KCNG2
Chr 18potassium voltage-gated channel modifier subfamily G member 2
Also known as: KCNF2, KV6.2
The protein is a regulatory gamma subunit of voltage-gated potassium channels that modulates channel kinetics and voltage-dependent activation when coassembled with other subunits like KCNB1, contributing to cellular excitability regulation including cardiac action potential repolarization. Mutations in KCNG2 cause autosomal dominant epileptic encephalopathy with onset typically in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.67), suggesting some intolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
279 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 | 156 | 0 | 156 |
Likely Pathogenic | 0 | 0 | 7 | 0 | 7 |
VUS | 0 | 83 | 21 | 0 | 104 |
Likely Benign | 0 | 2 | 6 | 2 | 10 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 85 | 190 | 2 | 277 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNG2 · 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 →No open access results found
External Resources
Links to major genomics databases and tools