KCNMB2
protein-codingpotassium calcium-activated channel subfamily M regulatory beta subunit 2, the group of Potassium calcium-activated channel subfamily M regulatory beta subunits
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~571.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KCNMB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181361.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 23 | 23 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 26 | 1 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_852006.1 | 4 | MANE Select | |
| Ensembl | ENSP00000397483.1 | 4 | MANE Select | |
| RefSeq | NP_001265840.1 | 4 | Standard | |
| RefSeq | NP_005823.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vascular smooth muscle contraction - Homo sapiens (human)
- cGMP-PKG signaling pathway - Homo sapiens (human)
- Insulin secretion - Homo sapiens (human)
- Neuronal System
- Hemostasis
Biological Process
- action potential
- detection of calcium ion
- potassium ion transport
- neuronal action potential
- regulation of vasoconstriction
Molecular Function
- ion channel inhibitor activity
- calcium-activated potassium channel activity
- potassium channel regulator activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- voltage-gated potassium channel complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000432997
- Coding exons
- 4
- Length
- 571498
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125739
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.858 | 103 | 131 | 0.789 | 0.00000677 | 1549 |
| Missense (PolyPhen) | 41 | 58.181 | 0.70469 | 691 | ||
| Synonymous | -0.00969 | 50 | 49.9 | 1.00 | 0.00000271 | 449 |
| Loss of Function | 2.51 | 2 | 11.0 | 0.182 | 5.49e-7 | 129 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00060 | 0.00060 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Acts as a negative regulator that confers rapid and complete inactivation of KCNMA1 channel complex. May participate in KCNMA1 inactivation in chromaffin cells of the adrenal gland or in hippocampal CA1 neurons. {ECO:0000269|PubMed:10097176, ECO:0000269|PubMed:10377337}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.415
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.174
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |