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The protein encoded by this gene is a membrane calcium channel subunit that is activated by the calcium sensor STIM1 when calcium stores are depleted. This type of channel is the primary way for calcium influx into T-cells. Defects in this gene are a cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 1 (IDTICED1). [provided by RefSeq, Sep 2011]
ORAI1 (ORAI Calcium Release-Activated Calcium Modulator 1) is a Protein Coding gene. Diseases associated with ORAI1 include Immunodeficiency 9 and Myopathy, Tubular Aggregate, 2. Among its related pathways are Platelet homeostasis and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include identical protein binding and store-operated calcium channel activity. An important paralog of this gene is ORAI3.
STIM-Orai channels have recently been identified as the underlying molecular mechanism of store-operated calcium entry (SOCE). STIM (stromal interaction molecule) proteins are ER Ca2+ sensors. Orai proteins are STIM binding partners that form the channel pore.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005262 | calcium channel activity | IEA,IDA | 31009446 |
GO:0005515 | protein binding | IPI | 17360584 |
GO:0005516 | calmodulin binding | IEA | -- |
GO:0015279 | store-operated calcium channel activity | IDA | 16645049 |
GO:0042802 | identical protein binding | IPI | 18757751 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005829 | cytosol | IDA | -- |
GO:0005886 | plasma membrane | IEA,IDA | 19171672 |
GO:0005887 | integral component of plasma membrane | IDA | 16645049 |
GO:0016020 | membrane | IBA | 21873635 |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Aldosterone synthesis and secretion |
.41
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2 | Cardiac conduction |
.39
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3 | Platelet homeostasis | ||
4 | TCR signaling in naive CD4+ T cells | ||
5 | Calcium signaling pathway |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002115 | store-operated calcium entry | IBA,IDA | 28219928 |
GO:0002250 | adaptive immune response | IEA | -- |
GO:0002376 | immune system process | IEA | -- |
GO:0006811 | ion transport | IEA | -- |
GO:0006816 | calcium ion transport | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
2-APB | Pharma | Channel blocker, Pore Blocker, Antagonist, Gating inhibitor, Activator, Agonist, Potentiation | IP3 receptor antagonist. Also TRP channel modulator | 0 | ||
ML 9 hydrochloride | Pharma | Myosin light chain kinase inhibitor | 0 | |||
SKF 96365 hydrochloride | Pharma | SOCE inhibitor, TRPC channel blocker; also inhibits store-operated Ca2+ entry | 0 | |||
YM 58483 | Pharma | Inhibitor of SOCE in non-excitable cells | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
5J 4 |
|
827001-82-1 |
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|
Compound | Action | Cas Number |
---|---|---|
2-APB | IP3 receptor antagonist. Also TRP channel modulator | 524-95-8 |
5J 4 | CRAC channel blocker; anti-inflammatory | 827001-82-1 |
ML 9 hydrochloride | Myosin light chain kinase inhibitor | 105637-50-1 |
SKF 96365 hydrochloride | TRPC channel blocker; also inhibits store-operated Ca2+ entry | 130495-35-1 |
YM 58483 | Inhibitor of SOCE in non-excitable cells | 223499-30-7 |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | ORAI1 30 |
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Cow (Bos Taurus) |
Mammalia | ORAI1 30 |
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Dog (Canis familiaris) |
Mammalia | ORAI1 30 |
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||
Mouse (Mus musculus) |
Mammalia | Orai1 30 17 |
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Rat (Rattus norvegicus) |
Mammalia | Orai1 30 |
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||
Chicken (Gallus gallus) |
Aves | ORAI1 30 |
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||
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | orai2 30 |
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Str.15128 30 |
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African clawed frog (Xenopus laevis) |
Amphibia | Xl.23967 30 |
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||
Zebrafish (Danio rerio) |
Actinopterygii | LOC566671 30 |
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||
Dr.25945 30 |
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||||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.8801 30 |
|
SNP ID | Clinical significance and condition | Chr 12 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
639606 | Likely Pathogenic: Combined immunodeficiency due to ORAI1 deficiency; Myopathy, tubular aggregate, 2 | 121,641,282(+) | TC/T | FRAMESHIFT_VARIANT | |
644104 | Uncertain Significance: Combined immunodeficiency due to ORAI1 deficiency; Myopathy, tubular aggregate, 2 | 121,626,748(+) | T/G | MISSENSE_VARIANT | |
650573 | Uncertain Significance: Combined immunodeficiency due to ORAI1 deficiency; Myopathy, tubular aggregate, 2 | 121,626,852(+) | GGGAGCCCCC/G | INFRAME_DELETION | |
652118 | Uncertain Significance: Combined immunodeficiency due to ORAI1 deficiency; Myopathy, tubular aggregate, 2; not provided | 121,626,779(+) | A/T | MISSENSE_VARIANT | |
660638 | Uncertain Significance: Combined immunodeficiency due to ORAI1 deficiency; Myopathy, tubular aggregate, 2 | 121,626,856(+) | G/T | MISSENSE_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3630950 | CNV | loss | 21293372 |
esv3630951 | CNV | gain | 21293372 |
nsv1053272 | CNV | gain | 25217958 |
nsv1131048 | CNV | deletion | 24896259 |
nsv560458 | CNV | loss | 21841781 |
Disorder | Aliases | PubMed IDs |
---|---|---|
immunodeficiency 9 |
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myopathy, tubular aggregate, 2 |
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stormorken syndrome |
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myopathy, tubular aggregate, 1 |
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ectodermal dysplasia |
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