CLCNKB (Chloride channel protein ClC-Kb) variants and mutations

CLCNKB (also known as Chloride channel protein ClC-Kb) is a human protein-coding gene encoding a chloride channel protein ClC-Kb protein. It supports chloride reabsorption in the thick ascending limb and distal nephron, helping establish salt balance and the kidney's concentrating gradient. Biallelic loss-of-function variants cause Bartter syndrome type 3 and can sometimes mimic Gitelman syndrome. This analysis covers 1,096 CLCNKB variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes Bartter disease type 3, Bartter syndrome, and Gitelman syndrome. Example CLCNKB variants include E2D, E2K, and E2E.

Variant analysis overview

Gene: CLCNKB
Protein: Chloride channel protein ClC-Kb
UniProt accession: P51801
Organism: Homo sapiens
Variants analyzed: 1096
Variant scope: all variants
Completed: 2026-08-22

Variant and mutation evidence

Variant composition: 913 unspecified-consequence records; 75 missense variants; 80 synonymous variants; 22 frameshift variants; 3 stop-gained variants; 1 in-frame deletions; 2 splice-region variants; 1 substitution
Prediction scores: 860 variants have prediction scores (78% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Bartter disease type 3, Bartter syndrome, Gitelman syndrome, Bartter syndrome type 4, prostate carcinoma, epilepsy, familial focal, with variable foci 1, Proteinuria, Hematuria, autosomal dominant osteopetrosis 1, cardioverter defibrillator, hereditary disease, Sensorineural hearing impairment.

Protein structure and variant hotspots

Protein features: 10 transmembrane segments; 2 domains; 6 binding sites; 1 post-translational modification sites.
Structural context: 512 variants have structural context.
PTM context: 3 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable CLCNKB variants

Examples include E2D, E2K, E2E, E3D, E3K, E3Q, F4L, F4S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

CLCNKB analysis run — CLCNKB (1,096 variants) — completed 2026-08-22