KCNMB4 potassium calcium-activated channel subfamily M regulatory beta subunit 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNMB4provided by HGNC
Official Full Name: potassium calcium-activated channel subfamily M regulatory beta subunit 4provided by HGNC
Primary source: HGNC:HGNC:6289
See related: Ensembl:ENSG00000135643 MIM:605223; AllianceGenome:HGNC:6289
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
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 slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit. [provided by RefSeq, Jul 2008]
Expression: Broad expression in brain (RPKM 7.6), adrenal (RPKM 4.7) and 15 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 12q15

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (70366290..70434292)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (70345760..70413761)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (70760070..70828072)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Family-Based Cohort Association Study of PRKCB1, CBLN1 and KCNMB4 Gene Polymorphisms and Autism in Polish Population.
Title: Family-Based Cohort Association Study of PRKCB1, CBLN1 and KCNMB4 Gene Polymorphisms and Autism in Polish Population.
This study presents cryo-EM structures of Slo1 in complex with the auxiliary protein, beta4. Four beta4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane.
Title: Molecular structures of the human Slo1 K(+) channel in complex with β4.
Two recurrent fusion genes associated with the 12q locus, LRP1-SNRNP25 and KCNMB4-CCND3, were by RT-PCR, Sanger sequencing and FISH, and were found to be osteosarcoma specific in a validation cohort of 240 other sarcomas.
Title: Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma.
Recombinant martentoxin selectively blocks KCNMA1/KCNMB4 channels.
Title: Recombinant expression and functional characterization of martentoxin: a selective inhibitor for BK channel (α + β4).
BK channel beta4 subunit influences sensitivity and tolerance to alcohol by altering its response to kinases
Title: Large conductance voltage- and Ca2+-gated potassium (BK) channel β4 subunit influences sensitivity and tolerance to alcohol by altering its response to kinases.
Study shows that beta4 subunit of the MaxiK channel has no potential endocytic signal and 2 specific amino acids in the functional basic motif retention/retrieval trafficking signal at the C-terminus may play a role in controlling cellular excitability
Title: An endoplasmic reticulum trafficking signal regulates surface expression of β4 subunit of a voltage- and Ca²⁺-activated K⁺ channel.
IFN-gamma changed mRNA levels of the BK beta-modulatory proteins KCNMB2 (increased) and KCNMB4 (decreased) as well as leucine-rich repeat-containing protein (LRRC)26 (decreased).
Title: IFN-γ-mediated reduction of large-conductance, Ca2+-activated, voltage-dependent K+ (BK) channel activity in airway epithelial cells leads to mucociliary dysfunction.
our data suggest that the rs398702 variant in the KCNMB4 gene is unlikely to influence significantly the risk of developing mesial temporal lobe epilepsy or its severity
Title: Failure to confirm association of a polymorphism in KCNMB4 gene with mesial temporal lobe epilepsy.
These results suggest that fast-gating, type I BK channels lacking beta4 can increase neuronal excitability in response to reduced phosphatase activity and activation of calcium channels.
Title: Modulation by the BK accessory β4 subunit of phosphorylation-dependent changes in excitability of dentate gyrus granule neurons.
results argue that, for native mouse Slo3 channels, the beta4 subunit must be considered as a potential interaction partner and, furthermore, that KCNMB subunits may have functions unrelated to regulation of the Slo1 alpha subunit
Title: Interactions between beta subunits of the KCNMB family and Slo3: beta4 selectively modulates Slo3 expression and function.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 from both CCR5- and CXCR4-tropic HIV-1 strains opens calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages; these signals are mediated by CCR5 and CXCR4	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

WI-22339 (e-PCR)
- UniSTS:55041

D11S2921 (e-PCR)
- UniSTS:152074

RH94337 (e-PCR)
- UniSTS:87566

A004H24 (e-PCR)
- UniSTS:63009

SHGC-173523 (e-PCR)
- UniSTS:185384

G20451 (e-PCR)
- UniSTS:62000

G20225 (e-PCR)
- UniSTS:3633

A005R39 (e-PCR)
- UniSTS:62001

A005A38 (e-PCR)
- UniSTS:3634

RH103017 (e-PCR)
- UniSTS:97351

WI-12177 (e-PCR)
- UniSTS:76655

G63695 (e-PCR)
- UniSTS:140657

BCD1535 (e-PCR)
- UniSTS:78981

D11S3114 (e-PCR)
- UniSTS:152207

KCNMB4_893 (e-PCR)
- UniSTS:277432

KCNMB4_V186 (e-PCR)
- UniSTS:277432

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium-activated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-activated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium channel regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in action potential	IDA Inferred from Direct Assay more info	PubMed
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in detection of calcium ion	IBA Inferred from Biological aspect of Ancestor more info
involved_in detection of calcium ion	IDA Inferred from Direct Assay more info	PubMed
involved_in neuronal action potential	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of neurotransmitter secretion	TAS Traceable Author Statement more info	PubMed
involved_in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of vasoconstriction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info
part_of voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: calcium-activated potassium channel subunit beta-4

Names: BK channel beta subunit 4; BK channel subunit beta-4; BKbeta4; MaxiK channel beta-subunit 4; big potassium channel beta subunit 4; calcium-activated potassium channel, subfamily M subunit beta-4; charybdotoxin receptor subunit beta-4; hbeta4; k(VCA)beta-4; large conductance calcium-dependent potassium ion channel beta 4 subunit; maxi K channel subunit beta-4; potassium channel subfamily M regulatory beta subunit 4; potassium large conductance calcium-activated channel, subfamily M, beta member 4; slo-beta-4

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_014505.6 → NP_055320.4 calcium-activated potassium channel subunit beta-4

See identical proteins and their annotated locations for NP_055320.4

Status: REVIEWED

Source sequence(s)

AC025569, BC042446

Consensus CDS

CCDS8997.1

UniProtKB/Swiss-Prot

Q86W47, Q8IVR3, Q9NPA4, Q9P0G5

Related

ENSP00000258111.4, ENST00000258111.5

Conserved Domains (1) summary

pfam03185
Location:8 → 203

CaKB; Calcium-activated potassium channel, beta subunit

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

70366290..70434292

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047428701.1 → XP_047284657.1 calcium-activated potassium channel subunit beta-4 isoform X2
XM_011538188.3 → XP_011536490.1 calcium-activated potassium channel subunit beta-4 isoform X1

Conserved Domains (1) summary

pfam03185
Location:8 → 155

CaKB; Calcium-activated potassium channel, beta subunit

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

70345760..70413761

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054371752.1 → XP_054227727.1 calcium-activated potassium channel subunit beta-4 isoform X2
XM_054371751.1 → XP_054227726.1 calcium-activated potassium channel subunit beta-4 isoform X1