KCNQ2 (O43526) variants and mutations

KCNQ2 (also known as O43526) is a human protein-coding gene encoding a potassium voltage-gated channel subfamily KQT member 2 protein. Together with KCNQ3, its slowly activating potassium current provides much of the neuronal M-current that suppresses repetitive firing. Pathogenic variants cause a spectrum from self-limited familial neonatal epilepsy to severe developmental and epileptic encephalopathy. This analysis covers 1,802 KCNQ2 variants and mutations. Of these, 27% have pathogenic or likely pathogenic clinical classifications, 84% have computational variant effect predictions from REVEL and MutPred, and 38% have population-specific frequency data. Disease context includes Benign familial neonatal seizures, seizures, benign familial neonatal, 1, and genetic developmental and epileptic encephalopathy. Example KCNQ2 variants include M1I, M1K, and M1L.

Variant analysis overview

Gene: KCNQ2
Protein: O43526
UniProt accession: O43526
Organism: Homo sapiens
Variants analyzed: 1802
Variant scope: all variants
Completed: 2026-08-10

Variant and mutation evidence

Variant composition: 1,444 unspecified-consequence records; 2 stop retained variant; 5 stop lost; 8 stop-gained variants; 217 missense variants; 106 synonymous variants; 15 frameshift variants; 3 in-frame deletions; 2 substitution
Clinical classifications: 486 pathogenic or likely pathogenic; 73 benign or likely benign; 512 uncertain-significance; 149 other clinical labels.
Computational signals: 212 REVEL high-risk; 190 MutPred high-risk.
Variant classes: 1,603 missense; 106 synonymous; 85 truncating or splice.
Prediction scores: 1,519 variants have prediction scores (85% of the analyzed set).
Literature: 31 publications are represented in the literature summary.

Clinical, disease, and population context

Clinical evidence: 146 records have expert-only or criteria-backed evidence.
Clinical annotations: 1,230 variants have clinical annotations.
Population evidence: 1,109 variants have population-frequency evidence.
Disease context: 25 disease associations are represented. Top associations: Benign familial neonatal seizures, seizures, benign familial neonatal, 1, genetic developmental and epileptic encephalopathy, Seizure, Epileptic encephalopathy, early-infantile DEE, hereditary disease, BFNS1, DEE7.

Protein structure and variant hotspots

Protein features: 6 transmembrane segments; 3 binding sites; 11 post-translational modification sites.
Ancestry evidence: 693 variants have ancestry-specific frequency data.
Structural context: 227 variants have structural context.
PTM context: 14 variants overlap post-translational modification sites.
3D hotspots: 1 hotspot clusters were identified. Clusters at residues 210-216 (intolerant, 12 variants).
Allosteric analysis: 9 functional sites were identified.
gnomAD gene constraint: pLI 1.00 (highly intolerant of loss-of-function variation); LOEUF 0.17; missense Z-score 5.61.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, LitVar.

Notable KCNQ2 variants

Examples include M1I, M1K, M1L, M1T, M1V, V2G, V2M, Q3E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

KCNQ2 analysis run — KCNQ2 (1,802 variants) — completed 2026-08-10