CACNA1S
Calcium Voltage-Gated Channel Subunit Alpha1 S
Gene Information Card
| Symbol | CACNA1S |
|---|---|
| Full Name | Calcium Voltage-Gated Channel Subunit Alpha1 S |
| Gene Type | protein-coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 779 ncbi.nlm.nih.gov/gene/779 |
| Ensembl ID | ENSG00000081248 |
| UniProt ID | Q13698 |
| OMIM ID | 114208 |
| HGNC ID | 1397 |
| Aliases | CACNL1A3, Cav1.1, DHPR, HOKPP, MHS5, TTPP1 |
Description
The CACNA1S gene encodes the alpha-1S subunit of the voltage-dependent L-type calcium channel (Cav1.1), primarily expressed in skeletal muscle. This subunit forms the pore and voltage sensor of the channel, which is essential for excitation-contraction coupling by mediating calcium influx and triggering calcium release from the sarcoplasmic reticulum.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypokalemic Periodic Paralysis (HOKPP) | Missense mutations in CACNA1S alter voltage sensing, leading to abnormal channel inactivation and episodic muscle weakness triggered by low potassium levels. | ClinVar, OMIM #114208 |
| Malignant Hyperthermia Susceptibility (MHS5) | Gain-of-function mutations cause excessive calcium release from sarcoplasmic reticulum during anesthesia, leading to hypermetabolic crisis. | ClinVar, OMIM #601887 |
| Thyrotoxic Periodic Paralysis (TPP) | Similar mechanism to HOKPP, often triggered by hyperthyroidism; CACNA1S variants may predispose. | OMIM #188580 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 82.5 | High |
| Heart | 0.3 | Not detected |
| Brain | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myotubes | 85.0 | High expression in differentiated muscle cells |
| HEK293 | 0.0 | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg528His | Missense | Rare | Associated with hypokalemic periodic paralysis; alters voltage sensor function. |
| p.Arg1239His | Missense | Rare | Associated with malignant hyperthermia susceptibility; gain-of-function. |
| p.Thr704Met | Missense | Rare | Associated with hypokalemic periodic paralysis; impairs channel inactivation. |
Mutation functional classification
Loss of Function (LOF)
Mutations causing hypokalemic periodic paralysis often result in reduced calcium current or altered voltage dependence, leading to loss of normal channel function.
Gain of Function (GOF)
Mutations associated with malignant hyperthermia (e.g., p.Arg1239His) enhance calcium channel activity, causing excessive calcium release.
Dominant Negative (DN)
Some HOKPP mutations may exert dominant-negative effects by disrupting channel assembly or function in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated calcium channel activity | • calcium ion binding |
| • calcium channel complex | • plasma membrane |
| • excitation-contraction coupling | • skeletal muscle contraction |
Pathways
• Excitation-contraction coupling in skeletal muscle
• Voltage-gated calcium channel pathway
• Calcium signaling pathway
Protein Summary
The Cav1.1 protein (alpha-1S subunit) is a 1873-amino acid transmembrane protein that forms the pore of the L-type calcium channel in skeletal muscle. It acts as a voltage sensor and directly interacts with the ryanodine receptor (RyR1) to trigger calcium release from the sarcoplasmic reticulum, essential for muscle contraction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CACNA1S Knockout HEK293 Cell Line | EDJ-KQ621 | Human | 779 | Details Get a Quote |
| CACNA1S Knockout HeLa Cell Line | EDJ-KQ52774 | Human | 779 | Details Get a Quote |
| CACNA1S Knockout A-549 Cell Line | EDJ-KQ61241 | Human | 779 | Details Get a Quote |
| CACNA1S Knockout HCT 116 Cell Line | EDJ-KQ69740 | Human | 779 | Details Get a Quote |
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