.25%	9	42.39	Pathogenic/Likely Pathogenic
c.61+5G>A	Splicing variant	Intron	Splice site	Infantile	0.22%	8	37.40	Pathogenic/Likely Pathogenic
c.699_700delGT	p.Ser234Leufs*61	Exon 10	Deletion	Infantile	0.22%	8	—	Pathogenic
c.960delC	p.Tyr321Thrfs*8	Exon 11	Deletion	Infantile	0.22%	8	—	Undefined
c.589G>A	p.Gly197Arg	Exon 9	Missense	Ocular	0.22%	8	33.42	Pathogenic/Likely Pathogenic
c.357_360del	p.Ser120AlafsX6	Exon 7	Deletion	Infantile	0.20%	7	—	Undefined
-295 G>C	Promoter region variant	Promoter	Promoter	Infantile	0.20%	7	—	Undefined
c.923G>T	p.Gly308Val	Exon 11	Missense	Infantile	0.20%	7	31.30	Pathogenic
c.461+1G>T	Splicing variant	Intron	Splice site	Infantile	0.17%	6	31.65	Undefined
c.970+2T>C	Splicing variant	Intron	Splice site	Juvenile	0.17%	6	33.19	Pathogenic
>1.7kb incl promoter & non-coding ex. 1-2	Large genomic deletion	Exons 1-2	Deletion	Infantile	0.17%	6	—	Undefined
c.206_210delTCCTT	p.Ile69Argfs*5	Exon 5	Deletion	Infantile	0.17%	6	—	Pathogenic
c.257_258delCT	p.Ser86Phefs*38	Exon 6	Deletion	Infantile	0.17%	6	—	Pathogenic
c.295_298delGTTT	p.Val99Ilefs*18	Exon 6	Deletion	Infantile	0.17%	6	—	Undefined
c.518_519delAC	p.Tyr173*	Exon 8	Deletion	Infantile	0.17%	6	—	Undefined
c.519_520delCA	p.Tyr173*	Exon 8	Deletion	Infantile	0.17%	6	—	Pathogenic
c.992delG	p.Gly331Glufs*36	Exon 12	Deletion	Infantile	0.17%	6	—	Undefined
c.140+2T>C	Splicing variant	Intron	Splice site	Infantile	0.14%	5	33.14	Pathogenic/Likely Pathogenic
c.569_577delTTCTCCTCA	p.Phe190*	Exon 9	Deletion	Infantile	0.14%	5	—	Undefined
c.741delC	p.Phe247Leufs*6	Exon 10	Deletion	Infantile	0.14%	5	—	Pathogenic
c.530A>G	p.Asn177Ser	Exon 8	Missense	Juvenile	0.14%	5	22.18	Likely Pathogenic
c.734G>A	p.Trp245*	Exon 10	Nonsense	Infantile	0.14%	5	36.72	Pathogenic
c.785G>A	p.Trp262*	Exon 10	Nonsense	Infantile	0.14%	5	40.18	Likely Pathogenic
c.969C>A	p.Asn323Lys	Exon 11	Missense	Juvenile	0.14%	5	23.38	Undefined
c.1001C>A	p.Thr334Asn	Exon 12	Missense	Inconclusive	0.14%	5	28.38	Uncertain Significance
c.329G>T	Splicing variant	Exon 6	Splice site	Inconclusive	0.11%	4	31.58	Pathogenic
c.901-1G>C	Splicing variant	Intron	Splice site	Infantile	0.11%	4	—	Undefined
>4194bp incl ex. 1-3	Large genomic deletion	Exons 1-3	Deletion	Infantile	0.11%	4	—	Undefined
10217 bp, c.62-1083_551	Large genomic deletion	Exons 4-8	Deletion	Infantile	0.11%	4	—	Undefined
c.1025_1048del24	p.Ser342_Phe349del	Exon 12	Deletion	Infantile	0.11%	4	—	Undefined
c.492_515del24	p.Leu165_Ala172del	Exon 8	Deletion	Infantile	0.11%	4	—	Undefined
ex. 5	Large genomic deletion	Exon 5	Deletion	Infantile	0.11%	4	—	Undefined
c.60_61delTG	p.Cys20*	Exon 3	Deletion	Infantile	0.11%	4	—	Pathogenic
c.120delC	p.Asn41Thrfs*10	Exon 4	Deletion	Infantile	0.11%	4	—	Pathogenic
c.291_294delTACT	p.Thr98Phefs*19	Exon 6	Deletion	Infantile	0.11%	4	—	Undefined
c.561+1delG	Splicing variant	Intron	Splice site	Infantile	0.11%	4	—	Pathogenic/Likely Pathogenic
c.614_616delACG	p.Asp205del	Exon 9	Deletion	Infantile	0.11%	4	—	Undefined
c.956_956delA	p.Q319RfsX10	Exon 11	Deletion	Infantile	0.11%	4	—	Undefined
c.1027_1038del12	p.Ile343_Asp346del	Exon 12	Deletion	Infantile	0.11%	4	—	Pathogenic/Likely Pathogenic
c.92_93insG	p.Val32Argfs*28	Exon 4	Insertion	Infantile	0.11%	4	—	Undefined
c.516dupC	p.Tyr173Leufs*55	Exon 8	Insertion	Infantile	0.11%	4	—	Pathogenic
c.124G>A	p.Val42Ile	Exon 4	Missense	Juvenile	0.11%	4	6.20	Benign/Likely Benign
c.250A>G	p.Asn84Asp	Exon 5	Missense	Infantile	0.11%	4	0.32	Undefined
c.470G>A	p.Gly157Asp	Exon 8	Missense	Infantile	0.11%	4	30.21	Undefined
c.517T>C	p.Tyr173His	Exon 8	Missense	Infantile	0.11%	4	27.24	Likely Pathogenic
c.599C>T	p.Pro200Leu	Exon 9	Missense	Juvenile	0.11%	4	25.31	Undefined
c.664C>T	p.Gln222*	Exon 10	Nonsense	Infantile	0.11%	4	39.46	Undefined
c.853-3C>G	Splicing variant	Intron	Splice site	Ocular	0.08%	3	23.08	Pathogenic
c.61_61+2delGGT	Splicing variant	Exon 3	Splice site	Infantile	0.08%	3	—	Pathogenic/Likely Pathogenic
c.325_329delACCGG	p.Thr109Profs*14	Exon 6	Deletion	Infantile	0.08%	3	—	Undefined
c.15G>A	p.Trp5*	Exon 3	Nonsense	Infantile	0.08%	3	43.85	Pathogenic
c.73A>T	p.Ser25Cys	Exon 4	Missense	Infantile	0.08%	3	8.14	Likely Pathogenic
c.839A>G	p.Lys280Arg	Exon 10	Missense	Juvenile	0.08%	3	36.92	Pathogenic/Likely Pathogenic
c.870C>G	p.Tyr290*	Exon 11	Nonsense	Infantile	0.08%	3	35.26	Pathogenic/Likely Pathogenic
c.923G>A	p.Gly308Glu	Exon 11	Missense	Infantile	0.08%	3	31.15	Undefined
c.61+5G>T	Splicing variant	Intron	Splice site	Infantile	0.06%	2	37.18	Undefined
c.140+5G>A	Splicing variant	Intron	Splice site	Infantile	0.06%	2	29.16	Undefined
c.225+5GT>CC	Splicing variant	Intron	Splice site	Infantile	0.06%	2	—	Undefined
c.462-10C>G	Splicing variant	Intron	Splice site	Juvenile	0.06%	2	24.84	Undefined
c.561+1G>T	Splicing variant	Intron	Splice site	Infantile	0.06%	2	30.42	Undefined
c.853-1G>A	Splicing variant	Intron	Splice site	Infantile	0.06%	2	28.89	Likely Pathogenic
c.971-1G>C	Splicing variant	Intron	Splice site	Infantile	0.06%	2	30.43	Likely Pathogenic
15kb	Large genomic deletion	Exons 1-3	Deletion	Infantile	0.06%	2	—	Undefined
20,327bp incl ex. 1-5 & part of intron 1 of CARKL	Large genomic deletion	Exons 1-5	Deletion	Infantile	0.06%	2	—	Undefined
c.61+2406_225+3028del9287	p.Glu21Glyfs*49	Exons 4-5	Deletion	Infantile	0.06%	2	—	Undefined
c.62-1083_551del10216	p.Glu21Alafs*15	Exons 4-8	Deletion	Infantile	0.06%	2	—	Undefined
ex. 6-13 g.3558266-3565849)	Large genomic deletion	Exons 6-13	Deletion	Infantile	0.06%	2	—	Undefined
ex. 6-7 g.(3558266-3558736)	Large genomic deletion	Exons 6-7	Deletion	Infantile	0.06%	2	—	Undefined
incl. ex. 4-5 g(3550706-3552123)	Large genomic deletion	Exons 4-5	Deletion	Infantile	0.06%	2	—	Undefined
ex. 3 c.(-20+1_19-1)_(61+1_62-1)	Large genomic deletion	Exon 3	Deletion	Infantile	0.06%	2	—	Undefined
c.40delC	p.Leu14*	Exon 3	Deletion	Infantile	0.06%	2	—	Pathogenic
c.61_61+1delinsCT	p.Glu21LeufsTer39	Exon 3	Splice site	Infantile	0.06%	2	—	Undefined
c.225+5_225+6delCT/insCC	Splicing variant	Exon 5	Splice site	Juvenile	0.06%	2	—	Undefined
c.280delG	p.Val94Leufs*24	Exon 6	Deletion	Infantile	0.06%	2	—	Undefined
c.297_312del	p.Tyr100ThrfsX13	Exon 6	Deletion	Infantile	0.06%	2	—	Undefined
c.320_323delATCA	p.Asn107Argfs*10	Exon 6	Deletion	Infantile	0.06%	2	—	Pathogenic
c.329+1delG	Splicing variant	Intron	Splice site	Infantile	0.06%	2	—	Undefined
c.423delC	p.Phe142Serfs*5	Exon 7	Deletion	Infantile	0.06%	2	—	Likely Pathogenic
c.463_464delGT	p.Val155Hisfs*72	Exon 8	Deletion	Infantile	0.06%	2	—	Undefined
c.529delA	p.N177Tfs*	Exon 8	Deletion	Infantile	0.06%	2	—	Undefined
c.558_585del	p.Lys187ThrfsX3	Exon 9	Deletion	Unclassified	0.06%	2	—	Undefined
c.619del	p.Phe207SerfsX11	Exon 9	Deletion	Infantile	0.06%	2	—	Undefined
c.681+7delC	Splicing variant	Intron	Splice site	Infantile	0.06%	2	—	Undefined
c.751_754delACCAinsCG	Large genomic deletion	Exon 10	Deletion	Infantile	0.06%	2	—	Undefined
c.751_752del	p.Thr251Hisfs*44	Exon 10	Deletion	Infantile	0.06%	2	—	Pathogenic
c.770_792del23	fsN288X	Exon 10	Deletion	Infantile	0.06%	2	—	Undefined
c.807_809delCTC	p.Ser270del	Exon 10	Deletion	Infantile	0.06%	2	—	Undefined
c.-303 TG Ins	Promoter region variant	Promoter	Promoter	Ocular	0.06%	2	—	Undefined
c.140+2dupT	Splicing variant	Intron	Splice site	Infantile	0.06%	2	—	Conflicting
c.152_153insCT	p.Ala52Leufs*5	Exon 5	Insertion	Infantile	0.06%	2	—	Pathogenic
c.292dupA	p.Thr98Asnfs*27	Exon 6	Insertion	Infantile	0.06%	2	—	Pathogenic
c.330-14_441dup	Splicing variant	Intron	Splice site	Infantile	0.06%	2	—	Undefined
c.660_661insT	p.Val221Cysfs*7	Exon 9	Insertion	Infantile	0.06%	2	—	Undefined
c.969dupC	p.Asp324ArgfsX41	Exon 11	Insertion	Infantile	0.06%	2	—	Undefined
c.971_972insC	p.Q325PfsX40	Exon 12	Insertion	Infantile	0.06%	2	—	Undefined
-303G>T	Promoter region variant	Promoter	Promoter	Ocular	0.06%	2	—	Undefined
c.1A>C	p.Met1Leu	Exon 3	Missense	Infantile	0.06%	2	30.13	Undefined
c.14G>A	p.Trp5*	Exon 3	Nonsense	Infantile	0.06%	2	43.82	Pathogenic
c.262C>A	p.Gln88Lys	Exon 6	Missense	Infantile	0.06%	2	23.57	Uncertain Significance
c.397A>T	p.Ile133Phe	Exon 7	Missense	Infantile	0.06%	2	21.20	Undefined
c.416C>A	p.Ser139Tyr	Exon 7	Missense	Infantile	0.06%	2	31.95	Undefined
c.506G>A	p.Gly169Asp	Exon 8	Missense	Infantile	0.06%	2	30.39	Likely Pathogenic
c.627C>A	p.Ser209Arg	Exon 9	Missense	Infantile	0.06%	2	26.05	Undefined
c.705G>A	p.Trp235*	Exon 10	Nonsense	Infantile	0.06%	2	36.91	Undefined
c.809C>T	p.Ser270Phe	Exon 10	Missense	Infantile	0.06%	2	30.26	Likely Pathogenic
c.852G>T	p.Gln284His	Exon 10	Missense	Infantile	0.06%	2	50.79	Undefined
c.850C>T	p.Gln284*	Exon 10	Nonsense	Infantile	0.06%	2	46.20	Likely Pathogenic
c.864C>A	p.Asn288Lys	Exon 11	Missense	Infantile	0.06%	2	26.77	Likely Pathogenic
c.873C>G	p.Tyr291*	Exon 11	Nonsense	Infantile	0.06%	2	40.26	Undefined
c.890G>A	p.Trp297*	Exon 11	Nonsense	Infantile	0.06%	2	39.61	Pathogenic
c.914A>G	p.Asp305Gly	Exon 11	Missense	Infantile	0.06%	2	28.82	Uncertain Significance
c.913G>T	p.Asp305Tyr	Exon 11	Missense	Infantile	0.06%	2	31.49	Undefined
c.922G>C	p.Gly308Arg	Exon 11	Missense	Infantile	0.06%	2	34.03	Pathogenic
c.1009G>A	p.Gly337Arg	Exon 12	Missense	Infantile	0.06%	2	30.93	Undefined
c.1013T>C	p.Leu338Pro	Exon 12	Missense	Infantile	0.06%	2	27.66	Undefined
c.1062C>A	p.Phe354Leu	Exon 12	Missense	Infantile	0.06%	2	28.01	Uncertain Significance
c.61-61+2delGGT	Splicing variant	Intron	Splice site	Infantile	0.03%	1	—	Undefined
c.141-1G>A	Splicing variant	Intron	Splice site	Infantile	0.03%	1	33.30	Pathogenic/Likely Pathogenic
c.225+1G>A	Splicing variant	Intron	Splice site	Infantile	0.03%	1	34.02	Pathogenic
c.225+5G>A	Splicing variant	Intron	Splice site	Infantile	0.03%	1	34.04	Likely Pathogenic
c.226-3C>G	Splicing variant	Intron	Splice site	Infantile	0.03%	1	27.87	Likely Pathogenic
c.329G>C	Splicing variant	Exon 6	Splice site	Juvenile	0.03%	1	30.36	Likely Pathogenic
c.329+2T>C	Splicing variant	Intron	Splice site	Juvenile	0.03%	1	27.65	Pathogenic
c.562-1G>C	Splicing variant	Intron	Splice site	Infantile	0.03%	1	32.34	Likely Pathogenic
c.853-7G>A	Splicing variant	Intron	Splice site	Unclassified	0.03%	1	25.00	Undefined
c.853-2A>G	Splicing variant	Intron	Splice site	Infantile	0.03%	1	26.66	Pathogenic/Likely Pathogenic
c.854C>A	Splicing variant	Exon 11	Splice site	Infantile	0.03%	1	27.49	Undefined
40 kb incl. entire gene + SHPK	Large genomic deletion	Exons 3-12	Deletion	Infantile	0.03%	1	—	Undefined
651delTCAC	Large genomic deletion	Exon 9	Deletion	Infantile	0.03%	1	—	Undefined
ex 4 c.(61+1_62-1)_(140+1_140-1)	Large genomic deletion	Exon 4	Deletion	Infantile	0.03%	1	—	Undefined
incl ex. 6-10 (c.(225+1_226-1)_(852+1_853-1)del)	Large genomic deletion	Exons 6-10	Deletion	Infantile	0.03%	1	—	Undefined
c.27del	p.Phe9LeufsX6	Exon 3	Deletion	Infantile	0.03%	1	—	Pathogenic/Likely Pathogenic
c.36delT	p.Leu14*	Exon 3	Deletion	Infantile	0.03%	1	—	Undefined
c.225+1del4	Splicing variant	Exon 5	Splice site	Infantile	0.03%	1	—	Undefined
c.260_261delTT	p.Phe87Serfs*37	Exon 6	Deletion	Infantile	0.03%	1	—	Pathogenic
c.295_310del16	p.Val99Ilefs*14	Exon 6	Deletion	Infantile	0.03%	1	—	Undefined
c.400_402del	p.Tyr134del	Exon 7	Deletion	Infantile	0.03%	1	—	Undefined
c.462-27_426-3del	Splicing variant	Intron	Splice site	Juvenile	0.03%	1	—	Undefined
c.659_665delTCGTGCCA	p.Ile220Serfs*31	Exon 9	Deletion	Infantile	0.03%	1	—	Undefined
c.696_697del	p.Ser234Leufs*61	Exon 10	Deletion	Unclassified	0.03%	1	—	Undefined
c.790_791delCA	p.Gln264Valfs*31	Exon 10	Deletion	Infantile	0.03%	1	—	Pathogenic
c.1000delA	p.Thr334Profs*33	Exon 12	Deletion	Infantile	0.03%	1	—	Pathogenic/Likely Pathogenic
c.1036_1047del12	p.Asp346_Phe349del	Exon 12	Deletion	Infantile	0.03%	1	—	Conflicting
c.266dup	p.Thr90AspfsX35	Exon 6	Insertion	Unclassified	0.03%	1	—	Undefined
c.354_346insCACTT	p.Leu116Hisfs*2	Exon 7	Insertion	Infantile	0.03%	1	—	Undefined
c.587dupA	p.Asn196fs	Exon 9	Insertion	Infantile	0.03%	1	—	Likely Pathogenic
c.841dup	p.Ser310Alafs*55	Exon 10	Insertion	Infantile	0.03%	1	—	Pathogenic/Likely Pathogenic
c.927_928insG	p.Ser310Glnfs*55	Exon 11	Insertion	Infantile	0.03%	1	—	Undefined
c.1032delCinsTG	F345Cfs*19	Exon 12	Deletion	Infantile	0.03%	1	—	Undefined
c.1047_1048ins12	p.Phe349_Phe350insAspValGluPhe	Exon 12	Insertion	Infantile	0.03%	1	—	Undefined
c.-520T>C	Promoter region variant	Promoter	Promoter	Infantile	0.03%	1	—	Benign
c.-512 G>C	Promoter region variant	Promoter	Promoter	Unclassified	0.03%	1	—	Undefined
-303 insT	Promoter region variant	Promoter	Promoter	Ocular	0.03%	1	—	Undefined
c.3G>A	p.Met1Ile	Exon 3	Missense	Infantile	0.03%	1	34.00	Undefined
c.3G>C	p.Met1Ile	Exon 3	Missense	Infantile	0.03%	1	34.13	Undefined
c.116C>T	p.Ser39Leu	Exon 4	Missense	Infantile	0.03%	1	21.30	Conflicting
c.119C>G	p.Thr40Ser	Exon 4	Missense	Infantile	0.03%	1	18.06	Undefined
c.274C>T	p.Gln92*	Exon 6	Nonsense	Infantile	0.03%	1	37.02	Pathogenic
c.319A>C	p.Asn107His	Exon 6	Missense	Infantile	0.03%	1	20.24	Undefined
c.413G>A	p.Trp138*	Exon 7	Nonsense	Infantile	0.03%	1	41.07	Pathogenic
c.450G>A	p.Trp150*	Exon 7	Nonsense	Infantile	0.03%	1	38.93	Pathogenic
c.477C>G	p.Ser159Arg	Exon 8	Missense	Infantile	0.03%	1	26.53	Undefined
c.505G>T	p.Gly169Cys	Exon 8	Missense	Infantile	0.03%	1	29.73	Undefined
c.530A>C	p.Asn177Thr	Exon 8	Missense	Juvenile	0.03%	1	24.40	Undefined
c.544T>C	p.Trp182Arg	Exon 8	Missense	Infantile	0.03%	1	25.56	Likely Pathogenic
c.560A>G	p.Lys187Arg	Exon 8	Missense	Infantile	0.03%	1	22.61	Undefined
c.565C>T	p.Q189*	Exon 9	Nonsense	Infantile	0.03%	1	35.50	Pathogenic/Likely Pathogenic
c.629T>C	p.Leu210Pro	Exon 9	Missense	Juvenile	0.03%	1	27.15	Undefined
c.635C>T	p.Ala212Val	Exon 9	Missense	Ocular	0.03%	1	29.15	Pathogenic/Likely Pathogenic
c.647C>G	p.Thr216Arg	Exon 9	Missense	Infantile	0.03%	1	28.82	Likely Pathogenic
c.680A>T	p.Glu227Val	Exon 10	Missense	Infantile	0.03%	1	29.94	Undefined
c.695G>A	p.Arg232His	Exon 10	Missense	Ocular	0.03%	1	6.84	Conflicting
c.861G>A	p.Met287Ile	Exon 11	Missense	Infantile	0.03%	1	27.51	Uncertain Significance
c.878G>T	p.Ser293Ile	Exon 11	Missense	Infantile	0.03%	1	29.94	Undefined
c.893G>A	p.Ser298Asn	Exon 11	Missense	Infantile	0.03%	1	25.58	Uncertain Significance
c.925G>T	p.Gly309Cys	Exon 11	Missense	Infantile	0.03%	1	28.95	Undefined
c.926G>A	p.Gly309Asp	Exon 11	Missense	Infantile	0.03%	1	31.26	Uncertain Significance
c.926G>T	p.Gly309Val	Exon 11	Missense	Infantile	0.03%	1	31.25	Undefined
c.943C>T	p.Gln315*	Exon 11	Nonsense	Infantile	0.03%	1	42.97	Pathogenic
c.944A>G	p.Gln315Arg	Exon 11	Missense	Unclassified	0.03%	1	30.05	Likely Pathogenic
c.1036G>A	p.Asp346Asn	Exon 12	Missense	Unclassified	0.03%	1	27.28	Uncertain Significance
c.1084G>A	p.Gly362Arg	Exon 12	Missense	Infantile	0.03%	1	27.24	Undefined

Global Distribution of Published CTNS Alleles

Explore the global distribution of reported CTNS alleles. Click on a highlighted country to see which mutations have been reported there.

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1

756 alleles reported No data

🌍 Click on a highlighted country on the map above to see its reported CTNS mutations.

c.1015G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.1015G>A
Protein / Detail: p.Gly339Arg
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	30.30
SpliceAI max gain	0.01
SpliceAI max loss	0.01
REVEL	0.967
AlphaMissense	0.98
CADD Phred	31
SIFT	0
PolyPhen-2	0.996
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Greco, M. et al. Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr. Nephrol. 25, 2459-2467 (2010).
Rupar, C.A. et al. G339R mutation in the CTNS gene is a common cause of nephropathic cystinosis in the south western Ontario Amish Mennonite population. J. Med. Genet. 38, 615-616 (2001).
Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).
Sadeghipour, F. et al. Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. Hum. Genome Var. 4, 17038 (2017).
Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).
Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).
Kleta, R. et al. Long-term follow-up of well-treated nephropathic cystinosis patients. J. Pediatr. 145, 555-560 (2004).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Önenli-Mungan, N. et al. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk. J. Pediatr. 58, 362-370 (2016).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep. 6, 35395 (2016).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Shahkarami, S. et al. The first molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran. Nefrologia 33, 308-315 (2013).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Capalbo, A. et al. Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet. 15, e1008409 (2019).
Bitsori, M. et al. Slow progression of renal failure in a child with infantile cystinosis. CEN Case Rep. 7, 153-157 (2018).
Besouw, M.T.P. et al. Non-invasive measurements of atherosclerosis in adult cystinosis patients. J. Inherit. Metab. Dis. 34, 811-818 (2011).
Wamelink, M.M. et al. Sedoheptulokinase Deficiency Due to a 57-kbDeletion in Cystinosis Patients Causes UrinaryAccumulation of Sedoheptulose: Elucidationof theCARKL Gene. Hum. Mutat. 29, 532-536 (2008).
Kars, M.E. et al. The genetic structure of the Turkish population reveals high levels of variation and admixture. Proc. Natl. Acad. Sci. U.S.A. 118, e2026076118 (2021).
Servais, A. et al. Pregnancy in cystinosis patients with chronic kidney disease: A European case series. J. Inherit. Metab. Dis. 45, 963-968 (2022).
Reda, A. et al. Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis. J. Inherit. Metab. Dis. 44, 1393-1408 (2021).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Bertholet-Thomas, A. et al. Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment. Pediatr. Nephrol. 33, 1165-1172 (2018).
Wilmer, M.J. et al. Urinary Protein Excretion Pattern and Renal Expression of Megalin and Cubilin in Nephropathic Cystinosis. Am. J. Kidney Dis. 51, 893-903 (2008).
Ivanova, E.A. et al. Ca2+ signalling in human proximal tubular epithelial cells deficient for cystinosin. Cell Calcium 60, 282-287 (2016).
Ivanova, E.A. et al. Cystinosin deficiency causes podocyte damage and loss associated with increased cell motility. Kidney Int. 89, 1037-1048 (2016).

c.414G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.414G>A
Protein / Detail: p.Trp138*
Exon / Intron: Exon 7
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	46.07
SpliceAI max gain	0.39
SpliceAI max loss	0.32
CADD Phred	49

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
McGowan-Jordan, J. et al. Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation. Eur. J. Hum. Genet. 7, 671-678 (1999).
Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Thoene, J. et al. Mutations of CTNS causing intermediate cystinosis. Mol. Genet. Metab. 67, 283-293 (1999).
Barshop, B.A. et al. Hematopoietic Stem-Cell Gene Therapy for Cystinosis. N. Engl. J. Med. 394, 753-762 (2026).
Helip-Wooley, A. et al. Expression of CTNS alleles: subcellular localization and aminoglycoside correction in vitro. Mol. Genet. Metab. 75, 128-133 (2002).
Haverty, T. et al. Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX-02 in Patients With Nephropathic Cystinosis. J. Clin. Pharmacol. 61, 923-931 (2021).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Dohil, R. & Cabrera, B.L. Treatment of cystinosis with delayed-release cysteamine: 6-year follow-up. Pediatr. Nephrol. 28, 507-510 (2013).
Brasell, E.J. et al. The aminoglycoside geneticin permits translational readthrough of the CTNS W138X nonsense mutation in fibroblasts from patients with nephropathic cystinosis. Pediatr. Nephrol. 34, 873-881 (2019).
Sadjadi, R. et al. Clinical myopathy in patients with nephropathic cystinosis. Muscle Nerve 61, 74-80 (2020).

57 kb del.

CTNS large genomic deletion variant

Variant Summary

Nucleotide change: 57 kb del.
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 1-10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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CTNS Variant Map

References

Bendavid, C., Kleta, R., Long, R. et al. FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis. Hum. Genet. 115, 510-514 (2004).
Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Forestier, L. et al. Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay. Am. J. Hum. Genet. 65, 353-359 (1999).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).
Heil, S.G. et al. The molecular basis of Dutch infantile nephropathic cystinosis. Nephron. Nephron 89, 50-55 (2001).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).
McGowan-Jordan, J. et al. Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation. Eur. J. Hum. Genet. 7, 671-678 (1999).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).
Kalatzis, V. et al. Characterization of a putative founder mutation that accounts for the high incidence of cystinosis in Brittany. J. Am. Soc. Nephrol. 12, 2170-2174 (2001).
Taranta, A. et al. Analysis of CTNS gene transcripts in nephropathic cystinosis. Pediatr. Nephrol. 25, 1263-1267 (2010).
Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).
Kleta, R. et al. Long-term follow-up of well-treated nephropathic cystinosis patients. J. Pediatr. 145, 555-560 (2004).
Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Martín-Begué, N. et al. Intracranial Hypertension in Cystinosis Is a Challenge: Experience in a Children's Hospital. JIMD Rep. 35, 17-22 (2017).
Ferreira, F. & Vilarinho, L. CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population. Open J. Genet. 8, 91-100 (2018).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Cabrera-Serrano, M. et al. Cystinosis distal myopathy, novel clinical, pathological and genetic features. Neuromuscul. Disord. 27, 873-878 (2017).
Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep. 6, 35395 (2016).
Mallett, A.J. et al. Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders. Kidney Int. 92, 1493-1506 (2017).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Fleige, T. et al. Next generation sequencing as second-tier test in high-throughput newborn screening for nephropathic cystinosis. Eur. J. Hum. Genet. 28, 193-201 (2020).
Najafi, M. et al. A 57 kB Genomic Deletion Causing CTNS Loss of Function Contributes to the CTNS Mutational Spectrum in the Middle East. Front. Pediatr. 7, 89 (2019).
Pennesi, M. et al. A new mutation in two siblings with cystinosis presenting with Bartter syndrome. Pediatr. Nephrol. 20, 217-219 (2005).
Thoene, J. et al. Mutations of CTNS causing intermediate cystinosis. Mol. Genet. Metab. 67, 283-293 (1999).
Krall, P. et al. [Nephropatic cystinosis: report of one case]. Rev. Med. Chil. 146, 111-115 (2018).
Kleta, R. et al. CTNS mutations in African American patients with cystinosis. Mol. Genet. Metab. 74, 332-337 (2001).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Kowalczyk, M. et al. Ophthalmic Evaluation of Diagnosed Cases of Eye Cystinosis: A Tertiary Care Center’s Experience. Diagnostics 10, 911 (2020).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).
Anikster, Y. et al. Ocular Nonnephropathic Cystinosis: Clinical, Biochemical, and Molecular Correlations. Pediatr. Res. 47, 17-23 (2000).
Besouw, M.T.P. et al. Non-invasive measurements of atherosclerosis in adult cystinosis patients. J. Inherit. Metab. Dis. 34, 811-818 (2011).
Rohayem, J. et al. Testicular function in males with infantile nephropathic cystinosis. Hum. Reprod. 36, 1191-1204 (2021).
Lebre, A.-S. et al. Maternal uniparental heterodisomy of chromosome 17 in a patient with nephropathic cystinosis.. Eur. J. Hum. Genet. 17, 1019-1023 (2009).
Ueda, M. et al. Coronary Artery and Other Vascular Calcifications in Patients with Cystinosis after Kidney Transplantation. Clin. J. Am. Soc. Nephrol. 1, 555-562 (2006).
Barshop, B.A. et al. Hematopoietic Stem-Cell Gene Therapy for Cystinosis. N. Engl. J. Med. 394, 753-762 (2026).
Wamelink, M.M. et al. Sedoheptulokinase Deficiency Due to a 57-kbDeletion in Cystinosis Patients Causes UrinaryAccumulation of Sedoheptulose: Elucidationof theCARKL Gene. Hum. Mutat. 29, 532-536 (2008).
Freed, K.A. et al. The 57 kb deletion in cystinosis patients extends into TRPV1 causing dysregulation of transcription in peripheral blood mononuclear cells. J. Med. Genet. 48, 563-566 (2011).
Besouw, M.T.P. et al. Detailed studies of growth hormone secretion in cystinosis patients. Pediatr. Nephrol. 27, 2123-2127 (2012).
Joyce, E. et al. Value of Renal Biopsy in Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus. Pediatr. Dev. Pathol. 20, 72-75 (2017).
Alcántara-Ortigoza, M.A. et al. CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis. J. Pediatr. Genet. 2, 129-132 (2013).
Chiavérini, C. et al. In vivo reflectance confocal microscopy of the skin: A noninvasive means of assessing body cystine accumulation in infantile cystinosis. J. Am. Acad. Dermatol. 68, e111-e116 (2013).
Vercauteren, L. et al. Comparison of Scheimpflug Corneal Tomography and Anterior Segment Optical Coherence Tomography Measurements in Corneal Cystinosis: A Case Series. Eye Contact Lens 50, 321-328 (2024).
Helip-Wooley, A. et al. Expression of CTNS alleles: subcellular localization and aminoglycoside correction in vitro. Mol. Genet. Metab. 75, 128-133 (2002).
Verbitsky, M. et al. Genomic imbalances in pediatric patients with chronic kidney disease. J. Clin. Invest. 125, 2171-2178 (2015).
Hogan, G.J. et al. Validation of an Expanded Carrier Screen that Optimizes Sensitivity via Full-Exon Sequencing and Panel-wide Copy Number Variant Identification. Clin. Chem. 64, 1063-1073 (2018).
Sinopoli, H.J. et al. Failure to Thrive With Severe Hypokalemia Yields Cystinosis Diagnosis in a 19-Month-Old Female Child: A Case Report. Cureus 16, e63122 (2024).
Sendino Garví, E. et al. Bioengineered Cystinotic Kidney Tubules Recapitulate a Nephropathic Phenotype. Cells 11, 177 (2022).
Gama Marques, J. Schizophrenia Misdiagnosis after Capgras and Cotard Delusions in a Patient with Infantile Cystinosis, Cavum Septi Pellucidi, Cavum Vergae and Cavum Veli Interpositi. Behav. Sci. 13, 157 (2023).
Servais, A. et al. Pregnancy in cystinosis patients with chronic kidney disease: A European case series. J. Inherit. Metab. Dis. 45, 963-968 (2022).
Reda, A. et al. Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis. J. Inherit. Metab. Dis. 44, 1393-1408 (2021).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Veys, K.R.P. et al. Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis. J. Am. Soc. Nephrol. 31, 1092-1106 (2020).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).
Florenzano, P. et al. Nephropathic Cystinosis: A Distinct Form of CKD–Mineral and Bone Disorder that Provides Novel Insights into the Regulation of FGF23. J. Am. Soc. Nephrol. 31, 2184-2192 (2020).
Florenzano, P. et al. And Skeletal Consequences of Nephropathic Cystinosis. J. Bone Miner. Res. 33, 1870-1880 (2018).
Curie, A. et al. Neuropsychological and neuroanatomical phenotype in 17 patients with cystinosis. Orphanet J. Rare Dis. 15, 59 (2020).
Blackburn, J. & Ramakrishnan, R. Short stature: making a crystal clear diagnosis. J. Pediatr. Endocrinol. Metab. 32, 1187-1191 (2019).
Elmonem, M.A. et al. Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis: First human report. Am. J. Transplant. 18, 2823-2828 (2018).
Bertholet-Thomas, A. et al. Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment. Pediatr. Nephrol. 33, 1165-1172 (2018).
Besouw, M.T. et al. Management dilemmas in pediatric nephrology: Cystinosis. Pediatr. Nephrol. 30, 1349-1360 (2015).
Dohil, R. & Cabrera, B.L. Treatment of cystinosis with delayed-release cysteamine: 6-year follow-up. Pediatr. Nephrol. 28, 507-510 (2013).
Besouw, M.T.P. et al. Cysteamine Toxicity in Patients with Cystinosis. J. Pediatr. 159, 1004-1011 (2011).
Vaisbich, M.H. & Koch, V.H. Report of a Brazilian Multicenter Study on Nephropathic Cystinosis. Nephron Clin. Pract. 114, c12-c18 (2010).
Bockenhauer, D. et al. Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases. Nephron Physiol. 116, 23-29 (2010).
Wilmer, M.J. et al. Urinary Protein Excretion Pattern and Renal Expression of Megalin and Cubilin in Nephropathic Cystinosis. Am. J. Kidney Dis. 51, 893-903 (2008).
Gahl, W.A. et al. Nephropathic Cystinosis in Adults: Natural History and Effects of Oral Cysteamine Therapy. Ann. Intern. Med. 147, 242-250 (2007).
O'Brien, K. et al. Nodular Regenerative Hyperplasia and Severe Portal Hypertension in Cystinosis. Clin. Gastroenterol. Hepatol. 4, 387-394 (2006).
Levtchenko, E. & Monnens, L. Development of Fanconi syndrome during infancy in a patient with cystinosis. Acta Paediatr. 95, 379-380 (2006).
Sonies, B.C. et al. Swallowing dysfunction in 101 patients with nephropathic cystinosis: benefit of long-term cysteamine therapy. Medicine (Baltimore) 84, 137-146 (2005).
Medaer, L. et al. Residual Cystine Transport Activity for Specific Infantile and Juvenile CTNS Mutations in a PTEC-Based Addback Model. Cells 13, 646 (2024).
Veys, K. et al. Urine-Derived Kidney Progenitor Cells in Cystinosis. Cells 11, 1245 (2022).
Wilmer, M.J. et al. Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim. Biophys. Acta 1812, 643-651 (2011).
Rega, L.R. et al. Activation of the transcription factor EB rescues lysosomal abnormalities in cystinotic kidney cells. Kidney Int. 89, 862-873 (2016).
Brasell, E.J. et al. The aminoglycoside geneticin permits translational readthrough of the CTNS W138X nonsense mutation in fibroblasts from patients with nephropathic cystinosis. Pediatr. Nephrol. 34, 873-881 (2019).
Ivanova, E.A. et al. Ca2+ signalling in human proximal tubular epithelial cells deficient for cystinosin. Cell Calcium 60, 282-287 (2016).
Ivanova, E.A. et al. Cystinosin deficiency causes podocyte damage and loss associated with increased cell motility. Kidney Int. 89, 1037-1048 (2016).
Sadjadi, R. et al. Clinical myopathy in patients with nephropathic cystinosis. Muscle Nerve 61, 74-80 (2020).

c.681G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.681G>A
Protein / Detail: Splicing variant
Exon / Intron: Exon 9
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	25.83
SpliceAI max gain	0.42
SpliceAI max loss	0.16
CADD Phred	23.3

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).
Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).
Sadeghipour, F. et al. Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. Hum. Genome Var. 4, 17038 (2017).
Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).
Önenli-Mungan, N. et al. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk. J. Pediatr. 58, 362-370 (2016).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Shahkarami, S. et al. The first molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran. Nefrologia 33, 308-315 (2013).
Doğan, M. et al. Cystinosis in Eastern Turkey. J. Pediatr. Endocrinol. Metab. 29, 965-969 (2016).
Wamelink, M.M. et al. Sedoheptulokinase Deficiency Due to a 57-kbDeletion in Cystinosis Patients Causes UrinaryAccumulation of Sedoheptulose: Elucidationof theCARKL Gene. Hum. Mutat. 29, 532-536 (2008).
Kars, M.E. et al. The genetic structure of the Turkish population reveals high levels of variation and admixture. Proc. Natl. Acad. Sci. U.S.A. 118, e2026076118 (2021).
Wilmer, M.J. et al. Urinary Protein Excretion Pattern and Renal Expression of Megalin and Cubilin in Nephropathic Cystinosis. Am. J. Kidney Dis. 51, 893-903 (2008).

c.198_218del21

CTNS in-frame deletion variant

Variant Summary

Nucleotide change: c.198_218del21
Protein / Detail: p.Ile67_Pro73del
Exon / Intron: Exon 5
Variant Type: Deletion
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Heil, S.G. et al. The molecular basis of Dutch infantile nephropathic cystinosis. Nephron. Nephron 89, 50-55 (2001).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Cabrera-Serrano, M. et al. Cystinosis distal myopathy, novel clinical, pathological and genetic features. Neuromuscul. Disord. 27, 873-878 (2017).
Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep. 6, 35395 (2016).
Braun, D.A. et al. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity. Kidney Int. 89, 468-475 (2016).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).
Besouw, M.T.P. et al. Non-invasive measurements of atherosclerosis in adult cystinosis patients. J. Inherit. Metab. Dis. 34, 811-818 (2011).
Midgley, J.P. et al. Natural history of adolescent-onset cystinosis. Pediatr. Nephrol. 26, 1335-1337 (2011).
Besouw, M.T. et al. Neurocognitive functioning in school-aged cystinosis patients. J. Inherit. Metab. Dis. 33, 787-793 (2010).
Wamelink, M.M. et al. Sedoheptulokinase Deficiency Due to a 57-kbDeletion in Cystinosis Patients Causes UrinaryAccumulation of Sedoheptulose: Elucidationof theCARKL Gene. Hum. Mutat. 29, 532-536 (2008).
Besouw, M.T.P. et al. Detailed studies of growth hormone secretion in cystinosis patients. Pediatr. Nephrol. 27, 2123-2127 (2012).
Reda, A. et al. Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis. J. Inherit. Metab. Dis. 44, 1393-1408 (2021).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Wilmer, M.J. et al. Urinary Protein Excretion Pattern and Renal Expression of Megalin and Cubilin in Nephropathic Cystinosis. Am. J. Kidney Dis. 51, 893-903 (2008).
Besouw, M.T. et al. Growth hormone producing prolactinoma in juvenile cystinosis: a simple coincidence?. Pediatr. Nephrol. 23, 307-310 (2008).
Veys, K. et al. Urine-Derived Kidney Progenitor Cells in Cystinosis. Cells 11, 1245 (2022).
Ivanova, E.A. et al. Cystinosin deficiency causes podocyte damage and loss associated with increased cell motility. Kidney Int. 89, 1037-1048 (2016).
Sadjadi, R. et al. Clinical myopathy in patients with nephropathic cystinosis. Muscle Nerve 61, 74-80 (2020).

c.681+1G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.681+1G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	34.26
SpliceAI max gain	0.56
SpliceAI max loss	1
CADD Phred	35

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Greco, M. et al. Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr. Nephrol. 25, 2459-2467 (2010).
Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.829dupA

CTNS frameshift variant

Variant Summary

Nucleotide change: c.829dupA
Protein / Detail: p.Thr277Asnfs*19
Exon / Intron: Exon 10
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Sahli, C. et al. Molecular characterization of cystinosis patients: predominance of the CTNS c.829dup mutation in Center Tunisia patients: predominance of the CTNS c.829dup mutation in Center of Tunisia. BMC Genom. Data 27, 25 (2026).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Chkioua, L. et al. Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis. Diagn. Pathol. 17, 44 (2022).
Jaradat, S. et al. Molecular analysis of the CTNS gene in Jordanian families with nephropathic cystinosis. Nefrologia 35, 547-553 (2015).
Daga, A. et al. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int. 93, 204-213 (2018).
Besouw, M.T.P. et al. Detailed studies of growth hormone secretion in cystinosis patients. Pediatr. Nephrol. 27, 2123-2127 (2012).

c.926dupG

CTNS frameshift variant

Variant Summary

Nucleotide change: c.926dupG
Protein / Detail: p.Ser310Glnfs*55
Exon / Intron: Exon 11
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).
Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep. 6, 35395 (2016).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Besouw, M.T.P. et al. Non-invasive measurements of atherosclerosis in adult cystinosis patients. J. Inherit. Metab. Dis. 34, 811-818 (2011).
Rohayem, J. et al. Testicular function in males with infantile nephropathic cystinosis. Hum. Reprod. 36, 1191-1204 (2021).
Wamelink, M.M. et al. Sedoheptulokinase Deficiency Due to a 57-kbDeletion in Cystinosis Patients Causes UrinaryAccumulation of Sedoheptulose: Elucidationof theCARKL Gene. Hum. Mutat. 29, 532-536 (2008).
Besouw, M.T.P. et al. Detailed studies of growth hormone secretion in cystinosis patients. Pediatr. Nephrol. 27, 2123-2127 (2012).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Elmonem, M.A. et al. Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis: First human report. Am. J. Transplant. 18, 2823-2828 (2018).
Bertholet-Thomas, A. et al. Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment. Pediatr. Nephrol. 33, 1165-1172 (2018).
Besouw, M.T. et al. Pharmacokinetics of cysteamine in a cystinosis patient treated with hemodialysis. Pediatr. Nephrol. 26, 639-640 (2011).
Wilmer, M.J. et al. Urinary Protein Excretion Pattern and Renal Expression of Megalin and Cubilin in Nephropathic Cystinosis. Am. J. Kidney Dis. 51, 893-903 (2008).
Veys, K. et al. Urine-Derived Kidney Progenitor Cells in Cystinosis. Cells 11, 1245 (2022).
Ivanova, E.A. et al. Cystinosin deficiency causes podocyte damage and loss associated with increased cell motility. Kidney Int. 89, 1037-1048 (2016).

c.971-12G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.971-12G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	25.92
SpliceAI max gain	0.99
SpliceAI max loss	0.87
CADD Phred	24.1

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Sadeghipour, F. et al. Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. Hum. Genome Var. 4, 17038 (2017).
Owen, E.P. et al. Common mutation causes cystinosis in the majority of black South African patients. Pediatr. Nephrol. 30, 595-601 (2015).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Robertson, G. et al. A Successful Adolescent Pregnancy in a Patient With Cystinosis and CKD Not Yet on Kidney Replacement Therapy. Kidney Int. Rep. 7, 1711-1715 (2022).
Marik, B. et al. Genetic and clinical profile of patients with hypophosphatemic rickets. Eur. J. Med. Genet. 65, 104540 (2022).
Al-Haggar, M. et al. A Recent Experience in an Egyptian Medical Center: Strategies for the Clinical and Genetic Diagnoses of Nephropathic Cystinosis. Br. J. Med. Res. 3, 1918-1928 (2013).
Al-Haggar, M. et al. Novel truncating mutation in the CTNS gene in an Egyptian family with cases of infantile nephropathic cystinosis and congenital heart malformations. Middle East J. Med. Genet. 1, 71-75 (2012).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.922G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.922G>A
Protein / Detail: p.Gly308Arg
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	31.93
SpliceAI max gain	0.01
SpliceAI max loss	0.01
REVEL	0.991
AlphaMissense	0.978
CADD Phred	34
SIFT	0
PolyPhen-2	1
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).
Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).
Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).
Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Chkioua, L. et al. Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene. Meta Gene 5, 144-149 (2015).
Chkioua, L. et al. Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis. Diagn. Pathol. 17, 44 (2022).
Wang, X. et al. Cystinosis induced by CTNS gene mutation: a rare disease study. Zhongguo Dang Dai Er Ke Za Zhi 23, 1276-1281 (2021).
Chiavérini, C. et al. In vivo reflectance confocal microscopy of the skin: A noninvasive means of assessing body cystine accumulation in infantile cystinosis. J. Am. Acad. Dermatol. 68, e111-e116 (2013).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).
Sadjadi, R. et al. Clinical myopathy in patients with nephropathic cystinosis. Muscle Nerve 61, 74-80 (2020).

c.451A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.451A>G
Protein / Detail: p.Arg151Gly
Exon / Intron: Exon 7
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	25.55
SpliceAI max gain	0.19
SpliceAI max loss	0.33
REVEL	0.951
AlphaMissense	0.21
CADD Phred	32
SIFT	0
PolyPhen-2	0.836
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Önenli-Mungan, N. et al. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk. J. Pediatr. 58, 362-370 (2016).
Schiefer, J. et al. Unrecognized juvenile nephropathic cystinosis. Kidney Int. 94, 1027 (2018).

c.646dupA

CTNS frameshift variant

Variant Summary

Nucleotide change: c.646dupA
Protein / Detail: p.Thr216Asnfs*12
Exon / Intron: Exon 9
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Martín-Begué, N. et al. Intracranial Hypertension in Cystinosis Is a Challenge: Experience in a Children's Hospital. JIMD Rep. 35, 17-22 (2017).
Capalbo, A. et al. Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet. 15, e1008409 (2019).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).
Alcántara-Ortigoza, M.A. et al. CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis. J. Pediatr. Genet. 2, 129-132 (2013).

c.422C>T

CTNS missense variant

Variant Summary

Nucleotide change: c.422C>T
Protein / Detail: p.Ser141Phe
Exon / Intron: Exon 7
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	31.31
SpliceAI max gain	0.08
SpliceAI max loss	0.11
REVEL	0.942
AlphaMissense	0.969
CADD Phred	33
SIFT	0
PolyPhen-2	1
Grantham distance	155
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).
Owen, E.P. et al. Common mutation causes cystinosis in the majority of black South African patients. Pediatr. Nephrol. 30, 595-601 (2015).
Deshpande, A.A. et al. Molecular Analysis of the CTNS Gene in Indians with Nephropathic Cystinosis. Indian J. Pediatr. 84, 240-241 (2017).
Sinha, R. et al. Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study. Pediatr. Nephrol. 37, 1811-1836 (2022).

c.140+1G>T

CTNS splice site variant

Variant Summary

Nucleotide change: c.140+1G>T
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	34.62
SpliceAI max gain	0
SpliceAI max loss	1
CADD Phred	27.9

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Kars, M.E. et al. The genetic structure of the Turkish population reveals high levels of variation and admixture. Proc. Natl. Acad. Sci. U.S.A. 118, e2026076118 (2021).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).
Bertholet-Thomas, A. et al. Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment. Pediatr. Nephrol. 33, 1165-1172 (2018).

c.518A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.518A>G
Protein / Detail: p.Tyr173Cys
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	25.17
SpliceAI max gain	0
SpliceAI max loss	0.01
REVEL	0.98
AlphaMissense	0.711
CADD Phred	29.6
SIFT	0
PolyPhen-2	1
Grantham distance	194
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Kozina, A.A. et al. Atypical onset of nephropathic infantile cystinosis in a Russian patient with rare CTNS mutation. Clin. Case Rep. 6, 1871-1876 (2018).
Blackburn, J. & Ramakrishnan, R. Short stature: making a crystal clear diagnosis. J. Pediatr. Endocrinol. Metab. 32, 1187-1191 (2019).

c.771_793del23

CTNS frameshift variant

Variant Summary

Nucleotide change: c.771_793del23
Protein / Detail: p.Gly258Serfs*30
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Chkioua, L. et al. Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene. Meta Gene 5, 144-149 (2015).
Chkioua, L. et al. Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis. Diagn. Pathol. 17, 44 (2022).
Monies, D. et al. Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population. Am. J. Hum. Genet. 104, 1182-1201 (2019).
Cheema, H. et al. Genomic testing in 1019 individuals from 349 Pakistani families results in high diagnostic yield and clinical utility. NPJ Genom. Med. 5, 44 (2020).
Hogan, G.J. et al. Validation of an Expanded Carrier Screen that Optimizes Sensitivity via Full-Exon Sequencing and Panel-wide Copy Number Variant Identification. Clin. Chem. 64, 1063-1073 (2018).

c.696dupC

CTNS frameshift variant

Variant Summary

Nucleotide change: c.696dupC
Protein / Detail: p.Val233Argfs*63
Exon / Intron: Exon 10
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
McGowan-Jordan, J. et al. Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation. Eur. J. Hum. Genet. 7, 671-678 (1999).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep. 6, 35395 (2016).
Capalbo, A. et al. Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet. 15, e1008409 (2019).
Barshop, B.A. et al. Hematopoietic Stem-Cell Gene Therapy for Cystinosis. N. Engl. J. Med. 394, 753-762 (2026).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Wilmer, M.J. et al. Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim. Biophys. Acta 1812, 643-651 (2011).
Brasell, E.J. et al. The aminoglycoside geneticin permits translational readthrough of the CTNS W138X nonsense mutation in fibroblasts from patients with nephropathic cystinosis. Pediatr. Nephrol. 34, 873-881 (2019).

c.283G>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.283G>T
Protein / Detail: p.Gly95*
Exon / Intron: Exon 6
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	45.84
SpliceAI max gain	0.01
SpliceAI max loss	0.3
CADD Phred	44

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.473T>C

CTNS missense variant

Variant Summary

Nucleotide change: c.473T>C
Protein / Detail: p.Leu158Pro
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	27.54
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.987
AlphaMissense	0.986
CADD Phred	26.7
SIFT	0
PolyPhen-2	0.999
Grantham distance	98
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
McGowan-Jordan, J. et al. Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation. Eur. J. Hum. Genet. 7, 671-678 (1999).
Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Barshop, B.A. et al. Hematopoietic Stem-Cell Gene Therapy for Cystinosis. N. Engl. J. Med. 394, 753-762 (2026).
Chiavérini, C. et al. In vivo reflectance confocal microscopy of the skin: A noninvasive means of assessing body cystine accumulation in infantile cystinosis. J. Am. Acad. Dermatol. 68, e111-e116 (2013).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.809_811delCCT

CTNS deletion variant

Variant Summary

Nucleotide change: c.809_811delCCT
Protein / Detail: p.Ser270del
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).
Warejko, J.K. et al. Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome. Clin. J. Am. Soc. Nephrol. 13, 53-62 (2018).
Vivante, A. et al. Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract. J. Am. Soc. Nephrol. 28, 69-75 (2017).
Tang, S. et al. An Indian Boy with Nephropathic Cystinosis: A Case Report and Molecular Analysis of CTNS Mutation. Genet. Test. Mol. Biomarkers 13, 435-438 (2009).
Alcántara-Ortigoza, M.A. et al. CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis. J. Pediatr. Genet. 2, 129-132 (2013).

c.1013T>G

CTNS missense variant

Variant Summary

Nucleotide change: c.1013T>G
Protein / Detail: p.Leu338Arg
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	27.18
SpliceAI max gain	0.01
SpliceAI max loss	0
REVEL	0.983
AlphaMissense	0.953
CADD Phred	27.3
SIFT	0.01
PolyPhen-2	0.999
BLOSUM62	-2

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).

c.141-22A>G

CTNS splice site variant

Variant Summary

Nucleotide change: c.141-22A>G
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	26.24
SpliceAI max gain	0
SpliceAI max loss	0.43
CADD Phred	15.14

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.2T>C

CTNS missense variant

Variant Summary

Nucleotide change: c.2T>C
Protein / Detail: p.Met1Thr
Exon / Intron: Exon 3
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	27.44
SpliceAI max gain	0.05
SpliceAI max loss	0
CADD Phred	19.74
SIFT	0
PolyPhen-2	0.356
Grantham distance	81
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This variant affects the initiator start codon (Met1) of the CTNS coding sequence. Since translation of the CTNS open reading frame normally begins at this codon, the predicted outcome is that no CTNS amino acid sequence is translated from this transcript at all (barring the use of an alternative, non-canonical downstream start codon, which is not modeled here). Because there is no resulting CTNS protein product to depict, no 3D structure prediction is shown for this variant.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).

c.696_697dupCG

CTNS insertion variant

Variant Summary

Nucleotide change: c.696_697dupCG
Protein / Detail: p.Val233Alafs*21
Exon / Intron: Exon 10
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Joyce, E. et al. Value of Renal Biopsy in Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus. Pediatr. Dev. Pathol. 20, 72-75 (2017).

c.416C>T

CTNS missense variant

Variant Summary

Nucleotide change: c.416C>T
Protein / Detail: p.Ser139Phe
Exon / Intron: Exon 7
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	31.42
SpliceAI max gain	0.05
SpliceAI max loss	0.05
REVEL	0.958
AlphaMissense	0.965
CADD Phred	31
SIFT	0
PolyPhen-2	0.988
Grantham distance	155
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Ferreira, F. & Vilarinho, L. CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population. Open J. Genet. 8, 91-100 (2018).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).
Sousa-Neves, F. et al. Ocular manifestations of intermediate cystinosis: To treat or not to treat?. Eur. J. Ophthalmol. 30, NP7-NP10 (2020).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).
Sadjadi, R. et al. Clinical myopathy in patients with nephropathic cystinosis. Muscle Nerve 61, 74-80 (2020).

c.559_561+24del27

CTNS deletion variant

Variant Summary

Nucleotide change: c.559_561+24del27
Protein / Detail: p.Lys187del
Exon / Intron: Exon 8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Kalatzis, V. et al. Characterization of a putative founder mutation that accounts for the high incidence of cystinosis in Brittany. J. Am. Soc. Nephrol. 12, 2170-2174 (2001).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Browning, A.C. et al. A case of ocular cystinosis associated with two potentially severe CTNS mutations. Ophthalmic Genet. 40, 157-160 (2019).
Marik, B. et al. Genetic and clinical profile of patients with hypophosphatemic rickets. Eur. J. Med. Genet. 65, 104540 (2022).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.834_842delGGTCAAGTA

CTNS deletion variant

Variant Summary

Nucleotide change: c.834_842delGGTCAAGTA
Protein / Detail: p.Val279_Tyr281del
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Önenli-Mungan, N. et al. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk. J. Pediatr. 58, 362-370 (2016).

ex. 4-5

CTNS deletion variant

Variant Summary

Nucleotide change: ex. 4-5
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 4-5
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Ouhenach, M. et al. Application of next generation sequencing in genetic counseling a case of a couple at risk of cystinosis. BMC Med. Genet. 21, 240 (2020).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.613G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.613G>A
Protein / Detail: p.Asp205Asn
Exon / Intron: Exon 9
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	29.88
SpliceAI max gain	0.01
SpliceAI max loss	0.01
REVEL	0.866
AlphaMissense	0.935
CADD Phred	27.9
SIFT	0
PolyPhen-2	0.974
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Sadeghipour, F. et al. Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. Hum. Genome Var. 4, 17038 (2017).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Tucker, T. et al. A co-occurrence of osteogenesis imperfecta type VI and cystinosis. Am. J. Med. Genet. A 158A, 1422-1426 (2012).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.969C>G

CTNS missense variant

Variant Summary

Nucleotide change: c.969C>G
Protein / Detail: p.Asn323Lys
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	16.70
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.612
AlphaMissense	0.779
CADD Phred	17
SIFT	0
PolyPhen-2	0.818
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Yeetong, P. et al. Two novel CTNS mutations in cystinosis patients in Thailand.. Gene 499, 323-325 (2012).
Li, X.-Q. et al. The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population. J. Pediatr. Endocrinol. Metab. 32, 375-382 (2019).
Thoene, J. et al. Mutations of CTNS causing intermediate cystinosis. Mol. Genet. Metab. 67, 283-293 (1999).

~13 kb incl. ex. 1-3 3'brk E3I3+183

CTNS deletion variant

Variant Summary

Nucleotide change: ~13 kb incl. ex. 1-3 3'brk E3I3+183
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 1-3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Forestier, L. et al. Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay. Am. J. Hum. Genet. 65, 353-359 (1999).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.323delA

CTNS deletion variant

Variant Summary

Nucleotide change: c.323delA
Protein / Detail: p.Gln108Argfs*10
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).
Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).
Gholami Yarahmadi, S. et al. Cystinosis and two rare mutations in CTNS gene: two case reports. J. Med. Case Rep. 16, 181 (2022).

c.665A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.665A>G
Protein / Detail: p.Gln222Arg
Exon / Intron: Exon 10
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	25.99
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.959
AlphaMissense	0.925
CADD Phred	24.8
SIFT	0
PolyPhen-2	0.939
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).
Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep. 6, 35395 (2016).
Besouw, M.T.P. et al. Non-invasive measurements of atherosclerosis in adult cystinosis patients. J. Inherit. Metab. Dis. 34, 811-818 (2011).
Wilmer, M.J. et al. Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim. Biophys. Acta 1812, 643-651 (2011).

c.141-24T>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.141-24T>C
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	24.10
SpliceAI max gain	0
SpliceAI max loss	0.21
CADD Phred	19.99

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Taranta, A. et al. Analysis of CTNS gene transcripts in nephropathic cystinosis. Pediatr. Nephrol. 25, 1263-1267 (2010).
Veys, K.R. et al. First Successful Conception Induced by a Male Cystinosis Patient. JIMD Rep. 38, 1-6 (2018).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Reda, A. et al. Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis. J. Inherit. Metab. Dis. 44, 1393-1408 (2021).
Wilmer, M.J. et al. Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim. Biophys. Acta 1812, 643-651 (2011).

c.225+3A>T

CTNS splice site variant

Variant Summary

Nucleotide change: c.225+3A>T
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	29.67
SpliceAI max gain	0
SpliceAI max loss	0.95
CADD Phred	9.921

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).

c.682-1G>T

CTNS splice site variant

Variant Summary

Nucleotide change: c.682-1G>T
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	34.16
SpliceAI max gain	0.55
SpliceAI max loss	0.95
CADD Phred	32

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Martín-Begué, N. et al. Intracranial Hypertension in Cystinosis Is a Challenge: Experience in a Children's Hospital. JIMD Rep. 35, 17-22 (2017).
Vercauteren, L. et al. Comparison of Scheimpflug Corneal Tomography and Anterior Segment Optical Coherence Tomography Measurements in Corneal Cystinosis: A Case Series. Eye Contact Lens 50, 321-328 (2024).

c.433C>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.433C>T
Protein / Detail: p.Gln145*
Exon / Intron: Exon 7
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	44.90
SpliceAI max gain	0.15
SpliceAI max loss	0.64
CADD Phred	50

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).
Sadeghipour, F. et al. Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. Hum. Genome Var. 4, 17038 (2017).

c.314_317delACTC

CTNS deletion variant

Variant Summary

Nucleotide change: c.314_317delACTC
Protein / Detail: p.His105Profs*12
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).

c.922insG

CTNS insertion variant

Variant Summary

Nucleotide change: c.922insG
Protein / Detail: p.S310Qfs54
Exon / Intron: Exon 11
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Heil, S.G. et al. The molecular basis of Dutch infantile nephropathic cystinosis. Nephron. Nephron 89, 50-55 (2001).
Wamelink, M.M. et al. Sedoheptulokinase Deficiency Due to a 57-kbDeletion in Cystinosis Patients Causes UrinaryAccumulation of Sedoheptulose: Elucidationof theCARKL Gene. Hum. Mutat. 29, 532-536 (2008).
Reda, A. et al. Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis. J. Inherit. Metab. Dis. 44, 1393-1408 (2021).
Wilmer, M.J. et al. Urinary Protein Excretion Pattern and Renal Expression of Megalin and Cubilin in Nephropathic Cystinosis. Am. J. Kidney Dis. 51, 893-903 (2008).

c.261T>A

CTNS missense variant

Variant Summary

Nucleotide change: c.261T>A
Protein / Detail: p.Phe87Leu
Exon / Intron: Exon 6
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	24.54
SpliceAI max gain	0
SpliceAI max loss	0.03
REVEL	0.609
AlphaMissense	0.86
CADD Phred	17.45
SIFT	0.05
PolyPhen-2	0.054
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.382C>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.382C>T
Protein / Detail: p.Gln128*
Exon / Intron: Exon 7
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	42.39
SpliceAI max gain	0
SpliceAI max loss	0.5
CADD Phred	41

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Ferreira, F. & Vilarinho, L. CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population. Open J. Genet. 8, 91-100 (2018).
Correia-Costa, G.R. et al. Dual Molecular Diagnoses of Recessive Disorders in a Child from Consanguineous Parents: Case Report and Literature Review. Genes 13, 2377 (2022).
Alcántara-Ortigoza, M.A. et al. CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis. J. Pediatr. Genet. 2, 129-132 (2013).

c.61+5G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.61+5G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	37.40
SpliceAI max gain	0
SpliceAI max loss	0.93
CADD Phred	22.2

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.699_700delGT

CTNS deletion variant

Variant Summary

Nucleotide change: c.699_700delGT
Protein / Detail: p.Ser234Leufs*61
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Guzzo, I. et al. Radiotherapy-induced hyperthyroidism in a cystinotic kidney transplant patient with Hodgkin lymphoma. Pediatr. Transplant. 15, e56-e59 (2011).

c.960delC

CTNS deletion variant

Variant Summary

Nucleotide change: c.960delC
Protein / Detail: p.Tyr321Thrfs*8
Exon / Intron: Exon 11
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.589G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.589G>A
Protein / Detail: p.Gly197Arg
Exon / Intron: Exon 9
Variant Type: Missense
Clinical Manifestation: Ocular
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	33.42
SpliceAI max gain	0.86
SpliceAI max loss	0.1
REVEL	0.932
AlphaMissense	0.695
CADD Phred	36
SIFT	0
PolyPhen-2	0.255
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Kleta, R. et al. CTNS mutations in African American patients with cystinosis. Mol. Genet. Metab. 74, 332-337 (2001).
Rasouly, H.M. et al. The Burden of Candidate Pathogenic Variants for Kidney and Genitourinary Disorders Emerging From Exome Sequencing. Ann. Intern. Med. 170, 11-21 (2019).
Chau, J.F.T. et al. Comprehensive analysis of recessive carrier status using exome and genome sequencing data in 1543 Southern Chinese. NPJ Genom. Med. 7, 23 (2022).
Anikster, Y. et al. Ocular Nonnephropathic Cystinosis: Clinical, Biochemical, and Molecular Correlations. Pediatr. Res. 47, 17-23 (2000).
Kars, M.E. et al. The genetic structure of the Turkish population reveals high levels of variation and admixture. Proc. Natl. Acad. Sci. U.S.A. 118, e2026076118 (2021).

c.357_360del

CTNS deletion variant

Variant Summary

Nucleotide change: c.357_360del
Protein / Detail: p.Ser120AlafsX6
Exon / Intron: Exon 7
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

-295 G>C

CTNS promoter variant

Variant Summary

Nucleotide change: -295 G>C
Protein / Detail: Promoter region variant
Exon / Intron: Promoter
Variant Type: Promoter
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

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Explore CTNS Gene

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CTNS Variant Map

References

Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Phornphutkul, C. et al. The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region. Am. J. Hum. Genet. 69, 712-721 (2001).

c.923G>T

CTNS missense variant

Variant Summary

Nucleotide change: c.923G>T
Protein / Detail: p.Gly308Val
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	31.30
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.991
AlphaMissense	0.968
CADD Phred	32
SIFT	0
PolyPhen-2	1
Grantham distance	109
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).

c.461+1G>T

CTNS splice site variant

Variant Summary

Nucleotide change: c.461+1G>T
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	31.65
SpliceAI max gain	0.12
SpliceAI max loss	0.95
CADD Phred	34

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.970+2T>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.970+2T>C
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	33.19
SpliceAI max gain	0
SpliceAI max loss	0.94
CADD Phred	31

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Thoene, J. et al. Mutations of CTNS causing intermediate cystinosis. Mol. Genet. Metab. 67, 283-293 (1999).
Helip-Wooley, A. et al. Expression of CTNS alleles: subcellular localization and aminoglycoside correction in vitro. Mol. Genet. Metab. 75, 128-133 (2002).

>1.7kb incl promoter & non-coding ex. 1-2

CTNS deletion variant

Variant Summary

Nucleotide change: >1.7kb incl promoter & non-coding ex. 1-2
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 1-2
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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CTNS Variant Map

References

Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Kiehntopf, M. et al. A homemade MLPA assay detects known CTNS mutations and identifies a novel deletion in a previously unresolved cystinosis family. Gene 495, 89-92 (2012).

c.206_210delTCCTT

CTNS deletion variant

Variant Summary

Nucleotide change: c.206_210delTCCTT
Protein / Detail: p.Ile69Argfs*5
Exon / Intron: Exon 5
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Anikster, Y. et al. Ocular Nonnephropathic Cystinosis: Clinical, Biochemical, and Molecular Correlations. Pediatr. Res. 47, 17-23 (2000).
Helip-Wooley, A. et al. Expression of CTNS alleles: subcellular localization and aminoglycoside correction in vitro. Mol. Genet. Metab. 75, 128-133 (2002).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.257_258delCT

CTNS deletion variant

Variant Summary

Nucleotide change: c.257_258delCT
Protein / Detail: p.Ser86Phefs*38
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).
Gholami Yarahmadi, S. et al. Cystinosis and two rare mutations in CTNS gene: two case reports. J. Med. Case Rep. 16, 181 (2022).

c.295_298delGTTT

CTNS deletion variant

Variant Summary

Nucleotide change: c.295_298delGTTT
Protein / Detail: p.Val99Ilefs*18
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Barshop, B.A. et al. Hematopoietic Stem-Cell Gene Therapy for Cystinosis. N. Engl. J. Med. 394, 753-762 (2026).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.518_519delAC

CTNS deletion variant

Variant Summary

Nucleotide change: c.518_519delAC
Protein / Detail: p.Tyr173*
Exon / Intron: Exon 8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Domingo-Gallego, A. et al. Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players. Nephrol. Dial. Transplant. 37, 687-696 (2022).
Chiavérini, C. et al. In vivo reflectance confocal microscopy of the skin: A noninvasive means of assessing body cystine accumulation in infantile cystinosis. J. Am. Acad. Dermatol. 68, e111-e116 (2013).

c.519_520delCA

CTNS deletion variant

Variant Summary

Nucleotide change: c.519_520delCA
Protein / Detail: p.Tyr173*
Exon / Intron: Exon 8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Ivanova, E.A. et al. Ca2+ signalling in human proximal tubular epithelial cells deficient for cystinosin. Cell Calcium 60, 282-287 (2016).

c.992delG

CTNS deletion variant

Variant Summary

Nucleotide change: c.992delG
Protein / Detail: p.Gly331Glufs*36
Exon / Intron: Exon 12
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.140+2T>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.140+2T>C
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	33.14
SpliceAI max gain	0
SpliceAI max loss	0.96
CADD Phred	23.7

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.569_577delTTCTCCTCA

CTNS deletion variant

Variant Summary

Nucleotide change: c.569_577delTTCTCCTCA
Protein / Detail: p.Phe190*
Exon / Intron: Exon 9
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).

c.741delC

CTNS deletion variant

Variant Summary

Nucleotide change: c.741delC
Protein / Detail: p.Phe247Leufs*6
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.530A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.530A>G
Protein / Detail: p.Asn177Ser
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	22.18
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.869
AlphaMissense	0.244
CADD Phred	25.8
SIFT	0
PolyPhen-2	0.956
Grantham distance	46
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).
Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).
Bondue, T. et al. The Pitfall of White Blood Cell Cystine Measurement to Diagnose Juvenile Cystinosis. Int. J. Mol. Sci. 24, 1253 (2023).

c.734G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.734G>A
Protein / Detail: p.Trp245*
Exon / Intron: Exon 10
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	36.72
SpliceAI max gain	0.03
SpliceAI max loss	0.05
CADD Phred	40

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).
Al-Haggar, M. et al. A Recent Experience in an Egyptian Medical Center: Strategies for the Clinical and Genetic Diagnoses of Nephropathic Cystinosis. Br. J. Med. Res. 3, 1918-1928 (2013).
Al-Haggar, M. et al. Novel truncating mutation in the CTNS gene in an Egyptian family with cases of infantile nephropathic cystinosis and congenital heart malformations. Middle East J. Med. Genet. 1, 71-75 (2012).

c.785G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.785G>A
Protein / Detail: p.Trp262*
Exon / Intron: Exon 10
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	40.18
SpliceAI max gain	0.03
SpliceAI max loss	0.09
CADD Phred	51

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.969C>A

CTNS missense variant

Variant Summary

Nucleotide change: c.969C>A
Protein / Detail: p.Asn323Lys
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	23.38
SpliceAI max gain	0.03
SpliceAI max loss	0
REVEL	0.612
AlphaMissense	0.779
CADD Phred	16.21
SIFT	0
PolyPhen-2	0.818
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.1001C>A

CTNS missense variant

Variant Summary

Nucleotide change: c.1001C>A
Protein / Detail: p.Thr334Asn
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Inconclusive
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	28.38
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.832
AlphaMissense	0.847
CADD Phred	26.1
SIFT	0
PolyPhen-2	0.949
Grantham distance	65
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Sahli, C. et al. Molecular characterization of cystinosis patients: predominance of the CTNS c.829dup mutation in Center Tunisia patients: predominance of the CTNS c.829dup mutation in Center of Tunisia. BMC Genom. Data 27, 25 (2026).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.329G>T

CTNS splice site variant

Variant Summary

Nucleotide change: c.329G>T
Protein / Detail: Splicing variant
Exon / Intron: Exon 6
Variant Type: Splice site
Clinical Manifestation: Inconclusive
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	31.58
SpliceAI max gain	0.01
SpliceAI max loss	0.89
REVEL	0.407
AlphaMissense	0.111
CADD Phred	26.1
SIFT	0.09
PolyPhen-2	0.023
Grantham distance	109
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).

c.901-1G>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.901-1G>C
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).

>4194bp incl ex. 1-3

CTNS deletion variant

Variant Summary

Nucleotide change: >4194bp incl ex. 1-3
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 1-3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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CTNS Variant Map

References

Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).
Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).
Aradhya, S. et al. Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders. Genet. Med. 14, 594-603 (2012).

10217 bp, c.62-1083_551

CTNS deletion variant

Variant Summary

Nucleotide change: 10217 bp, c.62-1083_551
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 4-8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.1025_1048del24

CTNS deletion variant

Variant Summary

Nucleotide change: c.1025_1048del24
Protein / Detail: p.Ser342_Phe349del
Exon / Intron: Exon 12
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Aldahmesh, M.A. et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet. 30, 185-189 (2009).

c.492_515del24

CTNS deletion variant

Variant Summary

Nucleotide change: c.492_515del24
Protein / Detail: p.Leu165_Ala172del
Exon / Intron: Exon 8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Sadeghipour, F. et al. Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. Hum. Genome Var. 4, 17038 (2017).

ex. 5

CTNS deletion variant

Variant Summary

Nucleotide change: ex. 5
Protein / Detail: Large genomic deletion
Exon / Intron: Exon 5
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep. 6, 35395 (2016).
Besouw, M.T.P. et al. Non-invasive measurements of atherosclerosis in adult cystinosis patients. J. Inherit. Metab. Dis. 34, 811-818 (2011).
Ivanova, E.A. et al. Cystinosin deficiency causes podocyte damage and loss associated with increased cell motility. Kidney Int. 89, 1037-1048 (2016).

c.60_61delTG

CTNS deletion variant

Variant Summary

Nucleotide change: c.60_61delTG
Protein / Detail: p.Cys20*
Exon / Intron: Exon 3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Bertholet-Thomas, A. et al. Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment. Pediatr. Nephrol. 33, 1165-1172 (2018).

c.120delC

CTNS deletion variant

Variant Summary

Nucleotide change: c.120delC
Protein / Detail: p.Asn41Thrfs*10
Exon / Intron: Exon 4
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.291_294delTACT

CTNS deletion variant

Variant Summary

Nucleotide change: c.291_294delTACT
Protein / Detail: p.Thr98Phefs*19
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.561+1delG

CTNS splice site variant

Variant Summary

Nucleotide change: c.561+1delG
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.614_616delACG

CTNS deletion variant

Variant Summary

Nucleotide change: c.614_616delACG
Protein / Detail: p.Asp205del
Exon / Intron: Exon 9
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Capalbo, A. et al. Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet. 15, e1008409 (2019).

c.956_956delA

CTNS deletion variant

Variant Summary

Nucleotide change: c.956_956delA
Protein / Detail: p.Q319RfsX10
Exon / Intron: Exon 11
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).

c.1027_1038del12

CTNS deletion variant

Variant Summary

Nucleotide change: c.1027_1038del12
Protein / Detail: p.Ile343_Asp346del
Exon / Intron: Exon 12
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.92_93insG

CTNS insertion variant

Variant Summary

Nucleotide change: c.92_93insG
Protein / Detail: p.Val32Argfs*28
Exon / Intron: Exon 4
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.516dupC

CTNS insertion variant

Variant Summary

Nucleotide change: c.516dupC
Protein / Detail: p.Tyr173Leufs*55
Exon / Intron: Exon 8
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Capalbo, A. et al. Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet. 15, e1008409 (2019).

c.124G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.124G>A
Protein / Detail: p.Val42Ile
Exon / Intron: Exon 4
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Benign/Likely Benign
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	6.20
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.175
AlphaMissense	0.068
CADD Phred	4.514
SIFT	0.71
PolyPhen-2	0.001
Grantham distance	29
BLOSUM62	3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
1000 Genomes Project Consortium A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010).
Rodriguez-Flores, J.L. et al. Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar. Hum. Mutat. 35, 105-116 (2014).

c.250A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.250A>G
Protein / Detail: p.Asn84Asp
Exon / Intron: Exon 5
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	0.32
SpliceAI max gain	0.02
SpliceAI max loss	0
REVEL	0.17
AlphaMissense	0.064
CADD Phred	0.363
SIFT	0.22
PolyPhen-2	0
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.470G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.470G>A
Protein / Detail: p.Gly157Asp
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	30.21
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.973
AlphaMissense	0.986
CADD Phred	26.2
SIFT	0
PolyPhen-2	1
Grantham distance	94
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.517T>C

CTNS missense variant

Variant Summary

Nucleotide change: c.517T>C
Protein / Detail: p.Tyr173His
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	27.24
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.943
AlphaMissense	0.961
CADD Phred	29.6
SIFT	0
PolyPhen-2	1
Grantham distance	83
BLOSUM62	2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Sadeghipour, F. et al. Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. Hum. Genome Var. 4, 17038 (2017).
Monies, D. et al. Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population. Am. J. Hum. Genet. 104, 1182-1201 (2019).

c.599C>T

CTNS missense variant

Variant Summary

Nucleotide change: c.599C>T
Protein / Detail: p.Pro200Leu
Exon / Intron: Exon 9
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	25.31
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.92
AlphaMissense	0.547
CADD Phred	27.2
SIFT	0
PolyPhen-2	0.646
Grantham distance	98
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).

c.664C>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.664C>T
Protein / Detail: p.Gln222*
Exon / Intron: Exon 10
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	39.46
SpliceAI max gain	0
SpliceAI max loss	0
CADD Phred	41

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.853-3C>G

CTNS splice site variant

Variant Summary

Nucleotide change: c.853-3C>G
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Ocular
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	23.08
SpliceAI max gain	0.4
SpliceAI max loss	0.6
CADD Phred	21

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

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CTNS Variant Map

References

Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Bryzgalov, L.O. et al. Detection of regulatory SNPs in human genome using ChIP-seq ENCODE data. PLoS ONE 8, e78833 (2013).
Anikster, Y. et al. Ocular Nonnephropathic Cystinosis: Clinical, Biochemical, and Molecular Correlations. Pediatr. Res. 47, 17-23 (2000).

c.61_61+2delGGT

CTNS splice site variant

Variant Summary

Nucleotide change: c.61_61+2delGGT
Protein / Detail: Splicing variant
Exon / Intron: Exon 3
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

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CTNS Variant Map

References

Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Rohayem, J. et al. Testicular function in males with infantile nephropathic cystinosis. Hum. Reprod. 36, 1191-1204 (2021).

c.325_329delACCGG

CTNS deletion variant

Variant Summary

Nucleotide change: c.325_329delACCGG
Protein / Detail: p.Thr109Profs*14
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Doneray, H. et al. Infantile Nephropathic Cystinosis: A Novel CTNS Mutation. Eurasian J. Med. 49(2), (2017).
Kars, M.E. et al. The genetic structure of the Turkish population reveals high levels of variation and admixture. Proc. Natl. Acad. Sci. U.S.A. 118, e2026076118 (2021).

c.15G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.15G>A
Protein / Detail: p.Trp5*
Exon / Intron: Exon 3
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	43.85
SpliceAI max gain	0.07
SpliceAI max loss	0.14
CADD Phred	39

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).
Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.73A>T

CTNS missense variant

Variant Summary

Nucleotide change: c.73A>T
Protein / Detail: p.Ser25Cys
Exon / Intron: Exon 4
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	8.14
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.354
AlphaMissense	0.096
CADD Phred	9.246
SIFT	0.23
PolyPhen-2	0.229
Grantham distance	112
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.839A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.839A>G
Protein / Detail: p.Lys280Arg
Exon / Intron: Exon 10
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	36.92
SpliceAI max gain	0.94
SpliceAI max loss	0.41
REVEL	0.912
AlphaMissense	0.66
CADD Phred	35
SIFT	0
PolyPhen-2	0.997
BLOSUM62	2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Thoene, J. et al. Mutations of CTNS causing intermediate cystinosis. Mol. Genet. Metab. 67, 283-293 (1999).
Servais, A. et al. Late-Onset Nephropathic Cystinosis Clinical Presentation, Outcome, and Genotyping Clinical Presentation, Outcome, and Genotyping. Clin. J. Am. Soc. Nephrol. 3, 27-35 (2008).

c.870C>G

CTNS nonsense variant

Variant Summary

Nucleotide change: c.870C>G
Protein / Detail: p.Tyr290*
Exon / Intron: Exon 11
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	35.26
SpliceAI max gain	0.06
SpliceAI max loss	0.07
CADD Phred	39

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Ceyhan-Birsoy, O. et al. Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. Am. J. Hum. Genet. 104, 76-93 (2019).

c.923G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.923G>A
Protein / Detail: p.Gly308Glu
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	31.15
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.991
AlphaMissense	0.987
CADD Phred	32
SIFT	0
PolyPhen-2	1
Grantham distance	98
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Shahkarami, S. et al. The first molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran. Nefrologia 33, 308-315 (2013).

c.61+5G>T

CTNS splice site variant

Variant Summary

Nucleotide change: c.61+5G>T
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	37.18
SpliceAI max gain	0
SpliceAI max loss	0.93
CADD Phred	22

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).

c.140+5G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.140+5G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	29.16
SpliceAI max gain	0
SpliceAI max loss	0.33
CADD Phred	19.98

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Guan, Y.-J. et al. Case Report: Cystinosis in a Chinese Child With a Novel CTNS Pathogenic Variant. Front. Pediatr. 10, 860990 (2022).

c.225+5GT>CC

CTNS splice site variant

Variant Summary

Nucleotide change: c.225+5GT>CC
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Kleta, R. et al. CTNS mutations in African American patients with cystinosis. Mol. Genet. Metab. 74, 332-337 (2001).

c.462-10C>G

CTNS splice site variant

Variant Summary

Nucleotide change: c.462-10C>G
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	24.84
SpliceAI max gain	1
SpliceAI max loss	0.99
CADD Phred	17.59

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.561+1G>T

CTNS splice site variant

Variant Summary

Nucleotide change: c.561+1G>T
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	30.42
SpliceAI max gain	0.03
SpliceAI max loss	1
CADD Phred	33

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.853-1G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.853-1G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	28.89
SpliceAI max gain	0.9
SpliceAI max loss	0.99
CADD Phred	35

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.971-1G>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.971-1G>C
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	30.43
SpliceAI max gain	0.74
SpliceAI max loss	0.97
CADD Phred	34

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Sahli, C. et al. Molecular characterization of cystinosis patients: predominance of the CTNS c.829dup mutation in Center Tunisia patients: predominance of the CTNS c.829dup mutation in Center of Tunisia. BMC Genom. Data 27, 25 (2026).

15kb

CTNS deletion variant

Variant Summary

Nucleotide change: 15kb
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 1-3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Hollenbeck, D. et al. Clinical relevance of small copy-number variants in chromosomal microarray clinical testing. Genet. Med. 19, 377-385 (2017).

20,327bp incl ex. 1-5 & part of intron 1 of CARKL

CTNS deletion variant

Variant Summary

Nucleotide change: 20,327bp incl ex. 1-5 & part of intron 1 of CARKL
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 1-5
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Chkioua, L. et al. Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene. Meta Gene 5, 144-149 (2015).

c.61+2406_225+3028del9287

CTNS deletion variant

Variant Summary

Nucleotide change: c.61+2406_225+3028del9287
Protein / Detail: p.Glu21Glyfs*49
Exon / Intron: Exons 4-5
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Geographic distribution data for this variant is not yet available in this database.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Papizh, S. et al. CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report. BMC Nephrol. 20, 400 (2019).

c.62-1083_551del10216

CTNS deletion variant

Variant Summary

Nucleotide change: c.62-1083_551del10216
Protein / Detail: p.Glu21Alafs*15
Exon / Intron: Exons 4-8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).

ex. 6-13 g.3558266-3565849)

CTNS deletion variant

Variant Summary

Nucleotide change: ex. 6-13 g.3558266-3565849)
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 6-13
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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Explore CTNS Gene

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CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

ex. 6-7 g.(3558266-3558736)

CTNS deletion variant

Variant Summary

Nucleotide change: ex. 6-7 g.(3558266-3558736)
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 6-7
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

incl. ex. 4-5 g(3550706-3552123)

CTNS deletion variant

Variant Summary

Nucleotide change: incl. ex. 4-5 g(3550706-3552123)
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 4-5
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

ex. 3 c.(-20+1_19-1)_(61+1_62-1)

CTNS deletion variant

Variant Summary

Nucleotide change: ex. 3 c.(-20+1_19-1)_(61+1_62-1)
Protein / Detail: Large genomic deletion
Exon / Intron: Exon 3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.40delC

CTNS deletion variant

Variant Summary

Nucleotide change: c.40delC
Protein / Detail: p.Leu14*
Exon / Intron: Exon 3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).
Alcántara-Ortigoza, M.A. et al. CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis. J. Pediatr. Genet. 2, 129-132 (2013).

c.61_61+1delinsCT

CTNS splice site variant

Variant Summary

Nucleotide change: c.61_61+1delinsCT
Protein / Detail: p.Glu21LeufsTer39
Exon / Intron: Exon 3
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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References

Sinha, R. et al. Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study. Pediatr. Nephrol. 37, 1811-1836 (2022).

c.225+5_225+6delCT/insCC

CTNS splice site variant

Variant Summary

Nucleotide change: c.225+5_225+6delCT/insCC
Protein / Detail: Splicing variant
Exon / Intron: Exon 5
Variant Type: Splice site
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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References

Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).
Cabrera-Serrano, M. et al. Cystinosis distal myopathy, novel clinical, pathological and genetic features. Neuromuscul. Disord. 27, 873-878 (2017).

c.280delG

CTNS deletion variant

Variant Summary

Nucleotide change: c.280delG
Protein / Detail: p.Val94Leufs*24
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).

c.297_312del

CTNS deletion variant

Variant Summary

Nucleotide change: c.297_312del
Protein / Detail: p.Tyr100ThrfsX13
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Martín-Begué, N. et al. Intracranial Hypertension in Cystinosis Is a Challenge: Experience in a Children's Hospital. JIMD Rep. 35, 17-22 (2017).

c.320_323delATCA

CTNS deletion variant

Variant Summary

Nucleotide change: c.320_323delATCA
Protein / Detail: p.Asn107Argfs*10
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.329+1delG

CTNS splice site variant

Variant Summary

Nucleotide change: c.329+1delG
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Yang, Y. et al. First Report of CTNS Mutations in a Chinese Family with Infantile Cystinosis. Sci. World J. 2015, 309410 (2015).

c.423delC

CTNS deletion variant

Variant Summary

Nucleotide change: c.423delC
Protein / Detail: p.Phe142Serfs*5
Exon / Intron: Exon 7
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.463_464delGT

CTNS deletion variant

Variant Summary

Nucleotide change: c.463_464delGT
Protein / Detail: p.Val155Hisfs*72
Exon / Intron: Exon 8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Yang, Y. et al. First Report of CTNS Mutations in a Chinese Family with Infantile Cystinosis. Sci. World J. 2015, 309410 (2015).

c.529delA

CTNS deletion variant

Variant Summary

Nucleotide change: c.529delA
Protein / Detail: p.N177Tfs*
Exon / Intron: Exon 8
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Sahli, C. et al. Molecular characterization of cystinosis patients: predominance of the CTNS c.829dup mutation in Center Tunisia patients: predominance of the CTNS c.829dup mutation in Center of Tunisia. BMC Genom. Data 27, 25 (2026).

c.558_585del

CTNS deletion variant

Variant Summary

Nucleotide change: c.558_585del
Protein / Detail: p.Lys187ThrfsX3
Exon / Intron: Exon 9
Variant Type: Deletion
Clinical Manifestation: Unclassified
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.619del

CTNS deletion variant

Variant Summary

Nucleotide change: c.619del
Protein / Detail: p.Phe207SerfsX11
Exon / Intron: Exon 9
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.681+7delC

CTNS splice site variant

Variant Summary

Nucleotide change: c.681+7delC
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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References

Chkioua, L. et al. Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis. Diagn. Pathol. 17, 44 (2022).

c.751_754delACCAinsCG

CTNS deletion variant

Variant Summary

Nucleotide change: c.751_754delACCAinsCG
Protein / Detail: Large genomic deletion
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).

c.751_752del

CTNS deletion variant

Variant Summary

Nucleotide change: c.751_752del
Protein / Detail: p.Thr251Hisfs*44
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).

c.770_792del23

CTNS deletion variant

Variant Summary

Nucleotide change: c.770_792del23
Protein / Detail: fsN288X
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.807_809delCTC

CTNS deletion variant

Variant Summary

Nucleotide change: c.807_809delCTC
Protein / Detail: p.Ser270del
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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References

Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.-303 TG Ins

CTNS promoter variant

Variant Summary

Nucleotide change: c.-303 TG Ins
Protein / Detail: Promoter region variant
Exon / Intron: Promoter
Variant Type: Promoter
Clinical Manifestation: Ocular
ClinVar Pathogenicity: Undefined

Geographic Distribution

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.140+2dupT

CTNS splice site variant

Variant Summary

Nucleotide change: c.140+2dupT
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Conflicting

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.152_153insCT

CTNS insertion variant

Variant Summary

Nucleotide change: c.152_153insCT
Protein / Detail: p.Ala52Leufs*5
Exon / Intron: Exon 5
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Shahkarami, S. et al. The first molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran. Nefrologia 33, 308-315 (2013).

c.292dupA

CTNS insertion variant

Variant Summary

Nucleotide change: c.292dupA
Protein / Detail: p.Thr98Asnfs*27
Exon / Intron: Exon 6
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).

c.330-14_441dup

CTNS splice site variant

Variant Summary

Nucleotide change: c.330-14_441dup
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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References

Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.660_661insT

CTNS insertion variant

Variant Summary

Nucleotide change: c.660_661insT
Protein / Detail: p.Val221Cysfs*7
Exon / Intron: Exon 9
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.969dupC

CTNS insertion variant

Variant Summary

Nucleotide change: c.969dupC
Protein / Detail: p.Asp324ArgfsX41
Exon / Intron: Exon 11
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.971_972insC

CTNS insertion variant

Variant Summary

Nucleotide change: c.971_972insC
Protein / Detail: p.Q325PfsX40
Exon / Intron: Exon 12
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).

-303G>T

CTNS promoter variant

Variant Summary

Nucleotide change: -303G>T
Protein / Detail: Promoter region variant
Exon / Intron: Promoter
Variant Type: Promoter
Clinical Manifestation: Ocular
ClinVar Pathogenicity: Undefined

Geographic Distribution

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).
Phornphutkul, C. et al. The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region. Am. J. Hum. Genet. 69, 712-721 (2001).

c.1A>C

CTNS missense variant

Variant Summary

Nucleotide change: c.1A>C
Protein / Detail: p.Met1Leu
Exon / Intron: Exon 3
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	30.13
SpliceAI max gain	0.07
SpliceAI max loss	0
CADD Phred	19.06
SIFT	0.25
PolyPhen-2	0.091
Grantham distance	15
BLOSUM62	2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This variant affects the initiator start codon (Met1) of the CTNS coding sequence. Since translation of the CTNS open reading frame normally begins at this codon, the predicted outcome is that no CTNS amino acid sequence is translated from this transcript at all (barring the use of an alternative, non-canonical downstream start codon, which is not modeled here). Because there is no resulting CTNS protein product to depict, no 3D structure prediction is shown for this variant.

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References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.14G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.14G>A
Protein / Detail: p.Trp5*
Exon / Intron: Exon 3
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	43.82
SpliceAI max gain	0
SpliceAI max loss	0.35
CADD Phred	40

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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References

Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.262C>A

CTNS missense variant

Variant Summary

Nucleotide change: c.262C>A
Protein / Detail: p.Gln88Lys
Exon / Intron: Exon 6
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	23.57
SpliceAI max gain	0
SpliceAI max loss	0.06
REVEL	0.244
AlphaMissense	0.077
CADD Phred	20.3
SIFT	0.4
PolyPhen-2	0.003
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Chkioua, L. et al. Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis. Diagn. Pathol. 17, 44 (2022).

c.397A>T

CTNS missense variant

Variant Summary

Nucleotide change: c.397A>T
Protein / Detail: p.Ile133Phe
Exon / Intron: Exon 7
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	21.20
SpliceAI max gain	0.1
SpliceAI max loss	0.31
REVEL	0.933
AlphaMissense	0.16
CADD Phred	27.8
SIFT	0.02
PolyPhen-2	0.973
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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References

McGowan-Jordan, J. et al. Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation. Eur. J. Hum. Genet. 7, 671-678 (1999).

c.416C>A

CTNS missense variant

Variant Summary

Nucleotide change: c.416C>A
Protein / Detail: p.Ser139Tyr
Exon / Intron: Exon 7
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	31.95
SpliceAI max gain	0.01
SpliceAI max loss	0.08
REVEL	0.951
AlphaMissense	0.972
CADD Phred	29.9
SIFT	0
PolyPhen-2	0.992
Grantham distance	144
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Chkioua, L. et al. Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis. Diagn. Pathol. 17, 44 (2022).

c.506G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.506G>A
Protein / Detail: p.Gly169Asp
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	30.39
SpliceAI max gain	0.01
SpliceAI max loss	0
REVEL	0.994
AlphaMissense	0.985
CADD Phred	29.3
SIFT	0
PolyPhen-2	1
Grantham distance	94
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).

c.627C>A

CTNS missense variant

Variant Summary

Nucleotide change: c.627C>A
Protein / Detail: p.Ser209Arg
Exon / Intron: Exon 9
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	26.05
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.865
AlphaMissense	0.997
CADD Phred	23.5
SIFT	0
PolyPhen-2	0.945
Grantham distance	110
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.705G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.705G>A
Protein / Detail: p.Trp235*
Exon / Intron: Exon 10
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	36.91
SpliceAI max gain	0
SpliceAI max loss	0.02
CADD Phred	41

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Pennesi, M. et al. A new mutation in two siblings with cystinosis presenting with Bartter syndrome. Pediatr. Nephrol. 20, 217-219 (2005).

c.809C>T

CTNS missense variant

Variant Summary

Nucleotide change: c.809C>T
Protein / Detail: p.Ser270Phe
Exon / Intron: Exon 10
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	30.26
SpliceAI max gain	0.01
SpliceAI max loss	0.02
REVEL	0.951
AlphaMissense	0.952
CADD Phred	32
SIFT	0
PolyPhen-2	0.998
Grantham distance	155
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Owen, E.P. et al. Common mutation causes cystinosis in the majority of black South African patients. Pediatr. Nephrol. 30, 595-601 (2015).

c.852G>T

CTNS missense variant

Variant Summary

Nucleotide change: c.852G>T
Protein / Detail: p.Gln284His
Exon / Intron: Exon 10
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	50.79
SpliceAI max gain	0.38
SpliceAI max loss	0.92
REVEL	0.95
AlphaMissense	0.992
CADD Phred	36
SIFT	0
PolyPhen-2	0.999
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).

c.850C>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.850C>T
Protein / Detail: p.Gln284*
Exon / Intron: Exon 10
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	46.20
SpliceAI max gain	0.17
SpliceAI max loss	0.48
CADD Phred	57

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Yeetong, P. et al. Two novel CTNS mutations in cystinosis patients in Thailand.. Gene 499, 323-325 (2012).

c.864C>A

CTNS missense variant

Variant Summary

Nucleotide change: c.864C>A
Protein / Detail: p.Asn288Lys
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	26.77
SpliceAI max gain	0
SpliceAI max loss	0.03
REVEL	0.858
AlphaMissense	0.994
CADD Phred	25
SIFT	0
PolyPhen-2	1
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.873C>G

CTNS nonsense variant

Variant Summary

Nucleotide change: c.873C>G
Protein / Detail: p.Tyr291*
Exon / Intron: Exon 11
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	40.26
SpliceAI max gain	0.18
SpliceAI max loss	0.06
CADD Phred	43

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Quinaux, T. et al. Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation. Cells 10, 2498 (2021).

c.890G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.890G>A
Protein / Detail: p.Trp297*
Exon / Intron: Exon 11
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	39.61
SpliceAI max gain	0
SpliceAI max loss	0.02
CADD Phred	48

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Jaradat, S. et al. Molecular analysis of the CTNS gene in Jordanian families with nephropathic cystinosis. Nefrologia 35, 547-553 (2015).

c.914A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.914A>G
Protein / Detail: p.Asp305Gly
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	28.82
SpliceAI max gain	0
SpliceAI max loss	0.02
REVEL	0.988
AlphaMissense	0.994
CADD Phred	32
SIFT	0
PolyPhen-2	1
Grantham distance	94
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.913G>T

CTNS missense variant

Variant Summary

Nucleotide change: c.913G>T
Protein / Detail: p.Asp305Tyr
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	31.49
SpliceAI max gain	0.01
SpliceAI max loss	0.01
REVEL	0.987
AlphaMissense	0.98
CADD Phred	33
SIFT	0.01
PolyPhen-2	1
Grantham distance	160
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).
Chiavérini, C. et al. In vivo reflectance confocal microscopy of the skin: A noninvasive means of assessing body cystine accumulation in infantile cystinosis. J. Am. Acad. Dermatol. 68, e111-e116 (2013).

c.922G>C

CTNS missense variant

Variant Summary

Nucleotide change: c.922G>C
Protein / Detail: p.Gly308Arg
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	34.03
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.991
AlphaMissense	0.978
CADD Phred	32
SIFT	0
PolyPhen-2	1
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.1009G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.1009G>A
Protein / Detail: p.Gly337Arg
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	30.93
SpliceAI max gain	0.01
SpliceAI max loss	0.05
REVEL	0.918
AlphaMissense	0.954
CADD Phred	29.8
SIFT	0
PolyPhen-2	0.994
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).

c.1013T>C

CTNS missense variant

Variant Summary

Nucleotide change: c.1013T>C
Protein / Detail: p.Leu338Pro
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	27.66
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.981
AlphaMissense	0.988
CADD Phred	27.2
SIFT	0
PolyPhen-2	0.999
Grantham distance	98
BLOSUM62	-3

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.1062C>A

CTNS missense variant

Variant Summary

Nucleotide change: c.1062C>A
Protein / Detail: p.Phe354Leu
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	28.01
SpliceAI max gain	0
SpliceAI max loss	0.08
REVEL	0.637
AlphaMissense	0.917
CADD Phred	23.1
SIFT	0
PolyPhen-2	0.105
BLOSUM62	0

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

El Naofal, M. et al. The genomic landscape of rare disorders in the Middle East. Genome Med. 15, 5 (2023).

c.61-61+2delGGT

CTNS splice site variant

Variant Summary

Nucleotide change: c.61-61+2delGGT
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).

c.141-1G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.141-1G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	33.30
SpliceAI max gain	0.01
SpliceAI max loss	0.98
CADD Phred	31

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).

c.225+1G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.225+1G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	34.02
SpliceAI max gain	0
SpliceAI max loss	0.96
CADD Phred	32

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.225+5G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.225+5G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	34.04
SpliceAI max gain	0
SpliceAI max loss	0.96
CADD Phred	17.25

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).

c.226-3C>G

CTNS splice site variant

Variant Summary

Nucleotide change: c.226-3C>G
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	27.87
SpliceAI max gain	0.01
SpliceAI max loss	0.96
CADD Phred	15.95

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Cabrera-Serrano, M. et al. Cystinosis distal myopathy, novel clinical, pathological and genetic features. Neuromuscul. Disord. 27, 873-878 (2017).

c.329G>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.329G>C
Protein / Detail: Splicing variant
Exon / Intron: Exon 6
Variant Type: Splice site
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	30.36
SpliceAI max gain	0.02
SpliceAI max loss	0.9
REVEL	0.316
AlphaMissense	0.094
CADD Phred	25.4
SIFT	0.11
PolyPhen-2	0.023
Grantham distance	60
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Higashi, S. et al. Diagnostic challenge in a patient with nephropathic juvenile cystinosis: a case report. BMC Nephrol. 18, 300 (2017).

c.329+2T>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.329+2T>C
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	27.65
SpliceAI max gain	0.03
SpliceAI max loss	0.93
CADD Phred	26.5

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Higashi, S. et al. Diagnostic challenge in a patient with nephropathic juvenile cystinosis: a case report. BMC Nephrol. 18, 300 (2017).

c.562-1G>C

CTNS splice site variant

Variant Summary

Nucleotide change: c.562-1G>C
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	32.34
SpliceAI max gain	0.37
SpliceAI max loss	0.99
CADD Phred	34

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).

c.853-7G>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.853-7G>A
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Unclassified
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	25.00
SpliceAI max gain	1
SpliceAI max loss	0.4
CADD Phred	23.2

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Veys, K. et al. Urine-Derived Kidney Progenitor Cells in Cystinosis. Cells 11, 1245 (2022).

c.853-2A>G

CTNS splice site variant

Variant Summary

Nucleotide change: c.853-2A>G
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	26.66
SpliceAI max gain	0.61
SpliceAI max loss	0.99
CADD Phred	34

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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References

Bertholet-Thomas, A. et al. Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment. Pediatr. Nephrol. 33, 1165-1172 (2018).

c.854C>A

CTNS splice site variant

Variant Summary

Nucleotide change: c.854C>A
Protein / Detail: Splicing variant
Exon / Intron: Exon 11
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	27.49
SpliceAI max gain	0
SpliceAI max loss	0.03
REVEL	0.957
AlphaMissense	0.972
CADD Phred	28.6
SIFT	0
PolyPhen-2	0.995
Grantham distance	126
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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References

Won, J.Y. et al. A case of corneal cystinosis in a patient with rickets and chronic renal failure. Indian J. Ophthalmol. 63, 785-787 (2015).

40 kb incl. entire gene + SHPK

CTNS deletion variant

Variant Summary

Nucleotide change: 40 kb incl. entire gene + SHPK
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 3-12
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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References

Villela, D. et al. Germline DNA copy number variation in individuals with Argyrophilic grain disease reveals CTNS as a plausible candidate gene. Genet. Mol. Biol. 36, 498-501 (2013).

651delTCAC

CTNS deletion variant

Variant Summary

Nucleotide change: 651delTCAC
Protein / Detail: Large genomic deletion
Exon / Intron: Exon 9
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).

ex 4 c.(61+1_62-1)_(140+1_140-1)

CTNS deletion variant

Variant Summary

Nucleotide change: ex 4 c.(61+1_62-1)_(140+1_140-1)
Protein / Detail: Large genomic deletion
Exon / Intron: Exon 4
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

incl ex. 6-10 (c.(225+1_226-1)_(852+1_853-1)del)

CTNS deletion variant

Variant Summary

Nucleotide change: incl ex. 6-10 (c.(225+1_226-1)_(852+1_853-1)del)
Protein / Detail: Large genomic deletion
Exon / Intron: Exons 6-10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this large deletion (highlighted bar) relative to the CTNS gene structure.

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References

Mallett, A.J. et al. Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders. Kidney Int. 92, 1493-1506 (2017).

c.27del

CTNS deletion variant

Variant Summary

Nucleotide change: c.27del
Protein / Detail: p.Phe9LeufsX6
Exon / Intron: Exon 3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.36delT

CTNS deletion variant

Variant Summary

Nucleotide change: c.36delT
Protein / Detail: p.Leu14*
Exon / Intron: Exon 3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).

c.225+1del4

CTNS splice site variant

Variant Summary

Nucleotide change: c.225+1del4
Protein / Detail: Splicing variant
Exon / Intron: Exon 5
Variant Type: Splice site
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.260_261delTT

CTNS deletion variant

Variant Summary

Nucleotide change: c.260_261delTT
Protein / Detail: p.Phe87Serfs*37
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).

c.295_310del16

CTNS deletion variant

Variant Summary

Nucleotide change: c.295_310del16
Protein / Detail: p.Val99Ilefs*14
Exon / Intron: Exon 6
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).

c.400_402del

CTNS deletion variant

Variant Summary

Nucleotide change: c.400_402del
Protein / Detail: p.Tyr134del
Exon / Intron: Exon 7
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.462-27_426-3del

CTNS splice site variant

Variant Summary

Nucleotide change: c.462-27_426-3del
Protein / Detail: Splicing variant
Exon / Intron: Intron
Variant Type: Splice site
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this splice-site variant relative to the CTNS gene structure.

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References

Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).

c.659_665delTCGTGCCA

CTNS deletion variant

Variant Summary

Nucleotide change: c.659_665delTCGTGCCA
Protein / Detail: p.Ile220Serfs*31
Exon / Intron: Exon 9
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).

c.696_697del

CTNS deletion variant

Variant Summary

Nucleotide change: c.696_697del
Protein / Detail: p.Ser234Leufs*61
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Unclassified
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.790_791delCA

CTNS deletion variant

Variant Summary

Nucleotide change: c.790_791delCA
Protein / Detail: p.Gln264Valfs*31
Exon / Intron: Exon 10
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).

c.1000delA

CTNS deletion variant

Variant Summary

Nucleotide change: c.1000delA
Protein / Detail: p.Thr334Profs*33
Exon / Intron: Exon 12
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.1036_1047del12

CTNS deletion variant

Variant Summary

Nucleotide change: c.1036_1047del12
Protein / Detail: p.Asp346_Phe349del
Exon / Intron: Exon 12
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Conflicting

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.266dup

CTNS insertion variant

Variant Summary

Nucleotide change: c.266dup
Protein / Detail: p.Thr90AspfsX35
Exon / Intron: Exon 6
Variant Type: Insertion
Clinical Manifestation: Unclassified
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).

c.354_346insCACTT

CTNS insertion variant

Variant Summary

Nucleotide change: c.354_346insCACTT
Protein / Detail: p.Leu116Hisfs*2
Exon / Intron: Exon 7
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).

c.587dupA

CTNS insertion variant

Variant Summary

Nucleotide change: c.587dupA
Protein / Detail: p.Asn196fs
Exon / Intron: Exon 9
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Bitsori, M. et al. Slow progression of renal failure in a child with infantile cystinosis. CEN Case Rep. 7, 153-157 (2018).

c.841dup

CTNS insertion variant

Variant Summary

Nucleotide change: c.841dup
Protein / Detail: p.Ser310Alafs*55
Exon / Intron: Exon 10
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.927_928insG

CTNS insertion variant

Variant Summary

Nucleotide change: c.927_928insG
Protein / Detail: p.Ser310Glnfs*55
Exon / Intron: Exon 11
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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References

Wilmer, M.J. et al. Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim. Biophys. Acta 1812, 643-651 (2011).

c.1032delCinsTG

CTNS deletion variant

Variant Summary

Nucleotide change: c.1032delCinsTG
Protein / Detail: F345Cfs*19
Exon / Intron: Exon 12
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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CTNS Variant Map

References

Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).

c.1047_1048ins12

CTNS insertion variant

Variant Summary

Nucleotide change: c.1047_1048ins12
Protein / Detail: p.Phe349_Phe350insAspValGluPhe
Exon / Intron: Exon 12
Variant Type: Insertion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.-520T>C

CTNS promoter variant

Variant Summary

Nucleotide change: c.-520T>C
Protein / Detail: Promoter region variant
Exon / Intron: Promoter
Variant Type: Promoter
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Benign
gnomAD: View in gnomAD →

Geographic Distribution

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CTNS Variant Map

References

Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).

c.-512 G>C

CTNS promoter variant

Variant Summary

Nucleotide change: c.-512 G>C
Protein / Detail: Promoter region variant
Exon / Intron: Promoter
Variant Type: Promoter
Clinical Manifestation: Unclassified
ClinVar Pathogenicity: Undefined

Geographic Distribution

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References

Fleige, T. et al. Next generation sequencing as second-tier test in high-throughput newborn screening for nephropathic cystinosis. Eur. J. Hum. Genet. 28, 193-201 (2020).

-303 insT

CTNS promoter variant

Variant Summary

Nucleotide change: -303 insT
Protein / Detail: Promoter region variant
Exon / Intron: Promoter
Variant Type: Promoter
Clinical Manifestation: Ocular
ClinVar Pathogenicity: Undefined

Geographic Distribution

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CTNS Variant Map

References

Phornphutkul, C. et al. The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if mutated in a critical region. Am. J. Hum. Genet. 69, 712-721 (2001).

c.3G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.3G>A
Protein / Detail: p.Met1Ile
Exon / Intron: Exon 3
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	34.00
SpliceAI max gain	0
SpliceAI max loss	0.12
CADD Phred	21.8
SIFT	0.01
PolyPhen-2	0.266
Grantham distance	10
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This variant affects the initiator start codon (Met1) of the CTNS coding sequence. Since translation of the CTNS open reading frame normally begins at this codon, the predicted outcome is that no CTNS amino acid sequence is translated from this transcript at all (barring the use of an alternative, non-canonical downstream start codon, which is not modeled here). Because there is no resulting CTNS protein product to depict, no 3D structure prediction is shown for this variant.

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CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.3G>C

CTNS missense variant

Variant Summary

Nucleotide change: c.3G>C
Protein / Detail: p.Met1Ile
Exon / Intron: Exon 3
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	34.13
SpliceAI max gain	0.03
SpliceAI max loss	0
CADD Phred	21.8
SIFT	0.01
PolyPhen-2	0.266
Grantham distance	10
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This variant affects the initiator start codon (Met1) of the CTNS coding sequence. Since translation of the CTNS open reading frame normally begins at this codon, the predicted outcome is that no CTNS amino acid sequence is translated from this transcript at all (barring the use of an alternative, non-canonical downstream start codon, which is not modeled here). Because there is no resulting CTNS protein product to depict, no 3D structure prediction is shown for this variant.

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CTNS Variant Map

References

Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.116C>T

CTNS missense variant

Variant Summary

Nucleotide change: c.116C>T
Protein / Detail: p.Ser39Leu
Exon / Intron: Exon 4
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Conflicting
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	21.30
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.302
AlphaMissense	0.095
CADD Phred	19.54
SIFT	0.12
PolyPhen-2	0.04
Grantham distance	145
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Guey, S. et al. Biallelic variants in NOS3 and GUCY1A3, the two major genes of the nitric oxide pathway, cause moyamoya cerebral angiopathy. Hum. Genomics 17, 24 (2023).

c.119C>G

CTNS missense variant

Variant Summary

Nucleotide change: c.119C>G
Protein / Detail: p.Thr40Ser
Exon / Intron: Exon 4
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	18.06
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.203
AlphaMissense	0.089
CADD Phred	11.01
SIFT	0.34
PolyPhen-2	0.017
Grantham distance	58
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).

c.274C>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.274C>T
Protein / Detail: p.Gln92*
Exon / Intron: Exon 6
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	37.02
SpliceAI max gain	0
SpliceAI max loss	0.15
CADD Phred	38

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Li, X.-Q. et al. The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population. J. Pediatr. Endocrinol. Metab. 32, 375-382 (2019).

c.319A>C

CTNS missense variant

Variant Summary

Nucleotide change: c.319A>C
Protein / Detail: p.Asn107His
Exon / Intron: Exon 6
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	20.24
SpliceAI max gain	0.01
SpliceAI max loss	0.02
REVEL	0.301
AlphaMissense	0.084
CADD Phred	20.4
SIFT	0.07
PolyPhen-2	0.007
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Gheldof, A. et al. Clinical implementation of gene panel testing for lysosomal storage diseases storage diseases. Mol. Genet. Genomic Med. 7, e00527 (2019).

c.413G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.413G>A
Protein / Detail: p.Trp138*
Exon / Intron: Exon 7
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

In Silico Predictions

AlphaGenome AVI (Phred)	41.07
SpliceAI max gain	0.07
SpliceAI max loss	0.33
CADD Phred	48

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.450G>A

CTNS nonsense variant

Variant Summary

Nucleotide change: c.450G>A
Protein / Detail: p.Trp150*
Exon / Intron: Exon 7
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	38.93
SpliceAI max gain	0
SpliceAI max loss	0.02
CADD Phred	47

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.477C>G

CTNS missense variant

Variant Summary

Nucleotide change: c.477C>G
Protein / Detail: p.Ser159Arg
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	26.53
SpliceAI max gain	0.01
SpliceAI max loss	0
REVEL	0.859
AlphaMissense	0.986
CADD Phred	24.3
SIFT	0
PolyPhen-2	0.98
Grantham distance	110
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Li, X.-Q. et al. The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population. J. Pediatr. Endocrinol. Metab. 32, 375-382 (2019).

c.505G>T

CTNS missense variant

Variant Summary

Nucleotide change: c.505G>T
Protein / Detail: p.Gly169Cys
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	29.73
SpliceAI max gain	0.03
SpliceAI max loss	0
REVEL	0.967
AlphaMissense	0.941
CADD Phred	31
SIFT	0
PolyPhen-2	1
Grantham distance	159
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).

c.530A>C

CTNS missense variant

Variant Summary

Nucleotide change: c.530A>C
Protein / Detail: p.Asn177Thr
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	24.40
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.846
AlphaMissense	0.575
CADD Phred	26.3
SIFT	0
PolyPhen-2	0.842
Grantham distance	65
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Kalatzis, V. et al. Identification of 14 Novel CTNS Mutations and Characterization of Seven Splice Site Mutations Associated With Cystinosis. Hum. Mutat. 20, 439-446 (2002).

c.544T>C

CTNS missense variant

Variant Summary

Nucleotide change: c.544T>C
Protein / Detail: p.Trp182Arg
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	25.56
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.897
AlphaMissense	0.778
CADD Phred	26.7
SIFT	0
PolyPhen-2	0.842
Grantham distance	101
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).

c.560A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.560A>G
Protein / Detail: p.Lys187Arg
Exon / Intron: Exon 8
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	22.61
SpliceAI max gain	0.01
SpliceAI max loss	0.08
REVEL	0.793
AlphaMissense	0.087
CADD Phred	25.2
SIFT	0.05
PolyPhen-2	0.005
BLOSUM62	2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).

c.565C>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.565C>T
Protein / Detail: p.Q189*
Exon / Intron: Exon 9
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	35.50
SpliceAI max gain	0.06
SpliceAI max loss	0.02
CADD Phred	40

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).

c.629T>C

CTNS missense variant

Variant Summary

Nucleotide change: c.629T>C
Protein / Detail: p.Leu210Pro
Exon / Intron: Exon 9
Variant Type: Missense
Clinical Manifestation: Juvenile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	27.15
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.943
AlphaMissense	0.94
CADD Phred	27.7
SIFT	0
PolyPhen-2	0.799
Grantham distance	98
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).

c.635C>T

CTNS missense variant

Variant Summary

Nucleotide change: c.635C>T
Protein / Detail: p.Ala212Val
Exon / Intron: Exon 9
Variant Type: Missense
Clinical Manifestation: Ocular
ClinVar Pathogenicity: Pathogenic/Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	29.15
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.882
AlphaMissense	0.902
CADD Phred	26.2
SIFT	0
PolyPhen-2	0.992
Grantham distance	64
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Browning, A.C. et al. A case of ocular cystinosis associated with two potentially severe CTNS mutations. Ophthalmic Genet. 40, 157-160 (2019).

c.647C>G

CTNS missense variant

Variant Summary

Nucleotide change: c.647C>G
Protein / Detail: p.Thr216Arg
Exon / Intron: Exon 9
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	28.82
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.911
AlphaMissense	0.873
CADD Phred	24.7
SIFT	0
PolyPhen-2	0.802
Grantham distance	71
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).

c.680A>T

CTNS missense variant

Variant Summary

Nucleotide change: c.680A>T
Protein / Detail: p.Glu227Val
Exon / Intron: Exon 10
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	29.94
SpliceAI max gain	0.81
SpliceAI max loss	0.02
REVEL	0.912
AlphaMissense	0.323
CADD Phred	35
SIFT	0
PolyPhen-2	0.332
Grantham distance	121
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Li, X.-Q. et al. The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population. J. Pediatr. Endocrinol. Metab. 32, 375-382 (2019).

c.695G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.695G>A
Protein / Detail: p.Arg232His
Exon / Intron: Exon 10
Variant Type: Missense
Clinical Manifestation: Ocular
ClinVar Pathogenicity: Conflicting
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	6.84
SpliceAI max gain	0.01
SpliceAI max loss	0
REVEL	0.228
AlphaMissense	0.073
CADD Phred	11.89
SIFT	0.08
PolyPhen-2	0.022
BLOSUM62	0

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Rasouly, H.M. et al. The Burden of Candidate Pathogenic Variants for Kidney and Genitourinary Disorders Emerging From Exome Sequencing. Ann. Intern. Med. 170, 11-21 (2019).

c.861G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.861G>A
Protein / Detail: p.Met287Ile
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	27.51
SpliceAI max gain	0.07
SpliceAI max loss	0.01
REVEL	0.886
AlphaMissense	0.703
CADD Phred	26.3
SIFT	0
PolyPhen-2	0.151
Grantham distance	10
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).

c.878G>T

CTNS missense variant

Variant Summary

Nucleotide change: c.878G>T
Protein / Detail: p.Ser293Ile
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	29.94
SpliceAI max gain	0.01
SpliceAI max loss	0.07
REVEL	0.98
AlphaMissense	0.924
CADD Phred	32
SIFT	0
PolyPhen-2	0.998
Grantham distance	142
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).

c.893G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.893G>A
Protein / Detail: p.Ser298Asn
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	25.58
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.841
AlphaMissense	0.596
CADD Phred	29.7
SIFT	0
PolyPhen-2	0.83
Grantham distance	46
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).

c.925G>T

CTNS missense variant

Variant Summary

Nucleotide change: c.925G>T
Protein / Detail: p.Gly309Cys
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	28.95
SpliceAI max gain	0
SpliceAI max loss	0.02
REVEL	0.992
AlphaMissense	0.835
CADD Phred	32
SIFT	0
PolyPhen-2	1
Grantham distance	159
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Sahli, C. et al. Molecular characterization of cystinosis patients: predominance of the CTNS c.829dup mutation in Center Tunisia patients: predominance of the CTNS c.829dup mutation in Center of Tunisia. BMC Genom. Data 27, 25 (2026).

c.926G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.926G>A
Protein / Detail: p.Gly309Asp
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	31.26
SpliceAI max gain	0.01
SpliceAI max loss	0
REVEL	0.974
AlphaMissense	0.974
CADD Phred	32
SIFT	0
PolyPhen-2	1
Grantham distance	94
BLOSUM62	-1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

Explore CTNS Variants

CTNS Variant Map

References

Yeetong, P. et al. Two novel CTNS mutations in cystinosis patients in Thailand.. Gene 499, 323-325 (2012).

c.926G>T

CTNS missense variant

Variant Summary

Nucleotide change: c.926G>T
Protein / Detail: p.Gly309Val
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	31.25
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.983
AlphaMissense	0.906
CADD Phred	31
SIFT	0
PolyPhen-2	1
Grantham distance	109
BLOSUM62	-3

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).

c.943C>T

CTNS nonsense variant

Variant Summary

Nucleotide change: c.943C>T
Protein / Detail: p.Gln315*
Exon / Intron: Exon 11
Variant Type: Nonsense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	42.97
SpliceAI max gain	0
SpliceAI max loss	0.01
CADD Phred	47

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Predicted Translation Product

This nonsense mutation introduces a premature stop codon, so translation halts at this point. The structure below shows only the portion of cystinosin (AlphaFold prediction) that would be translated before the stop codon; everything after it is not shown, since it is never produced. This is an illustrative approximation: a real truncated fragment released on its own may not fold the same way as it does within the full-length protein, and truncated CTNS transcripts/proteins are often degraded by the cell (nonsense-mediated decay) rather than accumulating as a stable fragment.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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CTNS Variant Map

References

Won, J.Y. et al. A case of corneal cystinosis in a patient with rickets and chronic renal failure. Indian J. Ophthalmol. 63, 785-787 (2015).

c.944A>G

CTNS missense variant

Variant Summary

Nucleotide change: c.944A>G
Protein / Detail: p.Gln315Arg
Exon / Intron: Exon 11
Variant Type: Missense
Clinical Manifestation: Unclassified
ClinVar Pathogenicity: Likely Pathogenic
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	30.05
SpliceAI max gain	0
SpliceAI max loss	0
REVEL	0.972
AlphaMissense	0.878
CADD Phred	28.8
SIFT	0
PolyPhen-2	1
BLOSUM62	1

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Sinha, R. et al. Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study. Pediatr. Nephrol. 37, 1811-1836 (2022).

c.1036G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.1036G>A
Protein / Detail: p.Asp346Asn
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Unclassified
ClinVar Pathogenicity: Uncertain Significance
gnomAD: View in gnomAD →

In Silico Predictions

AlphaGenome AVI (Phred)	27.28
SpliceAI max gain	0.04
SpliceAI max loss	0.02
REVEL	0.87
AlphaMissense	0.823
CADD Phred	28.4
SIFT	0
PolyPhen-2	0.985
BLOSUM62	1

Geographic Distribution

This mutation was reported by broad geographic region rather than by individual country; the entire highlighted area shares the same value.

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

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Explore CTNS Gene

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CTNS Variant Map

References

Attard, M. et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum. Mol. Genet. 8, 2507-2514 (1999).

c.1084G>A

CTNS missense variant

Variant Summary

Nucleotide change: c.1084G>A
Protein / Detail: p.Gly362Arg
Exon / Intron: Exon 12
Variant Type: Missense
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Undefined

In Silico Predictions

AlphaGenome AVI (Phred)	27.24
SpliceAI max gain	0.59
SpliceAI max loss	0.02
REVEL	0.861
AlphaMissense	0.195
CADD Phred	28.3
SIFT	0.12
PolyPhen-2	0.281
BLOSUM62	-2

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

Protein Structure

Predicted 3D structure of cystinosin (AlphaFold). The highlighted residue(s) show the position of the original (wild-type) amino acid affected by this mutation — the structure itself is not remodeled to reflect the mutant amino acid.

Loading structure…

Confidence (AlphaFold) Very high Confident Low Very low

Marker color (Clinical Form) Infantile Juvenile Ocular Unclassified / Inconclusive

Explore More

Explore CTNS Gene

Explore CTNS Protein

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CTNS Variant Map

References

Soliman, N.A. et al. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. 14, 87-97 (2014).

c.18_21delGACT

CTNS frameshift deletion variant

Variant Summary

Nucleotide change: c.18_21delGACT
Protein / Detail: p.Thr7Phefs*7
Exon / Intron: Exon 3
Variant Type: Deletion
Clinical Manifestation: Infantile
ClinVar Pathogenicity: Pathogenic

Geographic Distribution

Genomic Location

Position of this variant relative to the CTNS coding sequence.

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Explore CTNS Gene

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CTNS Variant Map

References

Anikster, Y. et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol. Genet. Metab. 66, 111-116 (1999).
Shotelersuk, V. et al. CTNS mutations in an American-based population of cystinosis patients. Am. J. Hum. Genet. 63, 1352-1362 (1998).
Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319-324 (1998).
Emma, F. et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int. 100, 1112-1123 (2021).
Kiehntopf, M. et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum. Mutat. 20, 237 (2002).
Heil, S.G. et al. The molecular basis of Dutch infantile nephropathic cystinosis. Nephron. Nephron 89, 50-55 (2001).
Macías-Vidal, J. et al. Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin. Genet. 76, 486-489 (2009).
Savostyanov, K.V. et al. Genetic Landscape of Nephropathic Cystinosis in Russian Children. Front. Genet. 13, 863157 (2022).
Alcántara-Ortigoza, M.A. et al. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet. Test. 12, 409-414 (2008).
Mason, S. et al. Mutational spectrum of the CTNS gene in Italy. Eur. J. Hum. Genet. 11, 503-508 (2003).
Topaloglu, R. et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr. Nephrol. 27, 115-121 (2012).
Mohammadi Chermahini, Z. et al. CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population. Adv. Biomed. Res. 13, 2 (2024).
Owen, E.P. et al. Common mutation causes cystinosis in the majority of black South African patients. Pediatr. Nephrol. 30, 595-601 (2015).
Ghazi, F. et al. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrologia 37, 301-310 (2017).
Sikora, P. et al. Nephropathic cystinosis in Poland: a 40-year retrospective study. Pol. Arch. Intern. Med. 132, 16320 (2022).
Yeetong, P. et al. Two novel CTNS mutations in cystinosis patients in Thailand.. Gene 499, 323-325 (2012).
Topaloglu, R. et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clin. J. Am. Soc. Nephrol. 12, 1634-1641 (2017).
Zykovich, A. et al. CTNS mutations in publicly-available human cystinosis cell lines. Mol. Genet. Metab. Rep. 5, 63-66 (2015).
Önenli-Mungan, N. et al. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk. J. Pediatr. 58, 362-370 (2016).
Ferreira, F. & Vilarinho, L. CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population. Open J. Genet. 8, 91-100 (2018).
Veys, K. & Zadora, W. et al. Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study. J. Inherit. Metab. Dis. 46, 43-54 (2023).
Shahkarami, S. et al. The first molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran. Nefrologia 33, 308-315 (2013).
Li, X.-Q. et al. The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population. J. Pediatr. Endocrinol. Metab. 32, 375-382 (2019).
Marik, B. et al. Genetic and clinical profile of patients with hypophosphatemic rickets. Eur. J. Med. Genet. 65, 104540 (2022).
Domingo-Gallego, A. et al. Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players. Nephrol. Dial. Transplant. 37, 687-696 (2022).
Vill, K. et al. Neuromuscular conditions and the impact of cystinedepleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients. J. Inherit. Metab. Dis. 45, 183-191 (2022).
Capalbo, A. et al. Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet. 15, e1008409 (2019).
Chau, J.F.T. et al. Comprehensive analysis of recessive carrier status using exome and genome sequencing data in 1543 Southern Chinese. NPJ Genom. Med. 7, 23 (2022).
Al-Haggar, M. et al. A Recent Experience in an Egyptian Medical Center: Strategies for the Clinical and Genetic Diagnoses of Nephropathic Cystinosis. Br. J. Med. Res. 3, 1918-1928 (2013).
Al-Haggar, M. et al. Novel truncating mutation in the CTNS gene in an Egyptian family with cases of infantile nephropathic cystinosis and congenital heart malformations. Middle East J. Med. Genet. 1, 71-75 (2012).
Besouw, M.T.P. et al. Non-invasive measurements of atherosclerosis in adult cystinosis patients. J. Inherit. Metab. Dis. 34, 811-818 (2011).
Rohayem, J. et al. Testicular function in males with infantile nephropathic cystinosis. Hum. Reprod. 36, 1191-1204 (2021).
Doğan, M. et al. Cystinosis in Eastern Turkey. J. Pediatr. Endocrinol. Metab. 29, 965-969 (2016).
Barshop, B.A. et al. Hematopoietic Stem-Cell Gene Therapy for Cystinosis. N. Engl. J. Med. 394, 753-762 (2026).
Conforti, A. et al. Cysteamine treatment restores the in vitro ability to differentiate along the osteoblastic lineage of mesenchymal stromal cells isolated from bone marrow of a cystinotic patient. J. Transl. Med. 13, 143 (2015).
Sinha, R. et al. Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study. Pediatr. Nephrol. 37, 1811-1836 (2022).
Alcántara-Ortigoza, M.A. et al. CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis. J. Pediatr. Genet. 2, 129-132 (2013).
Chiavérini, C. et al. In vivo reflectance confocal microscopy of the skin: A noninvasive means of assessing body cystine accumulation in infantile cystinosis. J. Am. Acad. Dermatol. 68, e111-e116 (2013).
Bengali, M. et al. Non-invasive intradermal imaging of cystine crystals in cystinosis. PLoS ONE 16, e0247846 (2021).
Servais, A. et al. Central nervous system complications in adult cystinosis patients. J. Inherit. Metab. Dis. 43, 348-356 (2020).
Guzzo, I. et al. Radiotherapy-induced hyperthyroidism in a cystinotic kidney transplant patient with Hodgkin lymphoma. Pediatr. Transplant. 15, e56-e59 (2011).
Besouw, M.T.P. et al. Cysteamine Toxicity in Patients with Cystinosis. J. Pediatr. 159, 1004-1011 (2011).
Wilmer, M.J. et al. Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim. Biophys. Acta 1812, 643-651 (2011).
Ivanova, E.A. et al. Ca2+ signalling in human proximal tubular epithelial cells deficient for cystinosin. Cell Calcium 60, 282-287 (2016).
Ivanova, E.A. et al. Cystinosin deficiency causes podocyte damage and loss associated with increased cell motility. Kidney Int. 89, 1037-1048 (2016).

Cystinosis Mutation Database

Cystinosis Mutation Database

223

43

3,566

What is Cystinosis?

Clinical Forms

Infantile Nephropathic

Juvenile Nephropathic

Ocular Non-Nephropathic

Disease Progression Across Life Stages of Untreated Infantile Nephropathic Cystinosis

Mechanisms of cystinosis

Molecular

Cellular

Multisystemic

Diagnosis

Current treatment

Timeline of Key Discoveries

Cystinosis Patient Organizations

Europe

Rest of the World

References

CTNS Gene

Gene Structure & Mutation Map

Coding Sequence & Mutation Map

Gene Details

CTNS Protein Structure

Cystinosin (CTNS) — AlphaFold Predicted Structure

Additional Protein Information

Search CTNS Variants

191

16

7

7

2

Filters

Mutation Explorer

Global Distribution of Published CTNS Alleles

Country

c.1015G>A

Variant Summary

In Silico Predictions

Geographic Distribution

Genomic Location

Protein Structure

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References

c.414G>A

Variant Summary

In Silico Predictions

Geographic Distribution

Genomic Location

Predicted Translation Product

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References

57 kb del.

Variant Summary

Geographic Distribution

Genomic Location

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References

c.681G>A

Variant Summary

In Silico Predictions

Geographic Distribution

Genomic Location

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References

c.198_218del21

Variant Summary

Geographic Distribution

Genomic Location

Protein Structure

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References

c.681+1G>A

Variant Summary

In Silico Predictions

Geographic Distribution

Genomic Location