Gene Symbol: CACNB4
Description: calcium voltage-gated channel auxiliary subunit beta 4
Alias: CAB4, CACNLB4, EA5, EIG9, EJM, EJM4, EJM6, voltage-dependent L-type calcium channel subunit beta-4, calcium channel voltage-dependent subunit beta 4, dihydropyridine-sensitive L-type, calcium channel beta-4 subunit
Species: human
Products:     CACNB4

Top Publications

  1. Machol K, Rousseau J, Ehresmann S, Garcia T, Nguyen T, Spillmann R, et al. Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay. Am J Hum Genet. 2019;104:164-178 pubmed publisher
    ..genes with possible roles in regulation of neuronal development and function, namely H19, SCRG1, RELN, and CACNB4. Our findings suggest a novel SMARCC2-related syndrome that overlaps with neurodevelopmental disorders associated ..
  2. Calder T, de Souza Santos M, Attah V, Klimko J, Fernandez J, Salomon D, et al. Structural and regulatory mutations in Vibrio parahaemolyticus type III secretion systems display variable effects on virulence. FEMS Microbiol Lett. 2014;361:107-14 pubmed publisher
    ..strains exhibited similar levels of swarming motility and T3SS effector production and secretion, but the CAB3 and CAB4 strains, which harbor a mutation in the T3SS2 master regulator gene, formed reduced biofilm growth under T3SS2 ..
  3. Kato T. Testing the sexual imagination hypothesis for gender differences in response to infidelity. BMC Res Notes. 2014;7:860 pubmed publisher
    ..005, a power of .943). Our findings supported the sexual imagination hypothesis but were inconsistent with the EJM hypothesis.
  4. Dhiman S, Galland P. Effects of weak static magnetic fields on the gene expression of seedlings of Arabidopsis thaliana. J Plant Physiol. 2018;231:9-18 pubmed publisher
    ..we generated stimulus-response curves between near zero and 188 μT for the transcript levels of the genes rbcl, cab4, pal4 and ef1...
  5. Xu H, Dorn G, Shetty A, Parihar A, Dave T, Robinson S, et al. A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans. J Pers Med. 2018;8: pubmed publisher
    ..4 × 10-7). We detected association of a variant in a novel intronic locus in the CACNB4 gene meeting genome-wide levels of significance (p = 4.1 × 10-8)...
  6. MacDonald M, Alhassan J, Newman J, Richard M, Gu H, Kelly R, et al. Selective Loss of Smaller Spines in Schizophrenia. Am J Psychiatry. 2017;174:586-594 pubmed publisher
    ..Levels of the tryptic peptide ALFDFLK, found in the schizophrenia risk gene CACNB4, are inversely correlated with the density of smaller, but not larger, spines in schizophrenia subjects...
  7. Cao Y, Li R, Li Y, Zhang T, Wu N, Zhang J, et al. Identification of Transcription Factor-Gene Regulatory Network in Acute Myocardial Infarction. Heart Lung Circ. 2017;26:343-353 pubmed publisher
    ..ETS homologous factor (EHF) was one of transcription factors that had high connectivity with DEGs and regulated CACNB4 in the network...
  8. Dkhil M, Al Shaebi E, Lubbad M, Al Quraishy S. Impact of sex differences in brain response to infection with Plasmodium berghei. Parasitol Res. 2016;115:415-22 pubmed publisher
    ..At the molecular level, P. berghei was able to induce upregulations of Adam23, Cabp1, Cacnb4, Glrb, and Vdac3-mRNA in the brain of mice...
  9. Ghosh Moulick R, Panaitov G, Du L, Mayer D, Offenhäusser A. Neuronal adhesion and growth on nanopatterned EA5-POPC synthetic membranes. Nanoscale. 2018;10:5295-5301 pubmed publisher
    ..Here we have fractionated synthetic membranes using metal nano-grid structures where EphrinA5 (EA5), a neuronal adhesion promoter, was anchored via its Fc domain (immunoglobulin G (IgG)-domain)...

More Information


  1. dela Peña I, Bang M, Lee J, de la Peña J, Kim B, Han D, et al. Common prefrontal cortical gene expression profiles between adolescent SHR/NCrl and WKY/NCrl rats which showed inattention behavior. Behav Brain Res. 2015;291:268-276 pubmed publisher
    ..Creg1, Thrsp, Zeb2), synaptic transmission (e.g. Atp2b2, Syt12, Chrna5), neurological system process (e.g. Atg7, Cacnb4, Grin3a), and immune response (e.g. Atg7, Ip6k2, Mx2)...
  2. Rima M, Daghsni M, Lopez A, Fajloun Z, Lefrancois L, Duñach M, et al. Down-regulation of the Wnt/?-catenin signaling pathway by Cacnb4. Mol Biol Cell. 2017;28:3699-3708 pubmed publisher
    ..Thereby, our results show that ?4-subunit is a TCF4 repressor and therefore appears as an interesting candidate for the regulation of this pathway in neurons where ?4-subunit is specifically expressed. ..
  3. Chung S, Low S, Zembutsu H, Takahashi A, Kubo M, Sasa M, et al. A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients. Breast Cancer Res. 2013;15:R81 pubmed
    ..We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10(-9), OR = 3...
  4. Tadmouri A, Kiyonaka S, Barbado M, Rousset M, Fablet K, Sawamura S, et al. Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy. EMBO J. 2012;31:3730-44 pubmed publisher
    ..Here, we describe a novel signalling pathway in which the VGCC Cacnb4 subunit directly couples neuronal excitability to transcription...
  5. Delgado Escueta A, Koeleman B, Bailey J, Medina M, Duron R. The quest for juvenile myoclonic epilepsy genes. Epilepsy Behav. 2013;28 Suppl 1:S52-7 pubmed publisher
    ..Five Mendelian JME genes have been identified, namely, CACNB4, CASR, GABRa1, GABRD, and Myoclonin1/EFHC1. Three SNP alleles in BRD2, Cx-36, and ME2 and microdeletions in 15q13...
  6. Ohmori I, Ouchida M, Miki T, Mimaki N, Kiyonaka S, Nishiki T, et al. A CACNB4 mutation shows that altered Ca(v)2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy. Neurobiol Dis. 2008;32:349-54 pubmed publisher
    ..All coding exons of SCN1B, GABRG2, and CACNB4 genes were screened for mutations in 38 SCN1A-mutation-positive SMEI probands...
  7. Vendel A, Terry M, Striegel A, Iverson N, Leuranguer V, Rithner C, et al. Alternative splicing of the voltage-gated Ca2+ channel beta4 subunit creates a uniquely folded N-terminal protein binding domain with cell-specific expression in the cerebellar cortex. J Neurosci. 2006;26:2635-44 pubmed
    ..These results have strong bearing on our current understanding of the structure of alternatively spliced Ca2+ channel beta subunits and the cell-specific roles they play in the CNS. ..
  8. Walker D, Bichet D, Campbell K, De Waard M. A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit. J Biol Chem. 1998;273:2361-7 pubmed
    ..This is the first demonstration of a molecular basis for the specificity of functional effects seen for different combinations of these two channel components. ..
  9. Taviaux S, Williams M, Harpold M, Nargeot J, Lory P. Assignment of human genes for beta 2 and beta 4 subunits of voltage-dependent Ca2+ channels to chromosomes 10p12 and 2q22-q23. Hum Genet. 1997;100:151-4 pubmed
    ..CACNB2 (beta 2) and CACNB4 (beta 4), to human chromosomes 10p12 and 2q22-q23, respectively, by fluorescence in situ hybridization...
  10. Betz R, Leibiger B, Farnebo F, Lagercrantz S, Piehl F, Leibiger I, et al. Mapping of the human Ca2+ channel beta 4 subunit to 2q22-23 and its expression in developing mouse. Mamm Genome. 1998;9:310-1 pubmed
  11. Escayg A, Jones J, Kearney J, Hitchcock P, Meisler M. Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic. Genomics. 1998;50:14-22 pubmed human neurological disease, we determined the chromosomal location and intron/exon structure of the human CACNB4 gene...
  12. Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch T, et al. A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation. J Biol Chem. 1999;274:12383-90 pubmed
    ..Our data contribute to our understanding of the molecular organization of calcium channels, providing a functional basis for variation in subunit composition of native P/Q-type channels. ..
  13. Finlin B, Crump S, Satin J, Andres D. Regulation of voltage-gated calcium channel activity by the Rem and Rad GTPases. Proc Natl Acad Sci U S A. 2003;100:14469-74 pubmed
    ..Thus, the RGK GTPase family may provide a mechanism for achieving cross talk between Ras-related GTPases and electrical signaling pathways. ..
  14. Helton T, Horne W. Alternative splicing of the beta 4 subunit has alpha1 subunit subtype-specific effects on Ca2+ channel gating. J Neurosci. 2002;22:1573-82 pubmed
    ..Our data are best explained by a model in which distinct modes of activation and inactivation result from beta-subunit splice variant-specific interactions with an alpha1 subunit gating structure. ..
  15. von Brevern M, Ta N, Shankar A, Wiste A, Siegel A, Radtke A, et al. Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4. Headache. 2006;46:1136-41 pubmed
    ..The present study explored the hypothesis that mutations in CACNA1A, ATP1A2, SCN1A, and the calcium channel beta(4) subunit CACNB4 confer susceptibility to MV.
  16. Iwama K, Iwata A, Shiina M, Mitsuhashi S, Miyatake S, Takata A, et al. A novel mutation in SLC1A3 causes episodic ataxia. J Hum Genet. 2018;63:207-211 pubmed publisher
    ..Mutated genes were found in four of these eight subtypes (EA1, EA2, EA5, and EA6)...
  17. Caddick S, Wang C, Fletcher C, Jenkins N, Copeland N, Hosford D. Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami. J Neurophysiol. 1999;81:2066-74 pubmed
    Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami...
  18. Escayg A, De Waard M, Lee D, Bichet D, Wolf P, Mayer T, et al. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000;66:1531-9 pubmed
    ..To determine the role of the calcium-channel beta4-subunit gene CACNB4 on chromosome 2q22-23 in related human disorders, we screened for mutations in small pedigrees with familial ..
  19. Leikauf G, Concel V, Liu P, Bein K, Berndt A, Ganguly K, et al. Haplotype association mapping of acute lung injury in mice implicates activin a receptor, type 1. Am J Respir Crit Care Med. 2011;183:1499-509 pubmed publisher
    ..5-fold. Associations were identified on chromosomes 1, 2, 4, 11, and 12. Seven genes (Acvr1, Cacnb4, Ccdc148, Galnt13, Rfwd2, Rpap2, and Tgfbr3) had single nucleotide polymorphism (SNP) associations within the gene...
  20. Diriong S, Lory P, Williams M, Ellis S, Harpold M, Taviaux S. Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits. Genomics. 1995;30:605-9 pubmed
    ..Although genetic disorders have been linked to loci 9q34 and 19p13, no genetic disease related to Ca2+ signaling defects has yet been linked to these loci. ..
  21. Day N, Volsen S, McCormack A, Craig P, Smith W, Beattie R, et al. The expression of voltage-dependent calcium channel beta subunits in human hippocampus. Brain Res Mol Brain Res. 1998;60:259-69 pubmed
  22. Rima M, Daghsni M, De Waard S, Gaborit N, Fajloun Z, Ronjat M, et al. The ?4 subunit of the voltage-gated calcium channel (Cacnb4) regulates the rate of cell proliferation in Chinese Hamster Ovary cells. Int J Biochem Cell Biol. 2017;89:57-70 pubmed publisher
    ..Mutations of the neuronal Cacnb4 (?4) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual ..
  23. Kobayashi T, Yamada Y, Fukao M, Shiratori K, Tsutsuura M, Tanimoto K, et al. The GK domain of the voltage-dependent calcium channel beta subunit is essential for binding to the alpha subunit. Biochem Biophys Res Commun. 2007;360:679-83 pubmed
    ..Collectively, our results suggest that the GK domain of the beta subunit is essential for the expression of the functional calcium channel. ..
  24. Vendel A, Rithner C, Lyons B, Horne W. Solution structure of the N-terminal A domain of the human voltage-gated Ca2+channel beta4a subunit. Protein Sci. 2006;15:378-83 pubmed
    ..We have solved the solution structure of the A domain of the human beta4a subunit, a splice variant that we have shown previously to have alpha1 subunit subtype-specific effects on Ca2+ channel trafficking and gating. ..
  25. Volsen S, Day N, McCormack A, Smith W, Craig P, Beattie R, et al. The expression of voltage-dependent calcium channel beta subunits in human cerebellum. Neuroscience. 1997;80:161-74 pubmed
    ..Our cumulative data are consistent with the emerging view that different native alpha1/beta subunit associations occur in the CNS. ..
  26. Burgess D, Jones J, Meisler M, Noebels J. Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell. 1997;88:385-92 pubmed
    ..The lethargic phenotype is the first example of a mammalian neurological disease caused by an inherited defect in a non-pore-forming subunit of a voltage-gated ion channel. ..
  27. Chen Y, Li M, Zhang Y, He L, Yamada Y, Fitzmaurice A, et al. Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels. Nature. 2004;429:675-80 pubmed
    ..The presence of multiple protein-interacting modules in the beta-subunit opens a new dimension to its function as a multi-functional protein. ..
  28. Mubaraki M, Hafiz T, Al Quraishy S, Dkhil M. Oxidative stress and genes regulation of cerebral malaria upon Zizyphus spina-christi treatment in a murine model. Microb Pathog. 2017;107:69-74 pubmed publisher
    ..The mRNA expression of several genes in the brain of mice including Cacnb4, Adam23, Glrb, Vdac3, and Cabp1 was significantly upregulated during P. berghei infection...
  29. Etemad S, Campiglio M, Obermair G, Flucher B. The juvenile myoclonic epilepsy mutant of the calcium channel ?(4) subunit displays normal nuclear targeting in nerve and muscle cells. Channels (Austin). 2014;8:334-43 pubmed
    ..Mutations of the calcium channel ?(4) subunit gene (CACNB4) cause juvenile myoclonic epilepsy in humans and ataxia and epileptic seizures in mice...
  30. Xu X, Lee Y, Holm J, Terry M, Oswald R, Horne W. The Ca2+ channel beta4c subunit interacts with heterochromatin protein 1 via a PXVXL binding motif. J Biol Chem. 2011;286:9677-87 pubmed publisher
    ..An NMR-based two-site docking model of ?4c in complex with dimerized CSD is presented. Possible roles for the interaction are discussed. ..
  31. Kiyonaka S, Uriu Y, Miki T, Mori Y. [Physiological role of presynaptic Ca2+ channel complexes on neurotransmitter release]. Seikagaku. 2008;80:658-61 pubmed
  32. Choi K, Kim J, Kim H, Jung I, Jeong S, Lee S, et al. Genetic Variants Associated with Episodic Ataxia in Korea. Sci Rep. 2017;7:13855 pubmed publisher
    ..Five genes (KCNA1, CACNA1A, CACNB4, SLC1A3, and UBR4) have been linked to EA...
  33. Graves T, Hanna M. Episodic ataxia: SLC1A3 and CACNB4 do not explain the apparent genetic heterogeneity. J Neurol. 2008;255:1097-9 pubmed publisher
  34. Lory P, Ophoff R, Nahmias J. Towards a unified nomenclature describing voltage-gated calcium channel genes. Hum Genet. 1997;100:149-50 pubmed
    ..A unified nomenclature for describing voltage-gated calcium channel genes is proposed. The terminology has been approved by the HUGO/GDB nomenclature committee. ..