GENE REFERENCE / HGNC:2023

CLCN5

Cl-/H+ antiporter 5

protein-coding geneXp11.23Gene information

What does this gene do?

The CLCN5 gene provides instructions for making a protein that transports charged molecules (ions) across cell membranes. Specifically, the CLCN5 protein exchanges negatively charged chloride ions for positively charged hydrogen ions.

The CLCN5 protein is found primarily in structures called proximal tubules in the kidneys. The proximal tubules help to reabsorb protein and other important substances back into the bloodstream. Substances that are not reabsorbed by the kidneys are released into the urine. Thus, the CLCN5 protein helps prevent protein loss in the urine (proteinuria).

Within proximal tubular cells, the CLCN5 protein is found in specialized compartments called endosomes. Endosomes at the proximal tubular cell surface are involved in the reabsorption of proteins. They also help transport proteins and other molecules to their proper locations within the cell. The process of transporting proteins from the outer cell membrane to the inside of the cell is called endocytosis.

By transporting hydrogen ions into endosomes and chloride ions out, the CLCN5 protein helps endosomes maintain the proper acidity level (pH). Endosomal pH levels must be acidic for the proximal tubular cells to function properly.

Source: MedlinePlus, National Library of Medicine. Source publication: 2026-04-10. Source review: 2026-04.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
Dent disease type 1MONDO:0010225 · Evaluated 2022-07-21	X-linked	DefinitiveTubulopathy Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 859
Submissions for variants in or overlapping this gene: 1,186
Submissions explicitly reporting this gene: 980
Alleles reported pathogenic / likely pathogenic: 171
VariationIDs with uncertain significance: 278
VariationIDs with conflicting classifications: 28

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about CLCN5?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 171 alleles in CLCN5 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in CLCN5.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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