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Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]
CACNA1A (Calcium Voltage-Gated Channel Subunit Alpha1 A) is a Protein Coding gene. Diseases associated with CACNA1A include Spinocerebellar Ataxia 6 and Episodic Ataxia, Type 2. Among its related pathways are Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction) and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include ion channel activity and voltage-gated calcium channel activity. An important paralog of this gene is CACNA1B.
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:0001540 | amyloid-beta binding | IC | 23376566 |
GO:0005216 | ion channel activity | IEA | -- |
GO:0005244 | voltage-gated ion channel activity | IEA | -- |
GO:0005245 | voltage-gated calcium channel activity | IEA,IGI | 21883149 |
GO:0005262 | calcium channel activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IDA | 16595610 |
GO:0005737 | cytoplasm | IDA | 16595610 |
GO:0005886 | plasma membrane | TAS | -- |
GO:0005891 | voltage-gated calcium channel complex | IEA | -- |
GO:0016020 | membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | DREAM Repression and Dynorphin Expression |
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 | Circadian entrainment | ||
4 | GABAergic synapse | ||
5 | Type II diabetes mellitus |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006811 | ion transport | IEA | -- |
GO:0006816 | calcium ion transport | IBA,IEA | 21873635 |
GO:0007204 | positive regulation of cytosolic calcium ion concentration | IDA | 10753886 |
GO:0007214 | gamma-aminobutyric acid signaling pathway | IEA | -- |
GO:0007268 | chemical synaptic transmission | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Bepridil | Approved, Withdrawn | Pharma | Pore Blocker, Target, inhibitor, blocker | 0 | ||
Pregabalin | Approved, Illicit, Investigational | Pharma | modulator | GABA analog/VDCC ligand;anticonvulsant/anxiolytic analgesic | 426 | |
Loperamide | Approved | Pharma | Target, inhibitor | 162 | ||
Amlodipine | Approved | Pharma | Target, blocker | Calcium channel blocker | 563 | |
Nisoldipine | Approved | Pharma | Gating inhibitor, blocker | 5 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
omega-agatoxin IVA |
|
Channel blocker |
|
|
||
omega-agatoxin IVB |
|
Channel blocker |
|
|
||
omega-conotoxin MVIIC |
|
Channel blocker |
|
|
||
O-Desmethylverapamil (D-702) |
|
|
||||
(+-)-Bay K 8644 |
|
71145-03-4 |
|
|
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 |
---|---|---|
(-)-Xestospongin C | 88903-69-9 | |
(R)-(+)-Bay K 8644 | 98791-67-4 | |
(S)-(-)-Bay K 8644 | 98625-26-4 | |
2-APB | 524-95-8 | |
A23187, free acid | Ca2+ ionophore | 52665-69-7 |
A-7 hydrochloride | 79127-24-5 | |
Amlodipine | Calcium channel blocker | 88150-42-9 |
Amlodipine Besylate | Block of L-type calcium channel | 111470-99-6 |
Azelnidipine | L-type calcium channel blocker;antihypertensive | 123524-52-7 |
Benidipine HCl | Calcium channel blocker | 91599-74-5 |
Bepridil hydrochloride | 68099-86-5 | |
Calmidazolium chloride | 57265-65-3 | |
CALP1 | 145224-99-3 | |
CALP2 | 261969-04-4 | |
CALP3 | 261969-05-5 | |
Camstatin | 1002295-95-5 | |
CGS 9343B | 109826-27-9 | |
Cilnidipine | Blocker of Dual L- and N-type calcium channel | 132203-70-4 |
Cinepazide maleate | 26328-04-1 | |
cis-Ned 19 | 1137264-00-6 | |
Clevidipine Butyrate | 167221-71-8 | |
Dantrolene, sodium salt | 14663-23-1 | |
Dehydroepiandrosterone (DHEA) | Endogenous steroid hormone | 53-43-0 |
DHBP dibromide | 6159-05-3 | |
Diltiazem HCl | 33286-22-5 | |
Efonidipine hydrochloride monoethanolate | 111011-76-8 | |
Felodipine | 72509-76-3 | |
Flunarizine 2HCl | Calcium entry blocker | 30484-77-6 |
FPL 64176 | 120934-96-5 | |
Gabapentin enacarbil | 478296-72-9 | |
Gabapentin HCl | GABA analog | 60142-95-2 |
Gadolinium chloride | 10138-52-0 | |
Huwentoxin XVI | N-type Ca2+ channel blocker,potent and selective | 1600543-88-1 |
Ionomycin calcium salt | ionophore | 56092-82-1 |
Ionomycin free acid | calcium ionophore | 56092-81-0 |
Isradipine (Dynacirc) | Calcium channel blocker | 75695-93-1 |
L-651,582 | 99519-84-3 | |
Lacidipine | L-type calcium channel blocker | 103890-78-4 |
Lomerizine HCl | 101477-54-7 | |
Manidipine | Calcium channel blocker | 89226-50-6 |
Manidipine 2HCl | 89226-75-5 | |
Mibefradil | Calcium channel blocker | 116644-53-2 |
ML 218 hydrochloride | 1346233-68-8 | |
MRS 1845 | 544478-19-5 | |
NAADP tetrasodium salt | 5502-96-5 | |
Nicardipine HCl | 54527-84-3 | |
Nilvadipine | 75530-68-6 | |
Nisoldipine | 63675-72-9 | |
Nitrendipine | Calcium channel blocker | 39562-70-4 |
NP118809 | N-type calcium channel blocker | 41332-24-5 |
Osthole | Antitumor reagent | 484-12-8 |
PD 173212 | 217171-01-2 | |
Pregabalin | GABA analog/VDCC ligand;anticonvulsant/anxiolytic analgesic | 148553-50-8 |
ProTx I | 484598-35-8 | |
Ranolazine 2HCl | Partial fatty acid oxidation inhibitor | 95635-56-6 |
Ruthenium Red | 11103-72-3 | |
Ryanodine | 15662-33-6 | |
SNX 482 | 203460-30-4 | |
SR 33805 oxalate | 121346-33-6 | |
STO-609 acetate | 1173022-21-3 | |
Strontium Ranelate | 135459-87-9 | |
Tetracaine HCl | Anaesthetic and allosteric inhibitor | 136-47-0 |
Tetrandrine | 518-34-3 | |
Thioridazine HCl | Calcium channel protein inhibitor | 130-61-0 |
trans-Ned 19 | 1354235-96-3 | |
Verapamil HCl | 152-11-4 | |
W-13 hydrochloride | 88519-57-7 | |
W-5 hydrochloride | 61714-25-8 | |
W-7 hydrochloride | 61714-27-0 | |
W-9 hydrochloride | 69762-85-2 | |
YM 58483 | 223499-30-7 | |
Zonisamide | Antiepileptic with anticonvulsant and mechanistic effect | 68291-97-4 |
Zonisamide sodium | 68291-98-5 | |
ω-Agatoxin IVA | 145017-83-0 | |
ω-Agatoxin TK | 158484-42-5 | |
ω-Conotoxin GVIA | 106375-28-4 | |
ω-Conotoxin MVIIC | 147794-23-8 |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
chimpanzee (Pan troglodytes) |
Mammalia | CACNA1A 33 32 |
|
OneToOne | |
platypus (Ornithorhynchus anatinus) |
Mammalia | -- 33 |
|
OneToMany | |
-- 33 |
|
OneToMany | |||
-- 33 |
|
OneToMany | |||
dog (Canis familiaris) |
Mammalia | CACNA1A 33 32 |
|
OneToOne | |
cow (Bos Taurus) |
Mammalia | CACNA1A 33 32 |
|
OneToOne | |
mouse (Mus musculus) |
Mammalia | Cacna1a 17 33 32 |
|
||
rat (Rattus norvegicus) |
Mammalia | Cacna1a 32 |
|
||
oppossum (Monodelphis domestica) |
Mammalia | CACNA1A 33 |
|
OneToOne | |
lizard (Anolis carolinensis) |
Reptilia | -- 33 |
|
OneToMany | |
-- 33 |
|
OneToMany | |||
tropical clawed frog (Silurana tropicalis) |
Amphibia | cacna1a 32 |
|
||
zebrafish (Danio rerio) |
Actinopterygii | cacna1aa 33 |
|
OneToMany | |
cacna1ab 33 32 |
|
OneToMany | |||
fruit fly (Drosophila melanogaster) |
Insecta | cac 34 |
|
|
|
rice (Oryza sativa) |
Liliopsida | Os.46813 32 |
|
||
sea squirt (Ciona savignyi) |
Ascidiacea | -- 33 |
|
OneToMany |
SNP ID | Clin | Chr 19 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs1001063428 | uncertain-significance, Epileptic encephalopathy, early infantile, 42, Episodic ataxia type 2 | 13,228,737(-) | C/T | coding_sequence_variant, intron_variant, missense_variant | |
rs1005732031 | uncertain-significance, Epileptic encephalopathy, early infantile, 42, Episodic ataxia type 2 | 13,365,356(-) | T/C | coding_sequence_variant, missense_variant | |
rs1013100046 | uncertain-significance, Epileptic encephalopathy, early infantile, 42, Episodic ataxia type 2 | 13,359,752(-) | C/A/T | coding_sequence_variant, missense_variant | |
rs1021438528 | uncertain-significance, History of neurodevelopmental disorder | 13,208,806(-) | G/A | coding_sequence_variant, missense_variant | |
rs1034627495 | uncertain-significance, Epileptic encephalopathy, early infantile, 42, Episodic ataxia type 2 | 13,231,707(-) | C/T | intron_variant |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv1022e212 | CNV | loss | 25503493 |
dgv1713n106 | CNV | deletion | 24896259 |
dgv1714n106 | CNV | tandem duplication | 24896259 |
dgv3438n100 | CNV | gain | 25217958 |
esv1689364 | CNV | insertion | 17803354 |
esv2665817 | CNV | deletion | 23128226 |
esv2718201 | CNV | deletion | 23290073 |
esv2718202 | CNV | deletion | 23290073 |
esv3307138 | CNV | mobile element insertion | 20981092 |
esv3345059 | CNV | insertion | 20981092 |
esv34036 | CNV | loss | 18971310 |
esv3414118 | CNV | duplication | 20981092 |
esv3429165 | CNV | insertion | 20981092 |
esv3643722 | CNV | loss | 21293372 |
esv4302 | CNV | loss | 18987735 |
esv7746 | CNV | gain | 19470904 |
nsv1062073 | CNV | gain | 25217958 |
nsv1071509 | CNV | deletion | 25765185 |
nsv1072861 | CNV | deletion | 25765185 |
nsv1125668 | CNV | tandem duplication | 24896259 |
nsv1126513 | CNV | deletion | 24896259 |
nsv138156 | CNV | insertion | 16902084 |
nsv138168 | CNV | deletion | 16902084 |
nsv510468 | OTHER | sequence alteration | 20534489 |
nsv520548 | CNV | loss | 19592680 |
nsv523990 | CNV | loss | 19592680 |
nsv525967 | CNV | gain | 19592680 |
nsv819328 | CNV | loss | 19587683 |
nsv833755 | CNV | gain | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
spinocerebellar ataxia 6 |
|
|
episodic ataxia, type 2 |
|
|
epileptic encephalopathy, early infantile, 42 |
|
|
migraine, familial hemiplegic, 1 |
|
|
sporadic hemiplegic migraine |
|
|