KCNA6
Chr 12potassium voltage-gated channel subfamily A member 6
Also known as: HBK2, KV1.6, PPP1R96
KCNA6 encodes a voltage-gated potassium channel that forms tetrameric channels regulating potassium transport and neuronal excitability in the nervous system. Mutations cause early infantile epileptic encephalopathy with developmental delay, seizures, and intellectual disability, following an autosomal dominant inheritance pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.526), and the associated epileptic encephalopathy typically presents in infancy.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
153 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 2 | 52 | 0 | 54 |
Likely Pathogenic | 0 | 1 | 5 | 0 | 6 |
VUS | 1 | 75 | 9 | 0 | 85 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 80 | 66 | 0 | 147 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNA6 · 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