KCNH8
Chr 3potassium voltage-gated channel subfamily H member 8
Also known as: ELK, ELK1, Kv12.1, elk3, hElk-1
KCNH8 encodes a pore-forming subunit of a voltage-gated potassium channel that mediates slowly activating, non-inactivating outward potassium currents in response to membrane depolarization. Mutations cause epileptic encephalopathy with developmental delay and intellectual disability, following an autosomal dominant inheritance pattern. The condition typically presents in early childhood with seizures and neurodevelopmental impairment.
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
KCNH8 · 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