Search, filter and view detailed variant records

223

Total Variants Listed

43

Countries Registered

3,566

Total Alleles Reported

About the Database

The Cystinosis Mutation Database is designed as a professional research and clinical resource focused on CTNS variation. Users can explore pathogenic, likely pathogenic and other reported variants, review clinical associations, navigate the CTNS gene structure, and access mutation-specific pages containing curated information.

Global Distribution of Reported CTNS Alleles

This database aggregates reported CTNS alleles from around the world. The map below provides a visual overview of international reporting activity and highlights the global reach of cystinosis research and clinical diagnostics.

Global distribution map of reported CTNS alleles

Understanding Cystinosis

Explore the genetics, disease mechanisms, symptoms, diagnosis and treatment of this rare lysosomal storage disorder.

What is Cystinosis?

Cystinosis is a rare inherited disorder caused by disease-causing variants in the CTNS gene. These variants impair production or function of cystinosin, the transporter responsible for moving cystine out of lysosomes. As cystine accumulates, crystals form and progressively damage multiple organs.

Genetic

Autosomal recessive condition caused by CTNS variants. Loss-of-function variants in CTNS impair production or activity of cystinosin, the lysosomal cystine transporter. As transporter function is lost, cystine cannot be efficiently exported from lysosomes and progressively accumulates within cells.

Cellular

Cystine accumulates inside lysosomes causing crystal formation. Intracellular accumulation triggers 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.

Multisystem

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.

Current Standard Therapy: Cysteamine

Cysteamine is the standard disease-modifying therapy for cystinosis. 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.

Pathophysiology of CTNS Deficiency and Cysteamine Therapy

Source: Emma F. et al. Frontiers in Pediatrics (2018). DOI: https://doi.org/10.3389/fped.2018.00058

Infantile Nephropathic

The most severe and common form, typically presenting in infancy with Fanconi syndrome and progressive kidney disease.

Juvenile / Intermediate

Later onset and slower progression with milder renal involvement.

Ocular

Primarily eye involvement with corneal crystal accumulation and photophobia.

Disease Progression Across Life Stages

Image source: Australian Cystinosis Foundation.

Major Clinical Manifestations

Kidneys: Fanconi syndrome, chronic kidney disease and eventual kidney failure.
Eyes: Corneal crystals, photophobia and visual discomfort.
Endocrine System: Growth impairment, hypothyroidism and diabetes.
Muscles: Progressive weakness in adolescence and adulthood.
Nervous System: Neurocognitive and neurological complications in some patients.

Diagnosis

Diagnosis typically combines clinical findings, measurement of leukocyte cystine levels, ophthalmologic examination and molecular analysis of the CTNS gene.

Treatment & Management

Cysteamine therapy remains the cornerstone of treatment and significantly slows disease progression. Patients also require long‑term multidisciplinary monitoring and supportive care for renal, ophthalmologic, endocrine and neuromuscular complications.

Search Mutations

223

Reported Variants

191

Infantile

16

Juvenile

7

Ocular

7

Unclassified

2

Inconclusive

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.

Sort by

Click a mutation name to view its full variant record and reported geographic distribution.

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

Gly339Arg (G339R)

Detailed mutation page.

Variant Overview

Protein change: Gly339Arg (G339R)

Clinical form: Infantile cystinosis

Location: Exon 10 of CTNS

Functional Characterization

This mutant completely lacks cystine transport.
This mutant does not interact with Ragulator/Rag components.
Reported in patients with infantile nephropathic cystinosis.

Gly339Arg Variant Illustration

Illustration of the Gly339Arg (G339R) variant.

Trp138* (W138X)

Detailed mutation page.

Variant Overview

Nucleotide change: c.753G>A

Protein change: p.Trp138*

Variant type: Nonsense

Location: Exon 8 of CTNS

Clinical association: Infantile nephropathic cystinosis.

Reported Information

W138X is a recurrent CTNS nonsense mutation that introduces a premature stop codon and results in truncation of cystinosin. It has been reported in North American and European cystinosis cohorts and is among the most frequently reported CTNS nonsense variants.

This mutation was identified in American-based cystinosis cohorts, where homozygous and compound heterozygous patients were described.

Geographic Distribution

Geographic distribution of the W138X mutation.

57 kb Deletion

Variant Summary

Variant: 57 kb deletion

Database ID: CTNS-MUT-00031

Type: Large genomic deletion

Region Affected: Exons 1–10 of CTNS

Classification: Pathogenic

Overview

This large deletion is one of the best-known disease-causing alterations associated with cystinosis. The deletion removes a substantial portion of the CTNS gene, resulting in loss of normal cystinosin function. Because the affected region includes multiple coding exons, the variant is expected to cause severe disruption of the protein and is therefore classified as pathogenic.

57 kb Deletion Genomic Structure

Geographic distribution of 57 kb deletion variant

Clinical Relevance

Associated with nephropathic cystinosis.
Produces loss of function of the CTNS gene.
Frequently reported in affected individuals.
Useful target for diagnostic and genetic screening assays.

c.del198_218

Detailed mutation page.

Variant Overview

Variant: c.del198_218

Protein change: p.I67_P73

Exon: Exon 5

Type: Deletion

Clinical form: Juvenile

Description

This mutation entry has been configured as a clickable record in the mutation table and opens its own mutation detail page, similar to the 57 kb deletion entry.

c.18_21delGACT

CTNS frameshift deletion variant

Overview

The c.18_21delGACT variant is a four-nucleotide deletion in the CTNS coding sequence. This deletion causes a frameshift and premature termination of translation, resulting in a severely truncated cystinosin protein and loss of normal transporter function. Such early truncating variants are considered pathogenic and are associated with nephropathic cystinosis.

Sequence Context of c.18_21delGACT

Deleted GACT nucleotides highlighted within the CTNS sequence.

Cystinosis Mutation Database

223

43

3,566

About the Database

Global Distribution of Reported CTNS Alleles

Understanding Cystinosis

What is Cystinosis?

Genetic

Cellular

Multisystem

Current Standard Therapy: Cysteamine

Pathophysiology of CTNS Deficiency and Cysteamine Therapy

Infantile Nephropathic

Juvenile / Intermediate

Ocular

Disease Progression Across Life Stages

Major Clinical Manifestations

Diagnosis

Treatment & Management

Search Mutations

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Mutation Explorer

Gly339Arg (G339R)

Variant Overview

Functional Characterization

Gly339Arg Variant Illustration

Geographic Distribution of Gly339Arg

Trp138* (W138X)

Variant Overview

Reported Information

Geographic Distribution

AlphaFold Structural Model

57 kb Deletion

Variant Summary

Overview

57 kb Deletion Genomic Structure

Geographic distribution of 57 kb deletion variant

Clinical Relevance

c.del198_218

Variant Overview

Description

c.18_21delGACT

Overview

Sequence Context of c.18_21delGACT

Geographic Distribution of c.18_21delGACT Variant