KCNA10

Chr 1

potassium voltage-gated channel subfamily A member 10

Also known as: Kcn1, Kv1.8

The KCNA10 protein functions as a voltage-gated potassium channel that selectively allows potassium ion flow across excitable membranes in response to voltage changes. Mutations in this gene cause autosomal dominant epileptic encephalopathy, early infantile, 32, characterized by seizure onset in infancy and developmental impairment. The gene shows low constraint to loss-of-function variation (pLI 0.0008, LOEUF 1.224), suggesting tolerance to protein-truncating variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.22
Clinical SummaryKCNA10
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.22LOEUF
pLI 0.001
Z-score 1.09
OE 0.62 (0.341.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.82Z-score
OE missense 1.14 (1.041.25)
327 obs / 287.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.62 (0.341.22)
00.351.4
Missense OE1.14 (1.041.25)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 6 / 9.7Missense obs/exp: 327 / 287.8Syn Z: -0.65
DN
0.83top 10%
GOF
0.85top 5%
LOF
0.1993th %ile

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.

GOFprediction above median
DNprediction above median

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

KCNA10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC