CACNA1D
Calcium Voltage-Gated Channel Subunit Alpha1 D
Gene Information Card
| Symbol | CACNA1D |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Subunit Alpha1 D |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.1 |
| NCBI Gene ID | 776 ncbi.nlm.nih.gov/gene/776 |
| Ensembl ID | ENSG00000157388 |
| UniProt ID | Q01668 |
| OMIM ID | 114206 |
| HGNC ID | 1392 |
| Aliases | Cav1.3, CCHL1A2, CACN4, CACNL1A2, SANDD |
Description
CACNA1D encodes the alpha-1D subunit of a voltage-dependent L-type calcium channel (Cav1.3). This channel mediates calcium influx in response to membrane depolarization, playing critical roles in cardiac pacemaking, neuronal firing, hormone secretion, and auditory transduction. Mutations in CACNA1D are associated with sinoatrial node dysfunction and deafness (SANDD syndrome), primary aldosteronism, and neuropsychiatric disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sinoatrial node dysfunction and deafness (SANDD) | Loss-of-function mutations impair cardiac pacemaker calcium current, leading to bradycardia and sensorineural hearing loss | ClinVar, OMIM #614896 |
| Primary aldosteronism (PASNA) | Gain-of-function mutations increase aldosterone production in adrenal glomerulosa cells, causing hypertension | OMIM #617027, ClinVar |
| Autism spectrum disorder | De novo missense variants alter channel gating, affecting neuronal excitability and synaptic plasticity | ClinVar, PubMed studies |
| Epilepsy | Rare gain-of-function variants contribute to neuronal hyperexcitability | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 11.2 | Medium |
| Heart | 8.5 | Medium |
| Adrenal gland | 6.3 | Low |
| Cochlea | 5.1 | Low |
| Pancreas | 4.8 | Low |
| Skeletal muscle | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 9.7 | Neuronal model |
| HEK293 | 2.3 | Low endogenous expression |
| H295R (adrenocortical) | 7.1 | Adrenal model |
| iPS-derived cardiomyocytes | 10.5 | Cardiac model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly403Arg | Missense | <0.01% | Gain-of-function; associated with PASNA |
| p.Ala749Gly | Missense | <0.01% | Loss-of-function; associated with SANDD |
| p.Arg990His | Missense | <0.01% | Gain-of-function; linked to autism |
| p.Gly407Arg | Missense | <0.01% | Gain-of-function; primary aldosteronism |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce calcium current (e.g., p.Ala749Gly) lead to bradycardia and deafness (SANDD).
Gain of Function (GOF)
Mutations that increase channel activity (e.g., p.Gly403Arg) cause aldosterone excess and hypertension (PASNA).
Dominant Negative (DN)
Not well documented for CACNA1D; most reported mutations are heterozygous with dominant effects via altered gating.
View complete mutation data：
Gene Ontology (GO)
Pathways
• WP:WP536 – Calcium regulation in cardiac cells
• WP:WP203 – Voltage-gated calcium channels
• Reactome:R-HSA-5576892 – Cardiac conduction
• Reactome:R-HSA-112314 – Neurotransmitter release cycle
Protein Summary
The CACNA1D protein (Cav1.3) is a pore-forming alpha-1 subunit of L-type voltage-gated calcium channels. It consists of four homologous domains (I-IV) each with six transmembrane segments. The channel is activated by membrane depolarization and mediates calcium entry, which triggers cardiac pacemaker depolarization, neurotransmitter release, hormone secretion, and gene expression. Cav1.3 is highly expressed in sinoatrial node, brain, adrenal cortex, and cochlear hair cells. Its dysfunction underlies cardiac arrhythmias, deafness, endocrine disorders, and neurodevelopmental conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNA1D Knockout Caco-2 Cell Line | EDJ-KQ12 | Human | 776 | Details Get a Quote |
| CACNA1D Knockout HEK293 Cell Line | EDJ-KQ616 | Human | 776 | Details Get a Quote |
| CACNA1D Knockout A-549 Cell Line | EDJ-KQ19080 | Human | 776 | Details Get a Quote |
| CACNA1D Knockout HeLa Cell Line | EDJ-KQ52771 | Human | 776 | Details Get a Quote |
| CACNA1D Knockout HCT 116 Cell Line | EDJ-KQ69737 | Human | 776 | Details Get a Quote |
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