CLCNKB
Chloride Voltage-Gated Channel Kb
Gene Information Card
| Symbol | CLCNKB |
|---|---|
| Full Name | Chloride Voltage-Gated Channel Kb |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 1185 ncbi.nlm.nih.gov/gene/1185 |
| Ensembl ID | ENSG00000184908 |
| UniProt ID | P51801 |
| OMIM ID | 602023 |
| HGNC ID | 2027 |
| Aliases | ClC-Kb, ClC-K2 |
Description
CLCNKB encodes the chloride voltage-gated channel Kb (ClC-Kb), a member of the ClC family of chloride channels. This protein is primarily expressed in the kidney, where it mediates chloride reabsorption in the thick ascending limb of Henle's loop and distal nephron. Mutations in CLCNKB cause Bartter syndrome type 3, an autosomal recessive renal tubular disorder characterized by salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bartter syndrome type 3 | Loss-of-function mutations impair chloride reabsorption in the thick ascending limb, leading to salt wasting and electrolyte disturbances. | OMIM #607364; ClinVar pathogenic variants |
| Bartter syndrome with sensorineural deafness | Compound heterozygous or homozygous mutations may also affect hearing due to ClC-Kb expression in the inner ear. | OMIM #602023; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 42.5 | High |
| Inner ear | 12.3 | Medium |
| Testis | 3.1 | Low |
| Brain | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.5 | Low expression |
| HK-2 (kidney proximal tubule) | 15.2 | Moderate |
| MDCK | 8.7 | Moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.128G>A (p.Trp43*) | Nonsense | <0.1% | Loss of function; premature truncation |
| c.416C>T (p.Thr139Met) | Missense | 0.2% | Impaired channel conductance |
| c.1058delC (p.Pro353Leufs*12) | Frameshift | <0.1% | Loss of function; protein truncation |
Mutation functional classification
Loss of Function (LOF)
Most CLCNKB mutations result in loss of chloride channel activity, leading to Bartter syndrome type 3.
Gain of Function (GOF)
Not reported for CLCNKB.
Dominant Negative (DN)
Not reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity (GO:0005247) | • chloride transport (GO:0006821) |
| • potassium ion import (GO:0010107) | • calcium ion transmembrane transport (GO:0070588) |
| • plasma membrane (GO:0005886) |
Pathways
• Renal tubular ion transport (Reactome: R-HSA-549127)
• Chloride channelopathies (KEGG: hsa04964)
Protein Summary
The ClC-Kb protein is a 687-amino acid transmembrane chloride channel that forms homodimers. It requires the accessory subunit barttin (BSND) for proper trafficking and function. In the kidney, ClC-Kb mediates basolateral chloride efflux in the thick ascending limb, enabling sodium reabsorption and urine concentration. Defects lead to Bartter syndrome type 3.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCNKB Knockout HEK293 Cell Line | EDJ-KQ4287 | Human | 1188 | Details Get a Quote |
| CLCNKB Knockout HeLa Cell Line | EDJ-KQ52926 | Human | 1188 | Details Get a Quote |
| CLCNKB Knockout A-549 Cell Line | EDJ-KQ61393 | Human | 1188 | Details Get a Quote |
| CLCNKB Knockout HCT 116 Cell Line | EDJ-KQ69888 | Human | 1188 | Details Get a Quote |
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