KCNA10

Chr 1

potassium voltage-gated channel subfamily A member 10

Also known as: Kcn1, Kv1.8

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It is specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. This gene is intronless, and the gene is clustered with genes KCNA2 and KCNA3 on chromosome 1. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.22
Clinical SummaryKCNA10
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
85 VUS of 92 total submissions

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 OE?0.62 (0.341.22)
00.351.4
Missense OE?1.14 (1.041.25)
00.61.4
Synonymous OE?1.08
01.21.6
LoF obs/exp: 6 / 9.7Missense obs/exp: 327 / 287.8Syn Z: -0.65

This gene — mechanism propensity

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

92 submitted variants in ClinVar

Classification Summary

VUS85
Likely Benign2
Benign5
85
VUS
2
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
85
0
0
85
Likely Benign
0
2
0
0
2
Benign
0
3
0
2
5
Total0900292

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap KCNA10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

KCNA10 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →