KCNA3
Chr 1potassium voltage-gated channel subfamily A member 3
Also known as: HGK5, HLK3, HPCN3, HUKIII, KV1.3, MK3, PCN3
The protein forms voltage-gated potassium channels that allow nerve cells to repolarize following action potentials and plays an essential role in T-cell proliferation and activation. Mutations cause episodic ataxia type 1, characterized by brief episodes of cerebellar ataxia and continuous muscle rippling (myokymia), with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.89, LOEUF 0.39), indicating that such variants are likely to be pathogenic.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KCNA3 · 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
Metformin for People With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function
RECRUITINGNeoadjuvant Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor
RECRUITINGA Randomized, Parallel-arm, Double Blind, Placebo-controlled Study to Assess the Efficacy of Fampridine for Patients With Spinocerebellar Ataxia SCA27B Caused by a GAA Expansion in the FGF14 Gene
RECRUITINGCreation of a Register of Patients With Neonatal-onset Epileptic Encephalopathy
RECRUITINGSenicapoc and Perampanel for Newly Diagnosed Glioblastoma
RECRUITINGLentiviral Gene Therapy for Epilepsy
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools