CACNB4 Gene

HGNC Family	Membrane-associated guanylate kinases, Ion channels
Name	calcium channel, voltage-dependent, beta 4 subunit
Description	This gene encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. The protein encoded by this locus plays an important role in calcium channel function by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE), juvenile myoclonic epilepsy (JME), and episodic ataxia, type 5. [provided by RefSeq, Aug 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The CACNB4 gene encodes the β4 subunit of voltage‐gated calcium channels (VGCCs), which plays dual roles in the nervous system. At the plasma membrane, β4 subunits associate with the pore‐forming α1 subunits of P/Q‐type (and related) calcium channels, modulating channel trafficking, clustering at presynaptic sites, and biophysical properties that influence calcium entry and neurotransmitter release. In addition, β4 subunits are involved in channel‐independent signaling; they can translocate to the nucleus where they participate in transcriptional regulation by forming complexes with proteins such as PP2A regulatory subunits, thereby influencing gene expression (for example, repressing tyrosine hydroxylase expression) and ultimately altering neuronal excitability (1,2)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mutations in CACNB4 have been implicated in neurological disorders such as juvenile myoclonic epilepsy and ataxia. Functional studies have shown that missense mutations (e.g., R468Q) can enhance calcium current density—likely by altering the stability of α1–β4 interactions—and thereby may shift the balance between excitatory and inhibitory signaling in the brain (2). Other mutations, such as a p.Leu126Pro variant, disrupt the stable incorporation of β4 into channel complexes and abolish its nuclear targeting, suggesting that both its channel-modulatory and nuclear functions are critical for normal neuronal operation (3). Moreover, while one study supported a role for β4’s nuclear functions in epilepsy pathogenesis, follow‐up work with a truncated β4 variant (R482X) indicated that the distal C‐terminus is not essential for nuclear entry, thus questioning whether defective nuclear targeting underlies the disease mechanism (4). Finally, epidemiological data have identified CACNB4 as one of several Mendelian genes linked to juvenile myoclonic epilepsy, underscoring its importance in maintaining proper neuronal calcium homeostasis (5).\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings indicate that CACNB4 functions not only as an auxiliary subunit modulating VGCC activity at synapses but also as a mediator of activity-dependent gene regulation. Disruption of either role through mutation may contribute to altered neuronal excitability and the pathogenesis of epileptic and ataxic disorders."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "b", "children": [{"type": "t", "text": "Citations:"}]}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Abir Tadmouri, Shigeki Kiyonaka, Maud Barbado, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2012.226"}], "href": "https://doi.org/10.1038/emboj.2012.226"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22892567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22892567"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Iori Ohmori, Mamoru Ouchida, Takafumi Miki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A CACNB4 mutation shows that altered Ca(v)2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2008.07.017"}], "href": "https://doi.org/10.1016/j.nbd.2008.07.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18755274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18755274"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Pierre Coste de Bagneaux, Leonie von Elsner, Tatjana Bierhals, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous missense variant in CACNB4 encoding the auxiliary calcium channel beta4 subunit causes a severe neurodevelopmental disorder and impairs channel and non-channel functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1008625"}], "href": "https://doi.org/10.1371/journal.pgen.1008625"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32176688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32176688"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Solmaz Etemad, Marta Campiglio, Gerald J Obermair, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The juvenile myoclonic epilepsy mutant of the calcium channel β(4) subunit displays normal nuclear targeting in nerve and muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Channels (Austin) (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/chan.29322"}], "href": "https://doi.org/10.4161/chan.29322"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24875574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24875574"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Antonio V Delgado-Escueta, Bobby P C Koeleman, Julia N Bailey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The quest for juvenile myoclonic epilepsy genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsy Behav (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yebeh.2012.06.033"}], "href": "https://doi.org/10.1016/j.yebeh.2012.06.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23756480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23756480"}]}]}]}
Synonyms	CAB4, EA5, CACNLB4, EJM4, EJM6, EIG9, EJM
Proteins	CACB4_HUMAN
NCBI Gene ID	785
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CACNB4 has 5,813 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 120 datasets.

Click the + buttons to view associations for CACNB4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CACNB4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CACNB4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CACNB4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CACNB4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CACNB4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CACNB4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CACNB4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CACNB4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CACNB4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CACNB4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CACNB4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CACNB4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CACNB4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CACNB4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CACNB4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CACNB4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CACNB4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CACNB4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CACNB4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CACNB4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CACNB4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CACNB4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CACNB4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CACNB4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CACNB4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CACNB4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CACNB4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CACNB4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CACNB4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CACNB4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CACNB4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CACNB4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CACNB4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CACNB4 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CACNB4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CACNB4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CACNB4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CACNB4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CACNB4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CACNB4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CACNB4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.