KCNC4
Chr 1potassium voltage-gated channel subfamily C member 4
Also known as: C1orf30, HKSHIIIC, KSHIIIC, KV3.4
The protein is a voltage-gated potassium channel that opens in response to membrane voltage changes and displays rapid activation and inactivation kinetics, which is important for neuronal excitability. Mutations cause progressive sensorineural hearing loss and cerebellar ataxia, inherited in an autosomal dominant pattern. This gene is not highly constrained against loss-of-function variants, and a GeneReviews entry is available for detailed clinical guidance.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KCNC4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools