CACNA1C: Calcium Voltage-Gated Channel Subunit Alpha1 C
A critical gene encoding the pore-forming subunit of L-type calcium channels, implicated in cardiac, neuronal, and psychiatric disorders.
Gene Information Card
| Symbol | CACNA1C |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Subunit Alpha1 C |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.33 |
| NCBI Gene ID | 775 ncbi.nlm.nih.gov/gene/775 |
| Ensembl ID | ENSG00000151067 |
| UniProt ID | Q13936 |
| OMIM ID | 114205 |
| HGNC ID | 1390 |
| Aliases | CACH2, CACN2, CACNL1A1, CCHL1A1, Cav1.2, LQT8, TS |
Description
The CACNA1C gene encodes the alpha-1C subunit of the L-type voltage-gated calcium channel (Cav1.2), which mediates calcium influx in response to membrane depolarization. This channel is essential for cardiac action potential plateau, excitation-contraction coupling in cardiac and smooth muscle, and neuronal signaling. Mutations in CACNA1C are associated with Timothy syndrome, long QT syndrome type 8, Brugada syndrome, and various neuropsychiatric disorders including autism and schizophrenia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Timothy syndrome | Gain-of-function mutations in CACNA1C cause delayed channel inactivation, leading to prolonged calcium influx and multisystem dysfunction including cardiac arrhythmia and syndactyly. | ClinVar, OMIM |
| Long QT syndrome type 8 (LQT8) | Gain-of-function mutations prolong cardiac action potential duration by increasing calcium current, predisposing to torsades de pointes and sudden cardiac death. | ClinVar, OMIM |
| Brugada syndrome | Loss-of-function mutations reduce calcium current, contributing to ST-segment elevation and risk of ventricular fibrillation. | ClinVar, OMIM |
| Autism spectrum disorder | Rare variants in CACNA1C are associated with altered neuronal calcium signaling and synaptic plasticity. | NCBI, ClinVar |
| Schizophrenia | Common and rare variants in CACNA1C increase risk through dysregulation of calcium-dependent neuronal processes. | NCBI, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 45.2 | High |
| Brain | 28.7 | Medium |
| Smooth muscle | 22.1 | Medium |
| Pancreas | 8.3 | Low |
| Liver | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes | 62.5 | High expression in ventricular myocytes |
| Neurons (cortical) | 35.8 | High in excitatory neurons |
| Smooth muscle cells | 18.4 | Moderate expression |
| HEK293 | 0.5 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G406R | Missense | Rare | Gain-of-function; causes Timothy syndrome |
| G402S | Missense | Rare | Gain-of-function; causes Timothy syndrome |
| A39V | Missense | Rare | Loss-of-function; associated with Brugada syndrome |
| E1784K | Missense | Rare | Gain-of-function; causes LQT8 |
| rs1006737 | Intronic | Common (allele frequency ~0.3) | Risk variant for schizophrenia and bipolar disorder |
Mutation functional classification
Loss of Function (LOF)
Reduced calcium current, leading to Brugada syndrome and cardiac conduction defects.
Gain of Function (GOF)
Prolonged channel opening, causing Timothy syndrome and long QT syndrome type 8.
Dominant Negative (DN)
Not well documented for CACNA1C; most mutations act via gain- or loss-of-function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• L-type calcium channel pathway (Reactome: R-HSA-5576892)
• Cardiac conduction (Reactome: R-HSA-5576891)
• Calcium signaling pathway (KEGG: hsa04020)
• cAMP signaling pathway (KEGG: hsa04024)
Protein Summary
The Cav1.2 protein (UniProt Q13936) is a 2171-amino acid transmembrane protein that forms the pore of L-type calcium channels. It consists of four homologous domains (I-IV), each with six transmembrane segments. The alpha-1C subunit determines channel voltage sensitivity and ion selectivity. Cav1.2 is highly expressed in cardiac and smooth muscle, and in the brain, where it regulates excitation-contraction coupling, gene expression, and neurotransmitter release.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNA1C Knockout HEK293 Cell Line | EDJ-KQ615 | Human | 775 | Details Get a Quote |
| CACNA1C Knockout A-549 Cell Line | EDJ-KQ26286 | Human | 775 | Details Get a Quote |
| CACNA1C Knockout Hep-G2 Cell Line | EDJ-KZ126 | Human | 775 | Details Get a Quote |
| CACNA1C Knockout HeLa Cell Line | EDJ-KQ52770 | Human | 775 | Details Get a Quote |
| CACNA1C Knockout HCT 116 Cell Line | EDJ-KQ69736 | Human | 775 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
