CTNS

Chr 17AR

cystinosin, lysosomal cystine transporter

Also known as: CTNS-LSB, PQLC4, SLC66A4

NCBI Gene: 1497 ENSG00000040531 UniProt: O60931 OMIM: 606272

The protein encoded by this gene functions as a seven-transmembrane domain transporter that moves cystine out of lysosomes using the lysosomal membrane's H+ electrochemical gradient. Mutations cause cystinosis, a lysosomal storage disorder with multiple phenotypes including nephropathic, late-onset juvenile/adolescent nephropathic, atypical nephropathic, and ocular nonnephropathic forms, inherited in an autosomal recessive pattern. Loss of cystine transport function leads to pathogenic cystine accumulation within lysosomes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a seven-transmembrane domain protein that functions to transport cystine out of lysosomes. Its activity is driven by the H+ electrochemical gradient of the lysosomal membrane. Mutations in this gene cause cystinosis, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.806 OMIM phenotypes

Clinical Summary— CTNS

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Gene-Disease Validity (ClinGen)

cystinosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

221 unique Pathogenic / Likely Pathogenic· 262 VUS of 937 total submissions

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Clinical Trials

5 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CTNS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.23

OE 0.46 (0.28–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.92Z-score

OE missense 1.17 (1.06–1.29)

271 obs / 231.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.46 (0.28–0.80)

0≤0.351.4

Missense OE?1.17 (1.06–1.29)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 9 / 19.7Missense obs/exp: 271 / 231.7Syn Z: -1.77

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCTNS-related nephropathic cystinosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.78top 25%

GOF

0.7127th %ile

LOF

0.2484th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

937 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic107

Likely Pathogenic114

VUS262

Likely Benign335

Benign72

Conflicting33

107

Pathogenic

114

Likely Pathogenic

262

VUS

335

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	62	13	31	1	107
Likely Pathogenic	79	25	10	0	114
VUS	2	166	89	5	262
Likely Benign	2	9	158	166	335
Benign	0	3	65	4	72
Conflicting	—				33
Total	145	216	353	176	923

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

68 pathogenic / likely-pathogenic (of 111) ClinVar copy-number / structural variants overlap CTNS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →