CACNA2D3 explained

Calcium channel, voltage-dependent, alpha 2/delta subunit 3 is a protein that in humans is encoded by the CACNA2D3 gene on chromosome 3 (locus 3p21.1).^[1]

Function

This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. 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. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.

Clinical significance

Number of studies reported an association between methylation of the CACNA2D3 gene and cancer.

Breast cancer

Methylation-dependent transcriptional silencing of CACNA2D3 gene may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease.^[2]

Gastric cancer

The loss of CACNA2D3 gene expression through aberrant promoter hypermethylation may contribute to gastric carcinogenesis, and CACNA2D3 gene methylation is a useful prognostic marker for patients with advanced gastric cancer.^[3] Physical exercise was correlated with a lower methylation frequency of CACNA2D3.^[4]

Further reading

• Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T . Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas . British Journal of Cancer . 107 . 2 . 375–81 . 2012 . 22644305 . 3394973 . 10.1038/bjc.2012.231 .
• Leone PE, González MB, Elosua C, Gómez-Moreta JA, Lumbreras E, Robledo C, Santos-Briz A, Valero JM, de la Guardia RD, Gutiérrez NC, Hernández JM, García JL . Integration of global spectral karyotyping, CGH arrays, and expression arrays reveals important genes in the pathogenesis of glioblastoma multiforme . Annals of Surgical Oncology . 19 . 7 . 2367–79 . 2012 . 22395973 . 10.1245/s10434-011-2202-5 . 1687472 .
• Abo-Dalo B, Kim HG, Roes M, Stefanova M, Higgins A, Shen Y, Mundlos S, Quade BJ, Gusella JF, Kutsche K . Extensive molecular genetic analysis of the 3p14.3 region in patients with Zimmermann-Laband syndrome . American Journal of Medical Genetics Part A . 143A . 22 . 2668–74 . 2007 . 17937436 . 10.1002/ajmg.a.32034 . 22798244 .
• Wang KS, Liu XF, Aragam N . A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder . Schizophrenia Research . 124 . 1–3 . 192–9 . 2010 . 20889312 . 10.1016/j.schres.2010.09.002 . 21402201 .
• Ovsyannikova IG, Kennedy RB, O'Byrne M, Jacobson RM, Pankratz VS, Poland GA . Genome-wide association study of antibody response to smallpox vaccine . Vaccine . 30 . 28 . 4182–9 . 2012 . 22542470 . 3367131 . 10.1016/j.vaccine.2012.04.055 .
• Hanke S, Bugert P, Chudek J, Kovacs G . Cloning a calcium channel alpha2delta-3 subunit gene from a putative tumor suppressor gene region at chromosome 3p21.1 in conventional renal cell carcinoma . Gene . 264 . 1 . 69–75 . 2001 . 11245980 . 10.1016/s0378-1119(00)00600-4.
• Neely GG, Hess A, Costigan M, Keene AC, Goulas S, Langeslag M, Griffin RS, Belfer I, Dai F, Smith SB, Diatchenko L, Gupta V, Xia CP, Amann S, Kreitz S, Heindl-Erdmann C, Wolz S, Ly CV, Arora S, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Gibson DG, Truong D, Schramek D, Zoranovic T, Cronin SJ, Angjeli B, Brune K, Dietzl G, Maixner W, Meixner A, Thomas W, Pospisilik JA, Alenius M, Kress M, Subramaniam S, Garrity PA, Bellen HJ, Woolf CJ, Penninger JM . A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene . Cell . 143 . 4 . 628–38 . 2010 . 21074052 . 3040441 . 10.1016/j.cell.2010.09.047 .
• Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR . Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit . Molecular Pharmacology . 62 . 3 . 485–96 . 2002 . 12181424 . 10.1124/mol.62.3.485 .

Notes and References

1. Web site: Entrez Gene: Calcium channel, voltage-dependent, alpha 2/delta subunit 3 .
2. Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T . Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas . Br. J. Cancer . 107 . 2 . 375–81 . 2012 . 22644305 . 3394973 . 10.1038/bjc.2012.231 .
3. Wanajo A, Sasaki A, Nagasaki H, Shimada S, Otsubo T, Owaki S, Shimizu Y, Eishi Y, Kojima K, Nakajima Y, Kawano T, Yuasa Y, Akiyama Y . Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer . Gastroenterology . 135 . 2 . 580–90 . 2008 . 18588891 . 10.1053/j.gastro.2008.05.041 . free .
4. Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, Nakachi K . DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients . Int. J. Cancer . 124 . 11 . 2677–82 . 2009 . 19170207 . 10.1002/ijc.24231 . 46627170 . free .