Cacna1A Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
:: infobox .infobox-gene
Symbol: CACNA1A
Full Name: Calcium Voltage-Gated Channel Subunit Alpha1 A
Chromosomal Location: 19p13.2
NCBI Gene ID: 773
OMIM: 601011
Ensembl ID: ENSG00000141837
UniProt: O00555
Proteins: CaV2.1 (P/Q-type calcium channel)
Associated Diseases: Spinocerebellar Ataxia Type 2 (SCA2), Familial Hemiplegic Migraine, Epilepsy, Developmental Ataxia
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CALCNA1 is a gene/protein encoding a key neuronal protein involved in synaptic function, signal transduction, and cellular homeostasis. Dysfunction of CALCNA1 is associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and related disorders.
CACNA1A encodes the alpha-1A subunit of voltage-gated P/Q-type calcium channels (CaV2.1). These channels are critical for neurotransmitter release at presynaptic terminals, particularly in cerebellar Purkinje cells and hippocampal neurons. Mutations cause various neurological disorders including spinocerebellar ataxias, familial hemiplegic migraine, and epilepsy. Calcium channel dysfunction contributes to excitotoxicity in neurodegenerative diseases.
CaV2.1 channels are expressed in:
- Cerebellum (Purkinje cells, granule cells)
- Hippocampus (CA3 pyramidal cells)
- Cerebral cortex (layer 5)
- Thalamus
- Dorsal root ganglia
High expression in cerebellum explains ataxia phenotypes.
- Mori Y, et al. (1991). "Primary structure and functional expression from complementary DNA of the brain calcium channel." Nature. PMID:1842122
- Ophoff RA, et al. (1996). "Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4." Cell. PMID:8617203
- Mintz IM, et al. (1992). "P-type calcium channels in rat central and peripheral neurons." Neuron. PMID:1314507
The study of Cacna1A Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Villar-Martinez MD, Moreno-Ajona D, Goadsby PJ. "Familial hemiplegic migraine." Handbook of clinical neurology (2024). DOI: 10.1016/B978-0-323-90820-7.00007-0 PubMed: 39174245
- Graves TD et al.. "The episodic ataxias." Handbook of clinical neurology (2024). DOI: 10.1016/B978-0-323-90820-7.00012-4 PubMed: 39174244
- Coutelier M et al.. "Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes." JAMA neurology (2018). DOI: 10.1001/jamaneurol.2017.5121 PubMed: 29482223
- Jen JC, Wan J. "Episodic ataxias." Handbook of clinical neurology (2018). DOI: 10.1016/B978-0-444-64189-2.00013-5 PubMed: 29891059
- Pietrobon D. "CaV2.1 channelopathies." Pflugers Archiv : European journal of physiology (2010). DOI: 10.1007/s00424-010-0802-8 PubMed: 20204399
- Hommersom MP et al.. "CACNA1A haploinsufficiency leads to reduced synaptic function and increased intrinsic excitability." Brain : a journal of neurology (2025). DOI: 10.1093/brain/awae330 PubMed: 39460936
- El Ghaleb Y et al.. "CACNA1I gain-of-function mutations differentially affect channel gating and cause neurodevelopmental disorders." Brain : a journal of neurology (2021). DOI: 10.1093/brain/awab101 PubMed: 33704440
- Cunha P et al.. "Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias." American journal of human genetics (2023). DOI: 10.1016/j.ajhg.2023.05.009 PubMed: 37301203