KCNMB3
protein-codingpotassium calcium-activated channel subfamily M regulatory beta subunit 3, 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 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]
- KCNMB2
- KCNMBL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.3 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 KCNMB3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_171830.2. 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 | 27 | 1 | 1 | 29 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 30 | 1 | 1 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_741981.1 | 3 | MANE Select | |
| Ensembl | ENSP00000376451.2 | 3 | MANE Select | |
| RefSeq | NP_001157149.1 | 4 | Standard | |
| RefSeq | NP_055222.3 | 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
- potassium ion transmembrane transport
Molecular Function
- 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
- ENST00000314235
- Coding exons
- 4
- Length
- 27261
- Individuals with no LoFs
- 125619
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 127
- Defined
- 125747
- p
- 0.000509
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.837 | 112 | 140 | 0.801 | 0.00000677 | 1845 |
| Missense (PolyPhen) | 34 | 43.907 | 0.77437 | 608 | ||
| Synonymous | 1.08 | 44 | 54.1 | 0.813 | 0.00000290 | 525 |
| Loss of Function | -0.770 | 11 | 8.57 | 1.28 | 4.49e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0053 | 0.0053 | notable |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00089 | 0.00089 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00039 | 0.00036 | rare |
| Other | 0.00033 | 0.00033 | 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. Alters the functional properties of the current expressed by the KCNMA1 channel. Isoform 2, isoform 3 and isoform 4 partially inactivate the current of KCNBMA. Isoform 4 induces a fast and incomplete inactivation of KCNMA1 channel that is detectable only at large depolarizations. In contrast, isoform 1 does not induce detectable inactivation of KCNMA1. Two or more subunits of KCNMB3 are required to block the KCNMA1 tetramer. {ECO:0000269|PubMed:10766764, ECO:0000269|PubMed:10864947}.;
Recessive Scores
- pRec
- 0.0686
Intolerance Scores
- LoFtool
- 0.998
- RVIS EVS
- 1.77
- RVIS percentile EVS
- 96.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.000180
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |