KCNMB2

Chr 3

potassium calcium-activated channel subfamily M regulatory beta subunit 2

NCBI Gene: 10242 ENSG00000197584 UniProt: Q9NPA1 OMIM: 605214

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 decreases the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants of this gene. Additional variants are discussed in the literature, but their full length nature has not been described. [provided by RefSeq, Jul 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.57

Clinical Summary— KCNMB2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.

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ClinVar Variants

23 VUS of 30 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.554

Z-score 2.51

OE 0.18 (0.07–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.86Z-score

OE missense 0.79 (0.67–0.93)

103 obs / 130.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.07–0.57)

0≤0.351.4

Missense OE?0.79 (0.67–0.93)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 2 / 11.0Missense obs/exp: 103 / 130.6Syn Z: -0.01

This gene — mechanism propensity

0.6162th %ile

GOF

0.6638th %ile

LOF

0.3551th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

30 submitted variants in ClinVar

ClinVar

Classification Summary

VUS23

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	23	0	23
Likely Benign	0	1	1
Benign	0	1	1
Total	23	2	25

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap KCNMB2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →