CTNS

Chr 17AR

cystinosin, lysosomal cystine transporter

Also known as: CTNS-LSB, PQLC4, SLC66A4

NCBI Gene: 1497 ENSG00000040531 UniProt: O60931

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]

Primary Disease Associations & Inheritance

Cystinosis, atypical nephropathicMIM #219800

Cystinosis, late-onset juvenile or adolescent nephropathicMIM #219900

Cystinosis, nephropathicMIM #219800

Cystinosis, ocular nonnephropathicMIM #219750

Cystinosis, nephropathicMIM #219800

Cystinosis, atypical nephropathicMIM #219800

UniProtCystinosis, adult, non-nephropathic type

387

ClinVar variants

123

Pathogenic / LP

0.00

pLI score

Active trials

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

123 Pathogenic / Likely Pathogenic· 91 VUS of 387 total submissions

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Clinical Trials

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.80LOEUF

pLI 0.000

Z-score 2.23

OE 0.46 (0.28–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.92Z-score

OE missense 1.17 (1.06–1.29)

271 obs / 231.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.46 (0.28–0.80)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (1.06–1.29)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.23

0≤1.21.6

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

ClinVar Variant Classifications

387 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70

Likely Pathogenic53

VUS91

Likely Benign158

Benign9

Conflicting6

Pathogenic

Likely Pathogenic

VUS

158

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	6	52	0	70
Likely Pathogenic	29	7	17	0	53
VUS	1	62	24	4	91
Likely Benign	1	7	82	68	158
Benign	0	0	7	2	9
Conflicting	—				6
Total	43	82	182	74	387

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.

Gene2Phenotype Curations

CTNS-related nephropathic cystinosis

definitive

ARLoss Of FunctionAbsent Gene Product

Dev. DisordersEyeSkin

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

CYSTINOSIN; CTNS

MIM #606272 · *

Cystinosis, atypical nephropathic

MIM #219800