CACNA1A Gene

HGNC Family	Ion channels
Name	calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The gene "}, {"type": "b", "children": [{"type": "t", "text": "CACNA1A"}]}, {"type": "t", "text": " encodes the pore‐forming α1 subunit of neuronal P/Q‐type voltage‐gated calcium channels (Ca<sup>2+</sup> channels, CaV2.1) that are essential for triggering neurotransmitter release at synaptic terminals. Functional studies in both patients and animal models have demonstrated that mutations in CACNA1A underlie a spectrum of neurological disorders, including familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). In FHM1, missense mutations such as R192Q and S218L shift the voltage dependence of channel activation to more negative potentials and increase calcium influx, which is thought to lower the threshold for cortical spreading depression—a process that can precipitate migraine aura—and contribute to cerebellar dysfunction and seizure susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In contrast, the polyglutamine expansions that cause SCA6 seem to promote neurodegeneration not by altering the channel’s intrinsic electrophysiological properties but rather through toxic protein aggregation. Moreover, the proper synaptic localization of CaV2.1 channels is critical for efficient neurotransmission; interactions with presynaptic scaffolding proteins such as Bassoon help cluster these channels at active zones, thereby ensuring tight coupling between calcium entry and transmitter release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings underscore the central role of CACNA1A in regulating neuronal excitability and synaptic communication, with distinct gain‐of‐function or, in some instances, loss‐of‐function mutations leading to varied clinical phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Arn M J M van den Maagdenberg, Daniela Pietrobon, Tommaso Pizzorusso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(04)00085-6"}], "href": "https://doi.org/10.1016/s0896-6273(04"}, {"type": "t", "text": "00085-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15003170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15003170"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Angelita Tottene, Tommaso Fellin, Stefano Pagnutti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Familial hemiplegic migraine mutations increase Ca(2+) influx through single human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.192242399"}], "href": "https://doi.org/10.1073/pnas.192242399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12235360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12235360"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Arn M J M van den Maagdenberg, Tommaso Pizzorusso, Simon Kaja, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High cortical spreading depression susceptibility and migraine-associated symptoms in Ca(v)2.1 S218L mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.21815"}], "href": "https://doi.org/10.1002/ana.21815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20186955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20186955"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Angelita Tottene, Francesca Pivotto, Tommaso Fellin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M501110200"}], "href": "https://doi.org/10.1074/jbc.M501110200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15743764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15743764"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daniela Pietrobon "}, {"type": "b", "children": [{"type": "t", "text": "CaV2.1 channelopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pflugers Arch (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00424-010-0802-8"}], "href": "https://doi.org/10.1007/s00424-010-0802-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20204399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20204399"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lena Damaj, Alexis Lupien-Meilleur, Anne Lortie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2015.21"}], "href": "https://doi.org/10.1038/ejhg.2015.21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25735478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25735478"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "G M Terwindt, R A Ophoff, R van Eijk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of the CACNA1A gene containing region on 19p13 in migraine with and without aura."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/wnl.56.8.1028"}], "href": "https://doi.org/10.1212/wnl.56.8.1028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11320173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11320173"}]}]}]}
Synonyms	SCA6, HPCA, CACNL1A4, EA2, EIEE42, CAV2.1, MHP, MHP1, APCA, BI, FHM
Proteins	CAC1A_HUMAN
NCBI Gene ID	773
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CACNA1A has 8,468 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 122 datasets.

Click the + buttons to view associations for CACNA1A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CACNA1A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CACNA1A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CACNA1A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CACNA1A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CACNA1A protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CACNA1A gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CACNA1A gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CACNA1A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CACNA1A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CACNA1A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CACNA1A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CACNA1A gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CACNA1A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CACNA1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CACNA1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CACNA1A gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CACNA1A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CACNA1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CACNA1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CACNA1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CACNA1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CACNA1A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CACNA1A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CACNA1A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CACNA1A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CACNA1A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CACNA1A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CACNA1A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CACNA1A gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CACNA1A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CACNA1A gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CACNA1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CACNA1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CACNA1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CACNA1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CACNA1A protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CACNA1A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CACNA1A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CACNA1A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CACNA1A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CACNA1A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.