CACNA1A calcium voltage-gated channel subunit alpha1 A [Homo sapiens (human)] - Gene

Summary

Official Symbol: CACNA1Aprovided by HGNC
Official Full Name: calcium voltage-gated channel subunit alpha1 Aprovided by HGNC
Primary source: HGNC:HGNC:1388
See related: Ensembl:ENSG00000141837 MIM:601011; AllianceGenome:HGNC:1388
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: BI; EA2; FHM; MHP; APCA; HPCA; MHP1; SCA6; DEE42; CAV2.1; EIEE42; CACNL1A4
Summary: Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]
Expression: Biased expression in brain (RPKM 5.1), stomach (RPKM 1.8) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.13

Exon count:: 49

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (13206442..13506479, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (13331719..13631840, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (13317256..13617293, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

Natural history of non-polyglutamine CACNA1A disease in Austria.
Title: Natural history of non-polyglutamine CACNA1A disease in Austria.
Adult-onset Migraine and Very Late Onset Ataxia Due to a Novel Pathogenic Variant of the CACNA1A Gene.
Title: Adult-onset Migraine and Very Late Onset Ataxia Due to a Novel Pathogenic Variant of the CACNA1A Gene.
CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options.
Title: CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options.
High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.
Title: High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.
Clinical and genetic characterization of CACNA1A-related disease.
Title: Clinical and genetic characterization of CACNA1A-related disease.
The complexities of CACNA1A in clinical neurogenetics.
Title: The complexities of CACNA1A in clinical neurogenetics.
Next-generation sequencing identified a novel CACNA1A I1379F variant in a familial hemiplegic migraine type 1 pedigree: A case report.
Title: Next-generation sequencing identified a novel CACNA1A I1379F variant in a familial hemiplegic migraine type 1 pedigree: A case report.
Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2.
Title: Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2.
Three Novel Genetic Variants in the FAM110D, CACNA1A, and NLRP12 Genes Are Associated With Susceptibility to Hypertension Among Dai People.
Title: Three Novel Genetic Variants in the FAM110D, CACNA1A, and NLRP12 Genes Are Associated With Susceptibility to Hypertension Among Dai People.
Advances in genotype-phenotype associations for CACNA1A-related epilepsies.
Title: Advances in genotype-phenotype associations for CACNA1A-related epilepsies.

Submit: New GeneRIF Correction See all GeneRIFs (206)

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

Associated conditions

Description	Tests
Developmental and epileptic encephalopathy, 42 MedGen: C4310716 OMIM: 617106 GeneReviews: Not available	Compare labs
Episodic ataxia type 2 MedGen: C1720416 OMIM: 108500 GeneReviews: Hereditary Ataxia Overview	Compare labs
Migraine, familial hemiplegic, 1 MedGen: C1832884 OMIM: 141500 GeneReviews: Familial Hemiplegic Migraine	Compare labs
Spinocerebellar ataxia type 6 MedGen: C0752124 OMIM: 183086 GeneReviews: Hereditary Ataxia Overview, Spinocerebellar Ataxia Type 6	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2017-05-21) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2017-05-21) ClinGen Genome Curation PagePubMed

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH48188 (e-PCR)
- UniSTS:8267

D19S564 (e-PCR)
- UniSTS:25194

SHGC-83991 (e-PCR)
- UniSTS:104622

G54374 (e-PCR)
- UniSTS:116147

G54375 (e-PCR)
- UniSTS:116148

G54376 (e-PCR)
- UniSTS:116149

G54377 (e-PCR)
- UniSTS:116150

G54378 (e-PCR)
- UniSTS:116151

G54379 (e-PCR)
- UniSTS:116152

G54380 (e-PCR)
- UniSTS:116153

G54381 (e-PCR)
- UniSTS:116154

G54382 (e-PCR)
- UniSTS:116155

G54383 (e-PCR)
- UniSTS:116156

G54384 (e-PCR)
- UniSTS:116157

G54385 (e-PCR)
- UniSTS:116158

G54386 (e-PCR)
- UniSTS:116159

G54387 (e-PCR)
- UniSTS:116160

G54388 (e-PCR)
- UniSTS:116161

G54389 (e-PCR)
- UniSTS:116162

G54390 (e-PCR)
- UniSTS:116163

G54391 (e-PCR)
- UniSTS:116164

G54392 (e-PCR)
- UniSTS:116165

G54393 (e-PCR)
- UniSTS:116166

G54394 (e-PCR)
- UniSTS:116167

G54395 (e-PCR)
- UniSTS:116168

G54397 (e-PCR)
- UniSTS:116170

G54398 (e-PCR)
- UniSTS:116171

G54401 (e-PCR)
- UniSTS:116174

G59885 (e-PCR)
- UniSTS:137168

G54403 (e-PCR)
- UniSTS:116176

G54404 (e-PCR)
- UniSTS:116177

G54405 (e-PCR)
- UniSTS:116178

G54406 (e-PCR)
- UniSTS:116179

G54407 (e-PCR)
- UniSTS:116180

G54408 (e-PCR)
- UniSTS:116181

G54409 (e-PCR)
- UniSTS:116182

G54410 (e-PCR)
- UniSTS:116183

G54411 (e-PCR)
- UniSTS:116184

G54412 (e-PCR)
- UniSTS:116185

G54413 (e-PCR)
- UniSTS:116186

G54414 (e-PCR)
- UniSTS:116187

G54415 (e-PCR)
- UniSTS:116188

G54416 (e-PCR)
- UniSTS:116189

G54417 (e-PCR)
- UniSTS:116190

G54418 (e-PCR)
- UniSTS:116191

G54419 (e-PCR)
- UniSTS:116192

G54420 (e-PCR)
- UniSTS:116193

G54422 (e-PCR)
- UniSTS:116195

G54423 (e-PCR)
- UniSTS:116196

G54424 (e-PCR)
- UniSTS:116197

G49219 (e-PCR)
- UniSTS:140782

G49217 (e-PCR)
- UniSTS:140784

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables amyloid-beta binding	IC Inferred by Curator more info	PubMed
enables high voltage-gated calcium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables high voltage-gated calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables high voltage-gated calcium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables syntaxin binding	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated calcium channel activity	IGI Inferred from Genetic Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in calcium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to amyloid-beta	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to amyloid-beta	IGI Inferred from Genetic Interaction more info	PubMed
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
involved_in response to amyloid-beta	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cell projection	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in neuronal cell body	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	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 P/Q-type calcium channel subunit alpha-1A

Names: brain calcium channel 1; brain calcium channel I; calcium channel, L type, alpha-1 polypeptide; calcium channel, voltage-dependent, P/Q type, alpha 1A subunit; fetal brain Ca2+ voltage-gated channel alpha1A pore-forming subunit; voltage-gated calcium channel subunit alpha Cav2.1

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.

Genomic

NG_011569.1 RefSeqGene

Range

5001..305019

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_7

mRNA and Protein(s)

NM_000068.4 → NP_000059.3 voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 1

See identical proteins and their annotated locations for NP_000059.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) uses an alternate splice site in the 3' coding region that results in a frameshift, compared to variant 2. The resulting isoform (1) has a shorter and distinct C-terminus that does not include the polyglutamine tract, compared to isoform 2.

Source sequence(s)

AB035726, AC008540, AC011446, AF004883, BQ340521

Consensus CDS

CCDS82301.1

UniProtKB/TrEMBL

A0A384DVW2

Related

ENSP00000490617.1, ENST00000637432.1

Conserved Domains (3) summary

pfam00520
Location:1586 → 1827

Ion_trans; Ion transport protein

pfam08763
Location:1900 → 1974

Ca_chan_IQ; Voltage gated calcium channel IQ domain

pfam16905
Location:1835 → 1898

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_001127221.2 → NP_001120693.1 voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 3

See identical proteins and their annotated locations for NP_001120693.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses two alternate splice sites, lacks two alternate exons, and includes an additional exon, compared to variant 2. The resulting isoform (3) differs at 3 internal regions and has a shorter and distinct C-terminus that does not include the polyglutamine tract, compared to isoform 2.

Source sequence(s)

AC008540, AC011446, AC124224, AF004883, X99897

Consensus CDS

CCDS45999.1

UniProtKB/TrEMBL

A0A1B0GTI4

Related

ENSP00000489913.1, ENST00000638009.2

Conserved Domains (3) summary

pfam00520
Location:1583 → 1822

Ion_trans; Ion transport protein

pfam08763
Location:1895 → 1969

Ca_chan_IQ; Voltage gated calcium channel IQ domain

pfam16905
Location:1830 → 1893

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_001127222.2 → NP_001120694.1 voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses two alternate in-frame splice sites and lacks an alternate in-frame exon, compared to variant 2. The resulting isoform (4) differs at three internal regions, compared to isoform 2, and includes the polyglutamine tract near the C-terminus.

Source sequence(s)

AB035727, AC008540, AC011446, AC022436, AC026805, AC124224, AF004883

Consensus CDS

CCDS45998.1

UniProtKB/Swiss-Prot

J3KP41, O00555, P78510, P78511, Q16290, Q92690, Q99790, Q99791, Q99792, Q99793, Q9NS88, Q9UDC4

UniProtKB/TrEMBL

A0A1B0GU81

Related

ENSP00000353362.5, ENST00000360228.11

Conserved Domains (4) summary

pfam00520
Location:1564 → 1821

Ion_trans; Ion transport protein

pfam08763
Location:1894 → 1968

Ca_chan_IQ; Voltage gated calcium channel IQ domain

pfam16905
Location:1822 → 1892

GPHH; Voltage-dependent L-type calcium channel, IQ-associated

cl28033
Location:2233 → 2503

Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region
NM_001174080.2 → NP_001167551.1 voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 5

See identical proteins and their annotated locations for NP_001167551.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses two alternate splice sites, compared to variant 2. The resulting isoform (5) lacks an internal 3-aa segment and has a shorter and distinct C-terminus that does not include the polyglutamine tract, compared to isoform 2.

Source sequence(s)

AC008540, AC011446, AF004883, FJ040507

Consensus CDS

CCDS82302.1

UniProtKB/TrEMBL

A0A384DVW2, B5TYJ1

Related

ENSP00000490578.1, ENST00000636549.1

Conserved Domains (3) summary

pfam00520
Location:1583 → 1824

Ion_trans; Ion transport protein

pfam08763
Location:1897 → 1971

Ca_chan_IQ; Voltage gated calcium channel IQ domain

pfam16905
Location:1832 → 1895

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_023035.3 → NP_075461.2 voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform 2

See identical proteins and their annotated locations for NP_075461.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2). This variant includes a (CAG)n-repeat in the coding region, resulting in a polyglutamine tract near the C-terminus.

Source sequence(s)

AB035726, AC008540, AC011446, AF004884, BQ340521

Consensus CDS

CCDS82300.1

UniProtKB/TrEMBL

A0A087WW63, A0A1B0GU81

Related

ENSP00000489829.1, ENST00000638029.1

Conserved Domains (4) summary

pfam00520
Location:1586 → 1827

Ion_trans; Ion transport protein

pfam05550
Location:2352 → 2424

Peptidase_C53; Pestivirus Npro endopeptidase C53

pfam08763
Location:1900 → 1974

Ca_chan_IQ; Voltage gated calcium channel IQ domain

pfam16905
Location:1835 → 1898

GPHH; Voltage-dependent L-type calcium channel, IQ-associated