CLCN5

Chr XXLR

Cl-/H+ antiporter 5

Also known as: CLC5, CLCK2, ClC-5, DENT1, DENTS, NPHL1, NPHL2, XLRH

NCBI Gene: 1184ENSG00000171365UniProt: P51795OMIM: 300008

This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Dent disease 1MIM #300009
XLR
Hypophosphatemic ricketsMIM #300554
XLR
Nephrolithiasis, type IMIM #310468
XLR
Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosisMIM #308990
XLR
UniProtNephrolithiasis, X-linked recessive, with renal failure

Clinical highlights

Gene-disease validity (ClinGen)
Dent disease type 1 · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
3
Active trials
30
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.28
LOEUF· LoF intol.
—
Mechanism
📖
GeneReview available — CLCN5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.28LOEUF
pLI 0.992
Z-score 4.36
OE 0.11 (0.05–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.53Z-score
OE missense 0.60 (0.54–0.68)
195 obs / 323.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.11 (0.05–0.28)
0≤0.351.4
Missense OE?0.60 (0.54–0.68)
0≤0.61.4
Synonymous OE?0.81
0≤1.21.6
LoF obs/exp: 3 / 27.8Missense obs/exp: 195 / 323.2Syn Z: 1.59

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CLCN5 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients