CLCN5

Chr XXLR

Cl-/H+ antiporter 5

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

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]

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
3
Active trials
18
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.28
LOEUF· LoF intol.
Mechanism
Clinical SummaryCLCN5
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Gene-Disease Validity (ClinGen)
Dent disease type 1 · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.992
Z-score 4.36
OE 0.11 (0.050.28)
Highly constrained

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

Missense Constraint
2.53Z-score
OE missense 0.60 (0.540.68)
195 obs / 323.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.11 (0.050.28)
00.351.4
Missense OE0.60 (0.540.68)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 3 / 27.8Missense obs/exp: 195 / 323.2Syn Z: 1.59

ClinVar Variant Classifications

0 submitted variants in 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.

Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Dent Disease.
Adam MP et al.
2017Review
Update on Dent Disease.
Ehlayel AM et al.·Pediatr Clin North Am
2019Review
Top 5 results · since 2015Search PubMed ↗