CLCN5
Chloride Voltage-Gated Channel 5
Gene Information Card
| Symbol | CLCN5 |
|---|---|
| Full Name | Chloride Voltage-Gated Channel 5 |
| Gene Type | protein-coding |
| Chromosomal Location | Xp11.23-p11.22 |
| NCBI Gene ID | 1184 ncbi.nlm.nih.gov/gene/1184 |
| Ensembl ID | ENSG00000171365 |
| UniProt ID | P51795 |
| OMIM ID | 300008 |
| HGNC ID | 2023 |
| Aliases | CLC5, ClC-5, DENT1, NPHL2, XRNephrolithiasis |
Description
The CLCN5 gene encodes a member of the ClC family of voltage-gated chloride channels. The encoded protein, ClC-5, is primarily expressed in the kidney, where it localizes to endosomes and plays a critical role in endosomal acidification and receptor-mediated endocytosis. Mutations in CLCN5 cause Dent disease 1, an X-linked disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and progressive renal failure.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dent disease 1 | Loss-of-function mutations impair endosomal acidification, disrupting protein reabsorption in proximal tubules. | ClinVar, OMIM |
| Nephrolithiasis, X-linked | Defective chloride transport leads to hypercalciuria and calcium stone formation. | OMIM |
| Low-molecular-weight proteinuria | Impaired endocytosis of filtered proteins due to defective ClC-5 function. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Small intestine | 3.2 | Medium |
| Liver | 1.8 | Low |
| Brain | 0.9 | Low |
| Testis | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 8.1 | Moderate expression |
| HK-2 (kidney proximal tubule) | 15.3 | High expression |
| HepG2 | 2.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2002C>T (p.Arg648* ) | Nonsense | Rare | Premature stop, loss of function |
| c.221G>A (p.Arg74His) | Missense | Rare | Impaired channel activity |
| c.1437+1G>A | Splice site | Rare | Splicing defect, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most CLCN5 mutations result in loss of chloride channel function, leading to Dent disease 1.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; disease is X-linked recessive.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity | • chloride transmembrane transport |
| • endosomal acidification | • receptor-mediated endocytosis |
| • protein homodimerization activity |
Pathways
• Endosomal acidification
• Chloride transport
• Receptor-mediated endocytosis in proximal tubule
Protein Summary
ClC-5 is a 746-amino-acid voltage-gated chloride channel that forms homodimers and localizes to early endosomes. It facilitates chloride influx to neutralize proton pump activity, enabling endosomal acidification essential for protein reabsorption in kidney proximal tubules. Mutations disrupt this process, causing Dent disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCN5 Knockout HEK293 Cell Line | EDJ-KQ2995 | Human | 1184 | Details Get a Quote |
| CLCN5 Knockout A-549 Cell Line | EDJ-KQ24186 | Human | 1184 | Details Get a Quote |
| CLCN5 Knockout HCT 116 Cell Line | EDJ-KQ24187 | Human | 1184 | Details Get a Quote |
| CLCN5 Knockout HeLa Cell Line | EDJ-KQ18239 | Human | 1184 | Details Get a Quote |
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