CACNG4 Gene: Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 4
A comprehensive guide to CACNG4, its function, associated diseases, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | CACNG4 |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q24.2 |
| NCBI Gene ID | 27092 ncbi.nlm.nih.gov/gene/27092 |
| Ensembl ID | ENSG00000075429 |
| UniProt ID | Q9UBN1 |
| OMIM ID | 606404 |
| HGNC ID | 1406 |
| Aliases | CACNG4; MGC24983; FLJ90586 |
Description
The CACNG4 gene encodes the gamma-4 subunit of voltage-gated calcium channels (VGCCs). This auxiliary subunit modulates channel activity, affecting calcium influx and neuronal excitability. CACNG4 is predominantly expressed in the brain and is involved in synaptic transmission and plasticity. Mutations and altered expression have been linked to neurological disorders, including epilepsy and schizophrenia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy | Altered CACNG4 expression may disrupt calcium channel function, leading to neuronal hyperexcitability. | ClinVar: Variants of uncertain significance; literature reports of altered expression in epileptic tissue. |
| Schizophrenia | Dysregulation of CACNG4 in the brain may affect glutamatergic signaling and synaptic function. | Expression studies show reduced CACNG4 mRNA in prefrontal cortex of schizophrenia patients (PubMed). |
| Bipolar Disorder | Potential involvement in calcium signaling pathways implicated in mood disorders. | GWAS and expression studies suggest association (PubMed). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High expression in multiple brain regions, especially cortex and hippocampus. |
| Testis | Moderate | Moderate expression in testis. |
| Adrenal Gland | Low | Low expression in adrenal gland. |
| Liver | Not detected | No significant expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal cell line with high CACNG4 expression. |
| U-87 MG (glioblastoma) | Moderate | Moderate expression in glial cells. |
| HEK293 (embryonic kidney) | Low | Low endogenous expression; used for heterologous expression studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.647C>T (p.Pro216Leu) | Missense | Rare | Potential impact on protein function; reported in epilepsy patients (ClinVar). |
| c.1045G>A (p.Val349Ile) | Missense | Rare | Uncertain significance; found in schizophrenia cohort (ClinVar). |
| c.1234A>G (p.Ile412Val) | Missense | Rare | Benign polymorphism (ClinVar). |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations may reduce calcium channel modulation, leading to altered neuronal excitability.
Gain of Function (GOF)
Gain-of-function mutations could enhance calcium influx, potentially causing excitotoxicity.
Dominant Negative (DN)
Dominant-negative effects may interfere with normal subunit assembly, disrupting channel function.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated calcium channel activity | • calcium ion binding |
| • plasma membrane | • integral component of membrane |
| • regulation of calcium ion transport | • nervous system development |
Pathways
• Voltage-gated calcium channel complex
• Calcium signaling pathway
• Synaptic transmission
• Neuronal system
Protein Summary
The CACNG4 protein is a type I transmembrane protein that associates with voltage-gated calcium channels, modulating their gating properties and trafficking. It is part of the gamma subunit family, which is primarily expressed in the central nervous system. CACNG4 influences calcium influx, thereby affecting neurotransmitter release, gene expression, and neuronal plasticity. Structural studies suggest it has a tetratricopeptide repeat (TPR) domain that mediates protein-protein interactions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNG4 Knockout HEK293 Cell Line | EDJ-KQ2982 | Human | 27092 | Details Get a Quote |
| CACNG4 Knockout A-549 Cell Line | EDJ-KQ24160 | Human | 27092 | Details Get a Quote |
| CACNG4 Knockout HeLa Cell Line | EDJ-KQ22788 | Human | 27092 | Details Get a Quote |
| CACNG4 Knockout HCT 116 Cell Line | EDJ-KQ72942 | Human | 27092 | Details Get a Quote |
