CACNA1A
Calcium Voltage-Gated Channel Subunit Alpha1 A
Gene Information Card
| Symbol | CACNA1A |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Subunit Alpha1 A |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.13 |
| NCBI Gene ID | 773 ncbi.nlm.nih.gov/gene/773 |
| Ensembl ID | ENSG00000141837 |
| UniProt ID | O00555 |
| OMIM ID | 601011 |
| HGNC ID | 1388 |
| Aliases | CACNL1A4, SCA6, MHP, MHP1, APCA, EA2, FHM, HPCA, CAV2.1, CACN3, CACNL1A4, DEE42, EIEE42, MHP1, SCA6, APCA, EA2, FHM, HPCA, CAV2.1, CACN3, CACNL1A4, DEE42, EIEE42 |
Description
The CACNA1A gene encodes the alpha-1A subunit of the voltage-gated P/Q-type calcium channel (CaV2.1). This channel mediates calcium influx into neurons and is critical for neurotransmitter release, neuronal excitability, and synaptic plasticity. Mutations in CACNA1A are associated with several neurological disorders including familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6), and developmental and epileptic encephalopathy 42 (DEE42).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial Hemiplegic Migraine 1 (FHM1) | Gain-of-function mutations increase channel activity, leading to enhanced neurotransmitter release and cortical spreading depression. | ClinVar, OMIM #141500 |
| Episodic Ataxia Type 2 (EA2) | Loss-of-function mutations reduce channel expression or activity, impairing cerebellar Purkinje cell function. | ClinVar, OMIM #108500 |
| Spinocerebellar Ataxia Type 6 (SCA6) | CAG repeat expansions in the coding region cause polyglutamine tract elongation, leading to protein aggregation and neurodegeneration. | OMIM #183086 |
| Developmental and Epileptic Encephalopathy 42 (DEE42) | Missense and truncating mutations disrupt channel function, causing early-onset seizures and developmental delay. | ClinVar, OMIM #617106 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 28.5 | High |
| Cerebral cortex | 12.3 | Medium |
| Hippocampus | 15.1 | Medium |
| Spinal cord | 8.7 | Medium |
| Heart | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.4 | High expression |
| U-87 MG (glioblastoma) | 6.2 | Medium expression |
| HEK293 (embryonic kidney) | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1997C>T (p.Thr666Met) | Missense | Rare | Gain-of-function; associated with FHM1 |
| c.4636C>T (p.Arg1546*) | Nonsense | Rare | Loss-of-function; associated with EA2 |
| CAG repeat expansion (≥20 repeats) | Repeat expansion | Variable | Polyglutamine tract; associated with SCA6 |
| c.4046G>A (p.Arg1349Gln) | Missense | Rare | Loss-of-function; associated with DEE42 |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and some missense mutations reduce channel expression or activity, leading to EA2 and DEE42.
Gain of Function (GOF)
Specific missense mutations (e.g., p.Thr666Met) increase channel open probability or calcium influx, causing FHM1.
Dominant Negative (DN)
Some missense mutations produce subunits that interfere with wild-type channel assembly, contributing to EA2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Voltage-gated calcium channel pathway (Reactome: R-HSA-5576892)
• Neuronal system (Reactome: R-HSA-112316)
• Calcium signaling pathway (KEGG: hsa04020)
Protein Summary
The CACNA1A protein (CaV2.1 alpha-1A subunit) is a pore-forming component of P/Q-type voltage-gated calcium channels. It consists of four homologous domains (I-IV), each with six transmembrane segments. The channel is predominantly expressed in the central nervous system, especially in cerebellum, hippocampus, and cortex. It mediates calcium entry upon membrane depolarization, triggering neurotransmitter release and regulating neuronal excitability. Mutations in this protein disrupt calcium homeostasis and are linked to migraine, ataxia, and epilepsy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNA1A Knockout HEK293 Cell Line | EDJ-KQ149 | Human | 773 | Details Get a Quote |
| CACNA1A Knockout HCT 116 Cell Line | EDJ-KQ19078 | Human | 773 | Details Get a Quote |
| CACNA1A Knockout HeLa Cell Line | EDJ-KQ52768 | Human | 773 | Details Get a Quote |
| CACNA1A Knockout A-549 Cell Line | EDJ-KQ61237 | Human | 773 | Details Get a Quote |
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