CACNA2D1 Gene: Calcium Voltage-Gated Channel Auxiliary Subunit Alpha2delta 1
Key regulator of calcium channel function, implicated in neurological disorders, cardiovascular disease, and cancer.
Gene Information Card
| Symbol | CACNA2D1 |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Auxiliary Subunit Alpha2delta 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.11 |
| NCBI Gene ID | 781 ncbi.nlm.nih.gov/gene/781 |
| Ensembl ID | ENSG00000153956 |
| UniProt ID | P54289 |
| OMIM ID | 114204 |
| HGNC ID | 1395 |
| Aliases | CACNA2D, CACNL2A, MHS3, lncRNA-CACNA2D1 |
Description
The CACNA2D1 gene encodes the alpha-2/delta subunit 1 of voltage-gated calcium channels. This auxiliary subunit is essential for channel trafficking, membrane localization, and modulation of channel kinetics. It is widely expressed in excitable tissues including brain, heart, and skeletal muscle. Mutations in CACNA2D1 are associated with neurodevelopmental disorders, epilepsy, cardiac arrhythmias, and malignant hyperthermia susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 50 | Missense mutations impair calcium channel function, leading to neuronal hyperexcitability. | ClinVar, OMIM #617280 |
| Malignant hyperthermia susceptibility 3 | Altered calcium release in skeletal muscle due to defective channel regulation. | OMIM #154276 |
| Brugada syndrome 9 | Loss-of-function variants reduce cardiac sodium/calcium current, predisposing to arrhythmia. | ClinVar, OMIM #616399 |
| Neurodevelopmental disorder with hypotonia and seizures | De novo missense variants disrupt channel trafficking and gating. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.3 | Medium |
| Skeletal Muscle | 6.7 | Medium |
| Lung | 4.2 | Low |
| Liver | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| H9c2 (cardiomyocyte) | 9.8 | Moderate expression |
| HEK293 (embryonic kidney) | 3.4 | Low expression |
| A549 (lung carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.236C>T (p.Pro79Leu) | Missense | Rare | Loss of function; associated with epileptic encephalopathy |
| c.1019G>A (p.Arg340His) | Missense | Rare | Gain of function; linked to Brugada syndrome |
| c.1745C>T (p.Thr582Met) | Missense | Rare | Dominant negative; malignant hyperthermia susceptibility |
| c.2236G>A (p.Gly746Arg) | Missense | Rare | Loss of function; neurodevelopmental disorder |
Mutation functional classification
Loss of Function (LOF)
Missense variants that impair channel trafficking or reduce calcium current, e.g., p.Pro79Leu.
Gain of Function (GOF)
Variants that enhance channel activity, e.g., p.Arg340His, leading to cardiac arrhythmia.
Dominant Negative (DN)
Variants that interfere with wild-type subunit function, e.g., p.Thr582Met in malignant hyperthermia.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Voltage-gated calcium channel pathway (Reactome: R-HSA-5576891)
• Cardiac conduction (Reactome: R-HSA-5576892)
• Neuronal system (Reactome: R-HSA-112316)
Protein Summary
The CACNA2D1 protein (UniProt P54289) is a 1106-amino acid glycoprotein that undergoes proteolytic cleavage into alpha-2 and delta subunits, which remain linked by disulfide bonds. It is essential for the proper trafficking and function of high-voltage-activated calcium channels (Cav1 and Cav2 families). The protein contains a von Willebrand factor type A domain and multiple glycosylation sites. It modulates channel gating, current density, and inactivation kinetics. Mutations in this gene disrupt calcium homeostasis, leading to neurological and cardiac disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNA2D1 Knockout HEK293 Cell Line | EDJ-KQ622 | Human | 781 | Details Get a Quote |
| CACNA2D1 Knockout HeLa Cell Line | EDJ-KQ18044 | Human | 781 | Details Get a Quote |
| CACNA2D1 Knockout A-549 Cell Line | EDJ-KQ19087 | Human | 781 | Details Get a Quote |
| CACNA2D1 Knockout HCT 116 Cell Line | EDJ-KQ69741 | Human | 781 | Details Get a Quote |
