KCND2
Chr 7potassium voltage-gated channel subfamily D member 2
Also known as: KV4.2, RK5
The protein forms voltage-gated potassium channels that regulate neuronal excitability by mediating A-type potassium currents, particularly important for controlling action potential firing patterns and back-propagation in brain neurons. Mutations cause autosomal dominant epileptic encephalopathy, early infantile, and seizures, benign familial infantile, affecting neuronal excitability and seizure threshold. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.574) and has an established GeneReviews entry indicating clinical significance.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
414 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 3 | 18 | 0 | 21 |
Likely Pathogenic | 0 | 5 | 1 | 0 | 6 |
VUS | 13 | 176 | 17 | 3 | 209 |
Likely Benign | 0 | 9 | 28 | 116 | 153 |
Benign | 0 | 1 | 14 | 5 | 20 |
Conflicting | — | 5 | |||
| Total | 13 | 194 | 78 | 124 | 414 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCND2 · 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