KCNA5
Chr 12ADpotassium voltage-gated channel subfamily A member 5
Also known as: ATFB7, HCK1, HK2, HPCN1, KV1.5, PCN1
KCNA5 encodes a voltage-gated potassium channel that forms tetrameric channels mediating potassium transport across excitable membranes and regulating membrane potential in cardiac and pancreatic cells. Mutations cause familial atrial fibrillation type 7, a cardiac arrhythmia disorder with autosomal dominant inheritance. The gene shows low constraint against loss-of-function variants (pLI 0.001, LOEUF 0.919), suggesting tolerance to heterozygous inactivation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
564 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 | 1 | 2 | 49 | 0 | 52 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 16 | 292 | 17 | 34 | 359 |
Likely Benign | 0 | 10 | 3 | 93 | 106 |
Benign | 0 | 1 | 6 | 7 | 14 |
Conflicting | — | 28 | |||
| Total | 17 | 305 | 79 | 134 | 563 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNA5 · 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