CACNA2D3 calcium voltage-gated channel auxiliary subunit alpha2delta 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CACNA2D3provided by HGNC
Official Full Name: calcium voltage-gated channel auxiliary subunit alpha2delta 3provided by HGNC
Primary source: HGNC:HGNC:15460
See related: Ensembl:ENSG00000157445 MIM:606399; AllianceGenome:HGNC:15460
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HSA272268
Summary: 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. [provided by RefSeq, Jul 2008]
Expression: Broad expression in brain (RPKM 3.0), adrenal (RPKM 1.8) and 16 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.1-p14.3

Exon count:: 38

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (54122552..55074557)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (54156427..55108831)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (54156579..55108584)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Remote ischemic preconditioning reduces mitochondrial apoptosis mediated by calpain 1 activation in myocardial ischemia-reperfusion injury through calcium channel subunit Cacna2d3.
Title: Remote ischemic preconditioning reduces mitochondrial apoptosis mediated by calpain 1 activation in myocardial ischemia-reperfusion injury through calcium channel subunit Cacna2d3.
A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma.
Title: A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma.
CNS sensitisation was associated with a common genetic variant near the calcium channel gene CACNA2D3 at genome-wide significance.
Title: Genes, biomarkers, and clinical features associated with the course of bipolar disorder.
The authors show that ventricular alpha2delta3 expression is low in healthy mice and humans, but significantly elevated in ventricular muscles from DM1 patients with conduction defects.
Title: Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1.
Nine of the 32 (28.1%) iCCA patients had gene mutations at chromosome 3p, totaling 11 mutations across five genes. Those included five (15.6%) BAP1 mutations, two each (6.3%) of CACNA2D3 and RASSF1 mutations, and one each (3.1%) of ATG7 and PLCD1 mutations. Six (18.8%) cases had concurrent loss of chromosome 3p and gene mutations.
Title: Mutations of candidate tumor suppressor genes at chromosome 3p in intrahepatic cholangiocarcinoma.
Findings demonstrate the tumor suppressive role of CACNA2D3 in gliomas. CACNA2D3 operates via Ca 2thorn signaling and the activation of non-canonical Wnt signaling to inhibit cell proliferation and motility and induce apoptosis.
Title: CACNA2D3 is downregulated in gliomas and functions as a tumor suppressor.
The risk of developing anaemia is increased in reproductive age women carriers of A allele of rs1868505 (CACNA2D3) and/or T allele of rs13194491 (HIST1H2BJ).
Title: Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit.
CACNA2D3-mediated increase in intracellular calcium (Ca2+) can induce mitochondrial-mediated apoptosis.
Title: Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma.
CACNA2D3 is a novel tumor suppressor gene responsible for the 3p21 deletion event that plays a critical suppressing role in the development and progression of esophageal squamous cell carcinoma.
Title: Investigation of tumor suppressing function of CACNA2D3 in esophageal squamous cell carcinoma.
CACNA2D3 polymorphism rs1375515 plays important role in iron status and is associated with the levels of iron-related biomarkers, as well as with iron clinical phenotypes (normal, iron de fi cient and anaemic).
Title: Identification of a novel quantitative trait nucleotype related to iron status in a calcium channel gene.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of coronary artery calcification among African Americans, a meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus? EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of antibody response to smallpox vaccine. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of endometrial cancer in E2C2. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3S4145 (e-PCR)
- UniSTS:69892

RH65515 (e-PCR)
- UniSTS:42500

D3S4050 (e-PCR)
- UniSTS:34568

SHGC-146684 (e-PCR)
- UniSTS:175371

D3S1241 (e-PCR)
- UniSTS:147224

SHGC-147153 (e-PCR)
- UniSTS:175643

SHGC-80609 (e-PCR)
- UniSTS:102180

A009K48 (e-PCR)
- UniSTS:81967

SHGC-105280 (e-PCR)
- UniSTS:169264

D3S3660 (e-PCR), detects polymorphism
- UniSTS:48177

D3S1582 (e-PCR)
- UniSTS:54327

AFMA048XB9 (e-PCR)
- UniSTS:53566

RH122935 (e-PCR)
- UniSTS:135232

D3S1236 (e-PCR), detects polymorphism
- UniSTS:19270

SHGC-111457 (e-PCR)
- UniSTS:183626

SHGC-111488 (e-PCR)
- UniSTS:183629

RH26835 (e-PCR)
- UniSTS:84814

D3S3672 (e-PCR), detects polymorphism
- UniSTS:28498

SHGC-150991 (e-PCR)
- UniSTS:173655

D3S2567E (e-PCR)
- UniSTS:148568

D3S1289 (e-PCR), detects polymorphism
- UniSTS:1372

RH122293 (e-PCR)
- UniSTS:137820

WI-21592 (e-PCR)
- UniSTS:80477

RH78885 (e-PCR)
- UniSTS:53085

SHGC-149832 (e-PCR)
- UniSTS:177249

SHGC-77015 (e-PCR)
- UniSTS:3939

SHGC-150992 (e-PCR)
- UniSTS:173667

D3S717 (e-PCR)
- UniSTS:147310

SHGC-106008 (e-PCR)
- UniSTS:169584

STS-AA101173 (e-PCR)
- UniSTS:76941

RH120956 (e-PCR)
- UniSTS:134033

RH104141 (e-PCR)
- UniSTS:98466

G16563 (e-PCR)
- UniSTS:30115

SHGC-155025 (e-PCR)
- UniSTS:183726

D3S1289 (e-PCR), detects polymorphism
- UniSTS:12732

SHGC-155305 (e-PCR)
- UniSTS:183744

D3S1582 (e-PCR)
- UniSTS:26051

D3S1447 (e-PCR)
- UniSTS:148180

RH103162 (e-PCR)
- UniSTS:97496

G32633 (e-PCR)
- UniSTS:117216

D3S3080 (e-PCR)
- UniSTS:27367

SHGC-105801 (e-PCR)
- UniSTS:169448

D3S3666 (e-PCR)
- UniSTS:53745

RH122858 (e-PCR)
- UniSTS:135156

D3S1613 (e-PCR), detects polymorphism
- UniSTS:75252

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables voltage-gated calcium channel activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of presynapse organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in GABA-ergic synapse	IEA Inferred from Electronic Annotation more info
located_in presynaptic active zone membrane	IEA Inferred from Electronic Annotation more info
part_of voltage-gated calcium channel complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: voltage-dependent calcium channel subunit alpha-2/delta-3

Names: alpha2delta-3; calcium channel alpha2-delta3 subunit; calcium channel, voltage-dependent, alpha 2/delta 3 subunit; calcium channel, voltage-dependent, alpha 2/delta subunit 3; voltage-gated calcium channel subunit alpha-2/delta-3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_018398.3 → NP_060868.2 voltage-dependent calcium channel subunit alpha-2/delta-3 precursor

See identical proteins and their annotated locations for NP_060868.2

Status: REVIEWED

Source sequence(s)

AC092057, AC092797, AC104298, AC109584, AC115282, AC133010, AC137673, AC138059

Consensus CDS

CCDS54598.1

UniProtKB/Swiss-Prot

B2RPL6, Q8IZS8, Q9NY16, Q9NY18

Related

ENSP00000419101.1, ENST00000474759.6

Conserved Domains (5) summary

cd01463
Location:242 → 425

vWA_VGCC_like; VWA Voltage gated Calcium channel like: Voltage-gated calcium channels are a complex of five proteins: alpha 1, beta 1, gamma, alpha 2 and delta. The alpha 2 and delta subunits result from proteolytic processing of a single gene product and carries at ...

cd12912
Location:508 → 622

PDC2_MCP_like; second PDC (PhoQ/DcuS/CitA) domain of methyl-accepting chemotaxis proteins and similar domains

pfam08399
Location:113 → 229

VWA_N; VWA N-terminal

pfam08473
Location:655 → 1068

VGCC_alpha2; Neuronal voltage-dependent calcium channel alpha 2acd

pfam02743
Location:442 → 552

dCache_1; Cache domain