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Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These 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, gene expression, cell motility, cell division and cell death. This gene encodes the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]
CACNA1E (Calcium Voltage-Gated Channel Subunit Alpha1 E) is a Protein Coding gene. Diseases associated with CACNA1E include Developmental And Epileptic Encephalopathy 69 and Developmental And Epileptic Encephalopathy. Among its related pathways are ERK Signaling and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include calcium ion binding and voltage-gated calcium channel activity. An important paralog of this gene is CACNA1A.
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.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH01J181486 | Promoter | 1.2 | EPDnew Ensembl | 250.1 | +165.4 | 165411 | 0.6 | ZNF341 EBF1 MAX TAF1 SPI1 BHLHE40 ZNF189 NRF1 RB1 IKZF1 | HSALNG0008872 HSALNG0008873 CACNA1E RF01045-014 ZNF648 | |
GH01J181318 | Enhancer | 0.6 | Ensembl | 250.7 | +0.8 | 768 | 0.5 | CTCF ZBTB48 EZH2 ZNF692 EGR2 ZBTB17 POLR2A GLIS2 PRDM10 ZBTB20 | CACNA1E HSALNG0008867 ZNF648 | |
GH01J181317 | Enhancer | 0.5 | Ensembl | 250.7 | -0.1 | -89 | 0.8 | REST EZH2 ZNF692 POLR2A PRDM10 ZBTB20 ZBTB26 ZNF335 | CACNA1E LOC107985454 IER5 | |
GH01J181484 | Promoter | 0.4 | EPDnew | 250.1 | +165.8 | 165808 | 0.1 | EZH2 | HSALNG0008872 HSALNG0008873 CACNA1E RF01045-014 ZNF648 | |
GH01J181319 | Enhancer | 0.4 | Ensembl | 250.7 | +1.2 | 1211 | 0.2 | EZH2 PRDM10 ZNF335 | CACNA1E HSALNG0008867 ZNF648 |
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 | IDA | 8071363 |
GO:0005262 | calcium channel activity | IEA | -- |
GO:0005509 | calcium ion binding | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005886 | plasma membrane | TAS | -- |
GO:0005891 | voltage-gated calcium channel complex | TAS,IEA | -- |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
GO:0045202 | synapse | 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 | Activation of cAMP-Dependent PKA |
Activation of cAMP-Dependent PKA
.77
cAMP Pathway
.77
|
PKA Signaling
.56
|
4 | CCR5 Pathway in Macrophages |
Androgen Signaling
.52
CCR5 Pathway in Macrophages
.52
|
Chemokine Signaling
.33
|
5 | Sweet Taste Signaling |
Melatonin Signaling
.72
Sweet Taste Signaling
.72
|
Cellular Effects of Sildenafil
.46
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006811 | ion transport | IEA | -- |
GO:0006816 | calcium ion transport | IBA | 21873635 |
GO:0007268 | chemical synaptic transmission | TAS,IBA | 21873635 |
GO:0034765 | regulation of ion transmembrane transport | IEA | -- |
GO:0050796 | regulation of insulin secretion | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Nitrendipine | Approved, Investigational | Pharma | Calcium channel blocker, Ca2+ channel blocker (L-type) | 8 | ||
Bioallethrin | Approved, Experimental | Pharma | Target, agonist | 0 | ||
Butamben | Approved, Withdrawn | Pharma | Target, inhibitor | 0 | ||
Calcium citrate | Approved, Investigational | Pharma | Transporter, substrate | 0 | ||
Calcium Phosphate | Approved | Pharma | Transporter, substrate | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
(+-)-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 |
---|---|---|
2-APB | 524-95-8 | |
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 |
Cilnidipine | Blocker of Dual L- and N-type calcium channel | 132203-70-4 |
Cinepazide maleate | 26328-04-1 | |
Clevidipine Butyrate | 167221-71-8 | |
Dehydroepiandrosterone (DHEA) | Endogenous steroid hormone | 53-43-0 |
Diltiazem HCl | 33286-22-5 | |
Felodipine | 72509-76-3 | |
Flunarizine 2HCl | Calcium entry blocker | 30484-77-6 |
Gabapentin HCl | GABA analog | 60142-95-2 |
Isradipine (Dynacirc) | Calcium channel blocker | 75695-93-1 |
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 | |
Nicardipine HCl | 54527-84-3 | |
Nilvadipine | 75530-68-6 | |
Nisoldipine | 63675-72-9 | |
Nitrendipine | Calcium channel blocker | 39562-70-4 |
Ranolazine 2HCl | Partial fatty acid oxidation inhibitor | 95635-56-6 |
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 |
Verapamil HCl | 152-11-4 | |
Zonisamide | Antiepileptic with anticonvulsant and mechanistic effect | 68291-97-4 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CACNA1E 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CAV2.3 31 |
|
OneToOne | |
CACNA1E 30 |
|
||||
Dog (Canis familiaris) |
Mammalia | CACNA1E 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Cacna1e 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Cacna1e 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | CACNA1E 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | CACNA1E 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | CACNA1E 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | CACNA1E 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | cacna1e 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | LOC564274 30 |
|
||
cacna1r 31 |
|
OneToMany | |||
CACNA1E (2 of 2) 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | cac 32 |
|
|
|
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
870847 | Pathogenic: not provided | 181,724,489(+) |
C/A NM_001205293.3(CACNA1E):c.2094C>A (p.Phe698Leu) |
MISSENSE | |
870848 | Uncertain Significance: not provided | 181,771,352(+) |
GA/G NM_001205293.3(CACNA1E):c.4942del (p.Ser1648fs) |
FRAMESHIFT | |
870849 | Uncertain Significance: not provided | 181,783,743(+) |
T/C NM_001205293.3(CACNA1E):c.5429T>C (p.Met1810Thr) |
MISSENSE | |
928919 | Uncertain Significance: not specified | 181,718,127(+) |
G/A NM_001205293.3(CACNA1E):c.1598G>A (p.Arg533His) |
MISSENSE | |
931176 | Uncertain Significance: Developmental and epileptic encephalopathy, 69 | 181,798,497(+) |
G/A NM_001205293.3(CACNA1E):c.6605G>A (p.Ser2202Asn) |
MISSENSE |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv2719984 | CNV | deletion | 23290073 |
esv2719995 | CNV | deletion | 23290073 |
esv2720006 | CNV | deletion | 23290073 |
esv3306940 | CNV | mobile element insertion | 20981092 |
esv3310337 | CNV | mobile element insertion | 20981092 |
esv3323984 | CNV | insertion | 20981092 |
esv3448829 | CNV | insertion | 20981092 |
esv3588086 | CNV | loss | 21293372 |
esv3588089 | CNV | loss | 21293372 |
nsv1144418 | CNV | deletion | 24896259 |
nsv477334 | CNV | novel sequence insertion | 20440878 |
nsv516290 | CNV | gain | 19592680 |
nsv517925 | CNV | loss | 19592680 |
Disorder | Aliases | PubMed IDs |
---|---|---|
developmental and epileptic encephalopathy 69 |
|
|
developmental and epileptic encephalopathy |
|
|
syndromic x-linked intellectual disability 94 |
|
|
inner ear disease |
|
|
fleck retina, familial benign |
|
|