KCNS2
Chr 8potassium voltage-gated channel modifier subfamily S member 2
Also known as: KV9.2
The KCNS2 protein is a regulatory subunit that modulates delayed rectifier voltage-gated potassium channels by altering their kinetics and voltage dependencies, forming functional heterotetrameric channels with KCNB1 and KCNB2. Mutations cause autosomal dominant epileptic encephalopathy with onset typically in infancy or early childhood. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.77), suggesting some resilience 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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KCNS2 · 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 →No open access results found
External Resources
Links to major genomics databases and tools