KCNS1
Chr 20potassium voltage-gated channel modifier subfamily S member 1
Also known as: Kv9.1, hKv9.1
The KCNS1 protein is a regulatory subunit that modulates the activity of KCNB1 and KCNB2 voltage-gated potassium channels by altering their kinetics and voltage dependencies, playing a critical role in controlling neuronal excitability. Mutations in KCNS1 cause epileptic encephalopathy with onset typically in infancy or early childhood, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.67), reflecting its important role in normal brain function.
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
KCNS1 · 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