KCNMB3

Chr 3

potassium calcium-activated channel subfamily M regulatory beta subunit 3

Also known as: BKBETA3, HBETA3, K(VCA)BETA-3, KCNMB2, KCNMBL, SLO-BETA-3, SLOBETA3

NCBI Gene: 27094 ENSG00000171121 UniProt: Q9NPA1 OMIM: 605222

MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22. [provided by RefSeq, Jul 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.87

Clinical Summary— KCNMB3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 VUS of 48 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.000

Z-score -0.77

OE 1.28 (0.80–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.84Z-score

OE missense 0.80 (0.69–0.94)

112 obs / 139.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.28 (0.80–1.87)

0≤0.351.4

Missense OE?0.80 (0.69–0.94)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 11 / 8.6Missense obs/exp: 112 / 139.9Syn Z: 1.08

This gene — mechanism propensity

0.6840th %ile

GOF

0.6736th %ile

LOF

0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

48 submitted variants in ClinVar

ClinVar

Classification Summary

VUS25

Likely Benign2

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	25	25
Likely Benign	0	2	2
Benign	1	3	4
Total	1	30	31

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap KCNMB3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →