CLCNKA: Chloride Voltage-Gated Channel Ka
Key regulator of renal chloride transport and blood pressure homeostasis
Gene Information Card
| Symbol | CLCNKA |
|---|---|
| Full Name | Chloride Voltage-Gated Channel Ka |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 1187 ncbi.nlm.nih.gov/gene/1187 |
| Ensembl ID | ENSG00000186510 |
| UniProt ID | P51800 |
| OMIM ID | 602024 |
| HGNC ID | 2026 |
| Aliases | CLC-Ka, CLCK1, ClC-K1 |
Description
CLCNKA encodes a member of the voltage-gated chloride channel (CLC) family, specifically the chloride channel Ka (ClC-Ka). This protein is predominantly expressed in the kidney, where it mediates transepithelial chloride transport in the thin ascending limb of Henle's loop and the inner medullary collecting duct. ClC-Ka functions as a homodimer and requires the accessory subunit barttin (BSND) for proper trafficking and channel activity. Mutations in CLCNKA cause Bartter syndrome type 4b, a renal salt-wasting disorder characterized by hypokalemic alkalosis, hypercalciuria, and sensorineural deafness when combined with mutations in CLCNKB.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bartter syndrome type 4b | Loss-of-function mutations in CLCNKA impair chloride reabsorption in the kidney, leading to salt wasting and electrolyte imbalance. Co-inheritance with CLCNKB mutations causes deafness due to disrupted chloride transport in the inner ear. | ClinVar, OMIM |
| Bartter syndrome type 4 (with CLCNKB) | Compound heterozygous or digenic mutations in CLCNKA and CLCNKB abolish ClC-Ka/ClC-Kb function, causing severe antenatal Bartter syndrome with sensorineural deafness. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 45.2 | High |
| Testis | 1.8 | Low |
| Liver | 0.5 | Not detected |
| Brain | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 0.1 | Low expression; used for heterologous expression studies |
| HK-2 (kidney proximal tubule) | 12.4 | Moderate expression |
| MDCK | 8.7 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.416G>A (p.Arg139His) | Missense | Rare | Loss of function; associated with Bartter syndrome type 4b |
| c.143C>T (p.Thr48Met) | Missense | Rare | Impaired channel activity; reported in Bartter syndrome |
| c.919G>A (p.Gly307Arg) | Missense | Rare | Reduced chloride conductance; pathogenic in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Most CLCNKA mutations are loss-of-function, reducing or abolishing chloride channel activity, leading to renal salt wasting.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLCNKA.
Dominant Negative (DN)
No dominant-negative effects have been described; mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity (GO:0005247) | • chloride transmembrane transport (GO:1902476) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
| • ion channel complex (GO:0034702) |
Pathways
• Chloride transport (Reactome: R-HSA-983712)
• Transport of inorganic cations/anions (Reactome: R-HSA-425393)
• Bartter syndrome (KEGG: hsa04960)
Protein Summary
The CLCNKA protein (ClC-Ka) is a 687-amino acid voltage-gated chloride channel with 13 transmembrane domains. It forms homodimers and requires the beta-subunit barttin (BSND) for membrane localization and function. ClC-Ka is essential for chloride reabsorption in the thin ascending limb of Henle's loop and contributes to urinary concentration. Its structure includes a selectivity filter for chloride ions and a gating mechanism regulated by voltage and pH.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCNKA Knockout HEK293 Cell Line | EDJ-KQ4289 | Human | 1187 | Details Get a Quote |
| CLCNKA Knockout HeLa Cell Line | EDJ-KQ52925 | Human | 1187 | Details Get a Quote |
| CLCNKA Knockout A-549 Cell Line | EDJ-KQ61392 | Human | 1187 | Details Get a Quote |
| CLCNKA Knockout HCT 116 Cell Line | EDJ-KQ69887 | Human | 1187 | Details Get a Quote |
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