CTNS

Chr 17AR

cystinosin, lysosomal cystine transporter

Also known as: CTNS-LSB, PQLC4, SLC66A4

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.806 OMIM phenotypes
Clinical SummaryCTNS
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Gene-Disease Validity (ClinGen)
cystinosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 70 VUS of 200 total submissions
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Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
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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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.000
Z-score 2.23
OE 0.46 (0.280.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.92Z-score
OE missense 1.17 (1.061.29)
271 obs / 231.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.46 (0.280.80)
00.351.4
Missense OE1.17 (1.061.29)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 9 / 19.7Missense obs/exp: 271 / 231.7Syn Z: -1.77
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCTNS-related nephropathic cystinosisLOFAR

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

DN
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

200 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic30
VUS70
Likely Benign36
Benign17
Conflicting8
38
Pathogenic
30
Likely Pathogenic
70
VUS
36
Likely Benign
17
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
1
14
1
38
Likely Pathogenic
24
6
0
0
30
VUS
1
16
52
1
70
Likely Benign
0
0
19
17
36
Benign
0
0
17
0
17
Conflicting
8
Total472310219199

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

View in ClinVar →

Protein Context — Lollipop Plot

CTNS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗