KCNF1
Chr 2potassium voltage-gated channel modifier subfamily F member 1
Also known as: IK8, KCNF, KV5.1, kH1
The protein functions as a regulatory alpha-subunit of voltage-gated potassium channels that modulates the expression and gating kinetics of KCNB1 and KCNB2 channels by affecting deactivation and inactivation processes. Mutations in KCNF1 cause early infantile epileptic encephalopathy, an autosomal recessive disorder characterized by seizure onset in the first months of life. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.66), and the severe early-onset neurological phenotype reflects the critical role of potassium channel regulation in neuronal excitability.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Highly missense-constrained (top ~0.1%)
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
KCNF1 · 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