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This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
CACNA1S (Calcium Voltage-Gated Channel Subunit Alpha1 S) is a Protein Coding gene. Diseases associated with CACNA1S include Hypokalemic Periodic Paralysis, Type 1 and Malignant Hyperthermia 5. Among its related pathways are Beta-Adrenergic Signaling and ERK Signaling. Gene Ontology (GO) annotations related to this gene include ion channel activity and high voltage-gated calcium channel activity. An important paralog of this gene is CACNA1C.
Voltage-gated calcium channels (CaV) are present in the membrane of most excitable cells and mediate calcium influx in response to depolarization. They regulate intracellular processes such as contraction, secretion, neurotransmission and gene expression.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005216 | ion channel activity | IEA | -- |
GO:0005244 | voltage-gated ion channel activity | IEA | -- |
GO:0005245 | voltage-gated calcium channel activity | IEA,IDA | 9852570 |
GO:0005262 | calcium channel activity | IEA | -- |
GO:0005515 | protein binding | IPI | 25416956 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IDA | 11206130 |
GO:0005886 | plasma membrane | TAS | -- |
GO:0005891 | voltage-gated calcium channel complex | IEA,IDA | 9852570 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | nNOS Signaling in Skeletal Muscle |
BMP Pathway
.44
DREAM Repression and Dynorphin Expression
.44
nNOS Signaling in Skeletal Muscle
.37
|
Caspase Cascade
.36
Calpain Protease Regulates Cellular Mechanics
.31
|
2 | TCR Signaling (Qiagen) |
PKC-Theta Pathway
.68
TCR Signaling
.68
ITK and TCR Signaling
.54
|
Fc-EpsilonRI Pathway
.49
PDGF Pathway
.39
|
3 | Aldosterone synthesis and secretion |
.41
|
|
4 | Activation of cAMP-Dependent PKA |
Activation of cAMP-Dependent PKA
.77
cAMP Pathway
.77
|
PKA Signaling
.56
|
5 | CCR5 Pathway in Macrophages |
Androgen Signaling
.52
CCR5 Pathway in Macrophages
.52
|
Chemokine Signaling
.33
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006811 | ion transport | IEA | -- |
GO:0006816 | calcium ion transport | IEA,IDA | 9852570 |
GO:0006936 | muscle contraction | IMP | 17418573 |
GO:0034765 | regulation of ion transmembrane transport | IEA | -- |
GO:0055085 | transmembrane transport | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Nifedipine | Approved | Pharma | Channel blocker, Target, inhibitor, blocker | 150 | ||
Felodipine | Approved, Investigational | Pharma | Target, inhibitor, blocker | 24 | ||
Verapamil | Approved | Pharma | Channel blocker, blocker | 143 | ||
Nimodipine | Approved, Investigational | Pharma | Target, inhibitor | Ca2+ channel blocker (L-type) | 43 | |
Nitrendipine | Approved, Investigational | Pharma | Target, inhibitor | Calcium channel blocker, Ca2+ channel blocker (L-type) | 8 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
O-Desmethylverapamil (D-702) |
|
|||||
(+-)-Bay K 8644 |
|
71145-03-4 |
|
|
||
Verapamil hydrochloride |
|
152-11-4 |
|
|
Compound | Action | Cas Number |
---|---|---|
(+-)-Bay K 8644 | Ca2+ channel activator (L-type) | 71145-03-4 |
Nimodipine | Ca2+ channel blocker (L-type) | 66085-59-4 |
Nitrendipine | Ca2+ channel blocker (L-type) | 39562-70-4 |
Ruthenium Red | Non-selective Ca2+ channel blocker (N- and P-type) | 11103-72-3 |
Verapamil hydrochloride | Ca2+ channel blocker (L-type) | 152-11-4 |
Compound | Action | Cas Number |
---|---|---|
Amlodipine Besylate | Block of L-type calcium channel | 111470-99-6 |
Azelnidipine | L-type calcium channel blocker;antihypertensive | 123524-52-7 |
Lacidipine | L-type calcium channel blocker | 103890-78-4 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CACNA1S 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | CACNA1S 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Cacna1s 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Cacna1s 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | CACNA1S 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CACNA1S 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | CACNA1S 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | CACNA1S 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | CACNA1S 31 |
|
OneToOne | |
African clawed frog (Xenopus laevis) |
Amphibia | Xl.11094 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | cacna1sa 30 31 |
|
OneToMany | |
cacna1sb 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | Ca-alpha1D 31 32 |
|
OneToOne | |
Worm (Caenorhabditis elegans) |
Secernentea | egl-19 31 32 |
|
OneToOne | |
unc-2 32 |
|
|
|||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
834688 | Uncertain Significance: Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis 1 | 201,062,065(-) |
C/T NM_000069.3(CACNA1S):c.2932G>A (p.Gly978Arg) |
MISSENSE | |
836844 | Uncertain Significance: Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis 1 | 201,047,167(-) |
C/T NM_000069.3(CACNA1S):c.4616G>A (p.Arg1539His) |
MISSENSE | |
837079 | Uncertain Significance: Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis 1 | 201,040,698(-) |
G/C NM_000069.3(CACNA1S):c.5150C>G (p.Pro1717Arg) |
MISSENSE | |
838690 | Uncertain Significance: Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis 1 | 201,091,769(-) |
T/C NM_000069.3(CACNA1S):c.565A>G (p.Ile189Val) |
MISSENSE | |
838843 | Uncertain Significance: Malignant hyperthermia, susceptibility to, 5; Hypokalemic periodic paralysis 1 | 201,048,604(-) |
C/T NM_000069.3(CACNA1S):c.4419G>A (p.Thr1473=) |
SYNONYMOUS |
Disorder | Aliases | PubMed IDs |
---|---|---|
hypokalemic periodic paralysis, type 1 |
|
|
malignant hyperthermia 5 |
|
|
thyrotoxic periodic paralysis 1 |
|
|
malignant hyperthermia |
|
|
periodic paralysis with transient compartment-like syndrome |
|
|