KCNK1
Chr 1potassium two pore domain channel subfamily K member 1
Also known as: DPK, HOHO, K2P1, K2p1.1, KCNO1, TWIK-1, TWIK1
The protein encoded by this gene forms potassium channels that regulate resting membrane potential and neuronal excitability in brain astrocytes and other tissues, functioning primarily as heterodimers with other potassium channel subunits. Pathogenic variants in KCNK1 cause autosomal dominant epilepsy with febrile seizures plus (EFSP) and focal epilepsy, typically with childhood onset. The gene shows tolerance to loss-of-function variants (pLI 0.03, LOEUF 0.91), suggesting the pathogenic mechanism may not involve simple 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
KCNK1 · 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