CACNG3 (Calcium Channel Gamma 3) is a gene involved in various cellular functions relevant to neuronal health and neurodegenerative diseases. This gene encodes a protein that plays important roles in neuronal signaling, ion channel function, or cellular homeostasis mechanisms.
Gene Symbol: CACNG3
Gene Name: Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 3
Chromosomal Location: 16p12.1
NCBI Gene ID: 10368
Ensembl ID: ENSG00000106443
UniProt ID: Q9Y698
CACNG3 encodes the voltage-dependent calcium channel gamma-3 subunit (CaB2), an auxiliary component of L-type voltage-gated calcium channels (VGCCs). The gamma subunits are transmembrane proteins that modulate channel trafficking, gating, and voltage dependence[1].
The CACNG3 protein associates with the main pore-forming alpha subunit (primarily Cav1.2 and Cav1.3 channels) and modulates:
In the brain, CACNG3 is expressed in regions important for synaptic plasticity and neuronal excitability. The gamma-3 subunit influences calcium influx during synaptic activity, affecting:
CACNG3 mutations have been linked to childhood epilepsy syndromes, including absence seizures and generalized tonic-clonic seizures. Dysregulated calcium influx contributes to neuronal hyperexcitability[3].
Impaired calcium channel function in cerebellar Purkinje cells can lead to ataxia. CACNG3 variants may contribute to cerebellar ataxia phenotypes[4].
Given the role of calcium signaling in synaptic development and function, CACNG3 has been investigated as a candidate gene for autism. Copy number variations and rare variants have been reported[5].
L-type calcium channel function is relevant to cortical spreading depression in migraine. CACNG3 variants may modify migraine susceptibility[6].
| Tissue | Expression Level |
|---|---|
| Cerebral cortex | High |
| Hippocampus | Moderate |
| Cerebellum | Moderate |
| Thalamus | High |
| Heart | Low |
| Skeletal muscle | Low |
| Variant | Type | Significance |
|---|---|---|
| R101Q | Missense | Pathogenic - Epilepsy |
| V138M | Missense | Risk factor - Ataxia |
| E200K | Missense | Pathogenic - ASD |
A E. Clin Exp Pharmacol. 2012;2(5):1000112. 2012. ↩︎
Cheng CF, et al. Calcium channel gamma subunits. Cell Mol Life Sci. 2011. ↩︎
Calame DJ, et al. CACNG3 and epilepsy. Ann Neurol. 2012. ↩︎
Kordas C, et al. Calcium channel subunits in ataxia. Cerebellum. 2015. ↩︎
Gong X, et al. CACNG3 in autism. Mol Autism. 2012. ↩︎
Waeber C, et al. Calcium channels and migraine. Biochim Biophys Acta. 1999. ↩︎