CACNB4: Calcium Voltage-Gated Channel Auxiliary Subunit Beta 4
A key regulator of calcium channel function implicated in epilepsy, ataxia, and migraine
Gene Information Card
| Symbol | CACNB4 |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Auxiliary Subunit Beta 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q23.3 |
| NCBI Gene ID | 785 ncbi.nlm.nih.gov/gene/785 |
| Ensembl ID | ENSG00000182389 |
| UniProt ID | Q9UBN6 |
| OMIM ID | 601949 |
| HGNC ID | 1404 |
| Aliases | CAB4, CACNLB4, EA5, EIG9, EJM4, EJM5, MGC41860 |
Description
CACNB4 encodes the beta-4 subunit of voltage-gated calcium channels. This auxiliary subunit modulates channel gating, trafficking, and current kinetics. It is highly expressed in the brain and plays a critical role in neuronal excitability. Mutations in CACNB4 are associated with several neurological disorders including juvenile myoclonic epilepsy, episodic ataxia type 5, and familial hemiplegic migraine.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Episodic ataxia type 5 (EA5) | Missense mutations (e.g., R482C) impair calcium channel inactivation, leading to altered Purkinje cell firing | OMIM #613855; ClinVar |
| Juvenile myoclonic epilepsy (EJM4/EJM5) | Loss-of-function variants reduce calcium current density, increasing neuronal hyperexcitability | OMIM #611942; NCBI |
| Familial hemiplegic migraine | Gain-of-function mutations enhance channel activity, predisposing to cortical spreading depression | OMIM #141500; ClinVar |
| Generalized epilepsy with febrile seizures plus (GEFS+) | Rare missense variants alter channel beta subunit interaction, disrupting neuronal calcium homeostasis | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 28.5 | High |
| Brain (cerebral cortex) | 22.1 | High |
| Heart | 6.3 | Medium |
| Skeletal muscle | 4.8 | Medium |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.7 | Neuronal model |
| U-87 MG (glioblastoma) | 12.4 | Glial model |
| HEK293 (embryonic kidney) | 3.1 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1444C>T (p.Arg482Cys) | Missense | Rare | Impaired inactivation; associated with EA5 |
| c.1048G>A (p.Glu350Lys) | Missense | Rare | Reduced current density; linked to JME |
| c.1190T>C (p.Leu397Pro) | Missense | Rare | Altered beta subunit interaction; GEFS+ |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; severe epilepsy |
Mutation functional classification
Loss of Function (LOF)
p.Glu350Lys reduces calcium current density, leading to neuronal hyperexcitability and epilepsy.
Gain of Function (GOF)
p.Arg482Cys impairs inactivation, causing persistent calcium influx and ataxia.
Dominant Negative (DN)
p.Leu397Pro disrupts normal beta subunit assembly, reducing functional channel number.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Voltage-gated calcium channel pathway (Reactome: R-HSA-5576892)
• Neuronal system (KEGG: hsa04728)
• Calcium signaling pathway (KEGG: hsa04020)
Protein Summary
The CACNB4 protein (beta-4 subunit) is a cytosolic auxiliary subunit of high-voltage-activated calcium channels. It contains a conserved SH3 domain and a guanylate kinase-like domain that mediate binding to the alpha-1 pore-forming subunit. Beta-4 modulates channel activation/inactivation kinetics, enhances membrane trafficking, and regulates calcium-dependent processes such as neurotransmitter release and gene expression. In the brain, it is particularly abundant in cerebellar Purkinje cells and cortical neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNB4 Knockout HEK293 Cell Line | EDJ-KQ627 | Human | 785 | Details Get a Quote |
| CACNB4 Knockout HCT 116 Cell Line | EDJ-KQ19095 | Human | 785 | Details Get a Quote |
| CACNB4 Knockout HeLa Cell Line | EDJ-KQ19096 | Human | 785 | Details Get a Quote |
| CACNB4 Knockout A-549 Cell Line | EDJ-KQ61243 | Human | 785 | Details Get a Quote |
