Alternative titles; symbols
HGNC Approved Gene Symbol: CACNB1
Cytogenetic location: 17q12 Genomic coordinates (GRCh38): 17:39,173,453-39,197,669 (from NCBI)
Pragnell et al. (1991) isolated a cDNA clone encoding a protein with high homology to the beta subunit of the rabbit skeletal muscle dihydropyridine-sensitive calcium channel from a rat brain cDNA library. This rat brain beta-subunit cDNA hybridized to a 3.4-kb message that was expressed in high levels in the cerebral hemispheres and hippocampus and much lower levels in cerebellum. The open reading frame encodes 597 amino acids with a predicted mass of 65,679 Da which is 82% homologous with the skeletal muscle beta subunit. Pragnell et al. (1991) suggested that the encoded brain beta subunit, which has a primary structure highly similar to its isoform in skeletal muscle, may have a comparable role as an integral regulatory component of a neuronal calcium channel.
Powers et al. (1992) demonstrated that the skeletal muscle and brain isoforms of the beta subunit are encoded by a single gene. The human skeletal muscle beta-1 cDNA encodes a protein of 523 amino acids that is 97% identical to the rabbit skeletal muscle beta subunit. Two different cDNAs were obtained from the human hippocampus library. One encodes a protein of 478 amino acids that is identical to the skeletal muscle beta subunit except for an internal region of 52 amino acids. The other encodes a protein of 596 amino acids, which is identical to the 478-amino acid skeletal muscle beta subunit at amino acids 1-444; however, it had a unique 152-amino acid C terminus. All 3 cDNAs represented transcripts encoded by a single gene.
Pragnell et al. (1991) localized the human dihydropyridine-sensitive calcium channel beta-subunit (CACNB1) gene to chromosome 17 by analysis of somatic cell hybrids.
Iles et al. (1993) mapped the CACNLB1 gene to 17q11.2-q24, approximately 16 cM centromeric to HOX2B (142961). For this purpose, they used a highly polymorphic dinucleotide repeat found close to the gene in linkage analysis. At the same time, they excluded the CACNLB1 gene as the site of the mutation in malignant hyperthermia (see 145600) families that do not show linkage to chromosome 19q13.1 markers.
To determine the role of the beta-1 subunit in channel activity and excitation-contraction coupling, Gregg et al. (1996) used gene targeting to inactivate the beta-1 subunit in mice. Homozygous mutant fetuses had a phenotype very similar to that seen in mice with mutations in either the alpha-1S subunit ('muscular dysgenic') or in the ryanodine receptor-1 (180901), 'skrr.' All 3 mutants lacked excitation-contraction coupling. Beta-1-null mice died at birth from asphyxia. Electrical stimulation of beta-1-muscle failed to induce twitches; however, contractures were induced by caffeine. In isolated beta-1-null myotubes, action potentials were normal but failed to elicit calcium ion transient. Immunohistochemistry of cultured myotubes showed that not only was the beta-1 subunit absent, but the amount of alpha-1S in the membrane was also undetectable. In contrast, the beta-1 subunit was appropriately localized in alpha-1S-null cells. Therefore, Gregg et al. (1996) concluded that the beta-1 subunit may not only play an important role in the transport/insertion of the alpha-1S subunit into the membrane, but may also be vital for the targeting of the muscle dihydropyridine receptor complex to the transverse tubule/sarcoplasmic reticulum junction.
Gregg, R. G., Messing, A., Strube, C., Beurg, M., Moss, R., Behan, M., Sukhareva, M., Haynes, S., Powell, J. A., Coronado, R., Powers, P. A. Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha-1 subunit and eliminates excitation-contraction coupling. Proc. Nat. Acad. Sci. 93: 13961-13966, 1996. [PubMed: 8943043] [Full Text: https://doi.org/10.1073/pnas.93.24.13961]
Iles, D. E., Segers, B., Sengers, R. C. A., Monsieurs, K., Heytens, L., Halsall, P. J., Hopkins, P. M., Ellis, F. R., Hall-Curran, J. L., Stewart, A. D., Wieringa, B. Genetic mapping of the beta-1- and gamma-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility. Hum. Molec. Genet. 2: 863-868, 1993. [PubMed: 8395940] [Full Text: https://doi.org/10.1093/hmg/2.7.863]
Powers, P. A., Liu, S., Hogan, K., Gregg, R. G. Skeletal muscle and brain isoforms of a beta-subunit of human voltage-dependent calcium channels are encoded by a single gene. J. Biol. Chem. 267: 22967-22972, 1992. [PubMed: 1385409]
Pragnell, M., Sakamoto, J., Jay, S. D., Campbell, K. P. Cloning and tissue-specific expression of the brain calcium channel beta-subunit. FEBS Lett. 291: 253-258, 1991. [PubMed: 1657644] [Full Text: https://doi.org/10.1016/0014-5793(91)81296-k]