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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KCNMB4
potassium calcium-activated channel subfamily M regulatory beta subunit 4
Chromosome 12 · 12q15
NCBI Gene: 27345Ensembl: ENSG00000135643.5HGNC: HGNC:6289UniProt: Q86W47
30PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
neuronal action potentialprotein bindingplasma membranevoltage-gated potassium channel complexsmoking initiationinsomniaovarian neoplasmtrauma complication
✦AI Summary

KCNMB4 encodes the beta-4 regulatory subunit of large-conductance calcium-activated potassium (BK/KCa1.1) channels, which modulates channel gating kinetics and calcium sensitivity. As a regulatory component, KCNMB4 decreases calcium sensitivity and gating kinetics while providing fast deactivation kinetics, and confers resistance to charybdotoxin [UniProt]. The β4-subunit is highly expressed in ocular tissues, particularly the conventional outflow pathway, where it significantly regulates aqueous humor outflow facility and intraocular pressure 1. KCNMB4 expression has been implicated in multiple pathological contexts. In osteosarcoma, recurrent KCNMB4-CCND3 fusion genes promote tumor cell motility 2. The gene contributes to paclitaxel resistance in nasopharyngeal carcinoma through PRMT5-mediated upregulation via histone methylation 3. KCNMB4 expression is also upregulated in SARS-CoV-2 infected cells, potentially through a competitive endogenous RNA mechanism involving viral circ_3205 and miR-298 4. Additionally, KCNMB4 is involved in neuroblastoma pathogenesis and action potential regulation 5. The clinical significance extends to potential therapeutic targeting for glaucoma treatment through modulation of intraocular pressure and as a biomarker in various cancers where it correlates with chemoresistance and tumor progression.

Sources cited
1
KCNMB4 is highly expressed in conventional outflow pathway and regulates aqueous humor outflow facility
PMID: 32203982
2
KCNMB4-CCND3 fusion genes in osteosarcoma promote tumor cell motility
PMID: 25300797
3
PRMT5 upregulates KCNMB4 expression via histone methylation to promote paclitaxel resistance in nasopharyngeal carcinoma
PMID: 41513606
4
KCNMB4 expression is upregulated in SARS-CoV-2 infected cells through ceRNA mechanism
PMID: 35039944
5
KCNMB4 is involved in neuroblastoma pathogenesis and action potential regulation
PMID: 26398570
Disease Associationsⓘ20
smoking initiationOpen Targets
0.39Weak
insomniaOpen Targets
0.31Weak
ovarian neoplasmOpen Targets
0.25Weak
trauma complicationOpen Targets
0.25Weak
inflammatory bowel diseaseOpen Targets
0.24Weak
X-linked non-syndromic intellectual disabilityOpen Targets
0.10Suggestive
corneal degenerationOpen Targets
0.10Suggestive
osteoarthritis, kneeOpen Targets
0.09Suggestive
Generalized epilepsy with febrile seizures-plusOpen Targets
0.09Suggestive
osteoarthritis, hipOpen Targets
0.08Suggestive
generalised epilepsyOpen Targets
0.08Suggestive
Abruptio PlacentaeOpen Targets
0.07Suggestive
15q13.3 microdeletion syndromeOpen Targets
0.07Suggestive
chromosome 15q13.3 microdeletion syndromeOpen Targets
0.07Suggestive
intellectual disability, autosomal dominant 10Open Targets
0.07Suggestive
intellectual disability, autosomal dominant 3Open Targets
0.07Suggestive
juvenile myoclonic epilepsyOpen Targets
0.06Suggestive
hypertensionOpen Targets
0.06Suggestive
genetic developmental and epileptic encephalopathyOpen Targets
0.06Suggestive
generalized epilepsy with febrile seizures plus, type 7Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCNMA1Protein interaction100%KCNU1Protein interaction98%KCNN3Protein interaction98%KCNN4Protein interaction98%KCNN2Protein interaction96%PRKG1Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Heart
26%
Lung
20%
Ovary
14%
Bone Marrow
3%
Liver
3%
Gene Interaction Network
Click a node to explore
KCNMB4KCNMA1KCNU1KCNN3KCNN4KCNN2PRKG1
PROTEIN STRUCTURE
Preparing viewer…
PDB9CZM · 2.57 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.40Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.13 [0.05–0.40]
RankingsWhere KCNMB4 stands among ~20K protein-coding genes
  • #11,951of 20,598
    Most Researched30
  • #2,001of 17,882
    Most Constrained (LOEUF)0.40 · top quartile
Genes detectedKCNMB4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma.
PMID: 25300797
J Hematol Oncol · 2014
1.00
2
Family-Based Cohort Association Study of PRKCB1, CBLN1 and KCNMB4 Gene Polymorphisms and Autism in Polish Population.
PMID: 34562210
J Autism Dev Disord · 2022
0.90
3
PRMT5 upregulates KCNMB4 expression via histone methylation to promote paclitaxel resistance in advanced nasopharyngeal carcinoma.
PMID: 41513606
Cell Death Dis · 2026
0.80
4
Competing endogenous RNA network mediated by circ_3205 in SARS-CoV-2 infected cells.
PMID: 35039944
Cell Mol Life Sci · 2022
0.70
5
Oligodendrocytes, BK channels and the preservation of myelin.
PMID: 34909188
F1000Res · 2021
0.60