CACNA2D4 Gene: Calcium Voltage-Gated Channel Auxiliary Subunit Alpha2delta 4
Essential regulator of L-type calcium channels in retinal photoreceptors and neuroendocrine cells
Gene Information Card
| Symbol | CACNA2D4 |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Auxiliary Subunit Alpha2delta 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.33 |
| NCBI Gene ID | 93589 ncbi.nlm.nih.gov/gene/93589 |
| Ensembl ID | ENSG00000151062 |
| UniProt ID | Q7Z3S7 |
| OMIM ID | 608171 |
| HGNC ID | 20202 |
| Aliases | CACNA2D4, MGC26594, CACNA2D4_HUMAN |
Description
CACNA2D4 encodes the alpha-2/delta-4 subunit of voltage-gated calcium channels. This auxiliary subunit regulates channel trafficking, membrane expression, and biophysical properties of L-type calcium channels (Cav1.4). It is predominantly expressed in retinal photoreceptors and plays a critical role in synaptic transmission at the photoreceptor ribbon synapse. Mutations in CACNA2D4 cause autosomal recessive cone dystrophy with night blindness (OMIM #610478).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Retinal cone dystrophy with night blindness | Loss-of-function mutations impair calcium channel function in photoreceptor synaptic terminals, disrupting neurotransmitter release | OMIM #610478, ClinVar, multiple case reports |
| CACNA2D4-related retinopathy | Homozygous or compound heterozygous variants lead to progressive cone dysfunction and nyctalopia | ClinVar, literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | 12.5 | High |
| Brain (cerebellum) | 3.2 | Medium |
| Brain (cortex) | 2.1 | Low |
| Testis | 1.8 | Low |
| Heart | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 4.3 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 2.1 | Low expression |
| HEK293 | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2456C>T (p.Pro819Leu) | Missense | Rare | Loss of calcium channel function |
| c.2029C>T (p.Arg677*) | Nonsense | Rare | Premature truncation, loss of function |
| c.1114G>A (p.Gly372Arg) | Missense | Rare | Impaired subunit trafficking |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations result in loss of calcium channel function due to impaired trafficking or reduced channel activity.
Gain of Function (GOF)
Not reported for CACNA2D4.
Dominant Negative (DN)
Not reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Voltage-gated calcium channel signaling (Reactome R-HSA-5576892)
• Photoreceptor synaptic transmission (KEGG hsa04744)
Protein Summary
The CACNA2D4 protein (UniProt Q7Z3S7) is a 1,135-amino acid auxiliary subunit of voltage-gated calcium channels. It contains a signal peptide, a von Willebrand factor type A domain, and a glycosylphosphatidylinositol (GPI) anchor that tethers it to the plasma membrane. The protein undergoes proteolytic cleavage into alpha2 and delta subunits that remain disulfide-linked. It is essential for proper targeting and function of Cav1.4 channels in retinal photoreceptors, where it modulates channel gating and calcium influx required for sustained neurotransmitter release.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNA2D4 Knockout HEK293 Cell Line | EDJ-KQ624 | Human | 93589 | Details Get a Quote |
| CACNA2D4 Knockout HeLa Cell Line | EDJ-KQ57866 | Human | 93589 | Details Get a Quote |
| CACNA2D4 Knockout A-549 Cell Line | EDJ-KQ66362 | Human | 93589 | Details Get a Quote |
| CACNA2D4 Knockout HCT 116 Cell Line | EDJ-KQ74785 | Human | 93589 | Details Get a Quote |
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