CACNA2D3

CACNA2D3
Identifiers
Aliases	CACNA2D3, HSA272268, calcium voltage-gated channel auxiliary subunit alpha2delta 3
External IDs	OMIM: 606399; MGI: 1338890; HomoloGene: 74929; GeneCards: CACNA2D3; OMA:CACNA2D3 - orthologs
Gene location (Human)
Chr.	Chromosome 3 (human)
End	55,074,557 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	29,443,821 bp
RNA expression pattern
	Top expressed in
	middle temporal gyrus; ; Brodmann area 23; ; endothelial cell; ; right auricle; ; apex of heart; ; nucleus accumbens; ; superior frontal gyrus; ; dorsolateral prefrontal cortex; ; gonad; ; prefrontal cortex;
	Top expressed in
	olfactory tubercle; ; neural layer of retina; ; nucleus accumbens; ; medial dorsal nucleus; ; globus pallidus; ; facial motor nucleus; ; subiculum; ; prefrontal cortex; ; superior frontal gyrus; ; anterior horn of spinal cord;
	More reference expression data
	n/a
Gene ontology
Molecular function	metal ion binding; voltage-gated ion channel activity; calcium channel activity; voltage-gated calcium channel activity;
Cellular component	integral component of membrane; plasma membrane; membrane; voltage-gated calcium channel complex;
Biological process	regulation of ion transmembrane transport; ion transport; calcium ion transport; calcium ion transmembrane transport; cardiac conduction;
	Sources:Amigo / QuickGO
Orthologs
	55799
	12294
	ENSG00000157445
	ENSMUSG00000021991
	Q8IZS8
	Q9Z1L5
	NM_018398
	NM_009785
	NP_060868
	NP_033915
	Wikidata
View/Edit Human	View/Edit Mouse

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). ^[5]

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.^[6]

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.^[7] Physical exercise was correlated with a lower methylation frequency of CACNA2D3.^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000157445 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021991 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: Calcium channel, voltage-dependent, alpha 2/delta subunit 3".
^ Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "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. doi:10.1038/bjc.2012.231. PMC 3394973. PMID 22644305.
^ 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 (2008). "Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer". Gastroenterology. 135 (2): 580–90. doi:10.1053/j.gastro.2008.05.041. PMID 18588891.
^ Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, Nakachi K (2009). "DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients". Int. J. Cancer. 124 (11): 2677–82. doi:10.1002/ijc.24231. PMID 19170207.

External links

Human CACNA2D3 genome location and CACNA2D3 gene details page in the UCSC Genome Browser.

Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "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. doi:10.1038/bjc.2012.231. PMC 3394973. PMID 22644305.
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 (2012). "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. doi:10.1245/s10434-011-2202-5. PMID 22395973.
Abo-Dalo B, Kim HG, Roes M, Stefanova M, Higgins A, Shen Y, Mundlos S, Quade BJ, Gusella JF, Kutsche K (2007). "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. doi:10.1002/ajmg.a.32034. PMID 17937436.
Wang KS, Liu XF, Aragam N (2010). "A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder". Schizophrenia Research. 124 (1–3): 192–9. doi:10.1016/j.schres.2010.09.002. PMID 20889312.
Ovsyannikova IG, Kennedy RB, O'Byrne M, Jacobson RM, Pankratz VS, Poland GA (2012). "Genome-wide association study of antibody response to smallpox vaccine". Vaccine. 30 (28): 4182–9. doi:10.1016/j.vaccine.2012.04.055. PMC 3367131. PMID 22542470.
Hanke S, Bugert P, Chudek J, Kovacs G (2001). "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. doi:10.1016/s0378-1119(00)00600-4. PMID 11245980.
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 (2010). "A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene". Cell. 143 (4): 628–38. doi:10.1016/j.cell.2010.09.047. PMC 3040441. PMID 21074052.
Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR (2002). "Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit". Molecular Pharmacology. 62 (3): 485–96. doi:10.1124/mol.62.3.485. PMID 12181424.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000157445 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021991 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: Calcium channel, voltage-dependent, alpha 2/delta subunit 3".

[pmid22644305-6] Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "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. doi:10.1038/bjc.2012.231. PMC 3394973. PMID 22644305.

[pmid18588891-7] 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 (2008). "Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer". Gastroenterology. 135 (2): 580–90. doi:10.1053/j.gastro.2008.05.041. PMID 18588891.

[pmid19170207-8] Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, Nakachi K (2009). "DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients". Int. J. Cancer. 124 (11): 2677–82. doi:10.1002/ijc.24231. PMID 19170207.

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