KCNA4
Chr 11ARpotassium voltage-gated channel subfamily A member 4
Also known as: HBK4, HK1, HPCN2, HUKII, KCNA4L, KCNA8, KV1.4, MCIDDS
KCNA4 encodes a voltage-gated potassium channel that mediates potassium transport in excitable membranes and can form homotetrameric or heterotetrameric channels with other KCNA family members. Autosomal recessive mutations cause a neurodevelopmental disorder characterized by microcephaly, cataracts, intellectual disability, and dystonia with striatal abnormalities. The gene is highly constrained against loss-of-function variants (pLI = 0.98, LOEUF = 0.28), indicating intolerance to functional disruption.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
105 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 | 0 | 22 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 72 | 2 | 0 | 74 |
Likely Benign | 0 | 1 | 0 | 5 | 6 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 73 | 24 | 6 | 103 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNA4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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