KCNMA1

Chr 10

potassium calcium-activated channel subfamily M alpha 1

Also known as: BKTM, CADEDS, IEG16, KCa1.1, LIWAS, MaxiK, PNKD3, SAKCA

NCBI Gene: 3778ENSG00000156113UniProt: Q12791

This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtParoxysmal non-kinesigenic dyskinesia 3 with or without generalized epilepsy
UniProtEpilepsy, idiopathic generalized 16
UniProtCerebellar atrophy, developmental delay, and seizures
UniProtLiang-Wang syndrome

Clinical highlights

Gene-disease validity (ClinGen)
generalized epilepsy-paroxysmal dyskinesia syndrome · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Both gain of function and loss of function mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
57
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.28
LOEUF· LoF intol.
GOF/LOF*
Mechanism· annotated
📖
GeneReview available — KCNMA1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.28LOEUF
pLI 0.997
Z-score 6.08
OE 0.16 (0.10–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
5.06Z-score
OE missense 0.46 (0.41–0.50)
311 obs / 683.4 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.16 (0.10–0.28)
0≤0.351.4
Missense OE?0.46 (0.41–0.50)
0≤0.61.4
Synonymous OE?1.18
0≤1.21.6
LoF obs/exp: 10 / 61.5Missense obs/exp: 311 / 683.4Syn Z: -2.35

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KCNMA1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients