ORAI calcium release-activated calcium modulator 1
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Diagnostic Grade (Green)
Amelogenesis imperfecta
BIALLELIC, autosomal or pseudoautosomalArthrogryposis
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownCongenital myopathy
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownCOVID-19 research
BIALLELIC, autosomal or pseudoautosomalLimb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownPrimary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomalFetal anomalies
BOTH monoallelic and biallelic, autosomal or pseudoautosomalInherited bleeding disorders
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownmyopathy, tubular aggregate, 2
combined immunodeficiency due to ORAI1 deficiency
tubular aggregate myopathy
severe combined immunodeficiency
combined immunodeficiency
T-B- severe combined immunodeficiency
T-B+ severe combined immunodeficiency
Stormorken-Sjaastad-Langslet syndrome
myopathy, tubular aggregate, 1
combined immunodeficiency due to CRAC channel dysfunction
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Calcium release-activated calcium channel protein 1
Pore-forming subunit of two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels (Probable) (PubMed:16645049, PubMed:16733527, PubMed:16807233, PubMed:16921383, PubMed:19249086, PubMed:19706554, PubMed:23307288, PubMed:26956484, PubMed:28219928). Assembles with ORAI2 and ORAI3 to form hexameric CRAC channels that mediate Ca(2+) influx upon depletion of endoplasmic reticulum Ca(2+) store and channel activation by Ca(2+) sensor STIM1, a process known as store-operated Ca(2+) entry (SOCE). Various pore subunit combinations may account for distinct CRAC channel spatiotemporal and cell-type specific dynamics. ORAI1 mainly contributes to the generation of Ca(2+) plateaus involved in sustained Ca(2+) entry and is dispensable for cytosolic Ca(2+) oscillations, whereas ORAI2 and ORAI3 generate oscillatory patterns. CRAC channels assemble in Ca(2+) signaling microdomains where Ca(2+) influx is coupled to calmodulin and calcineurin signaling and activation of NFAT transcription factors recruited to ORAI1 via AKAP5. Activates NFATC2/NFAT1 and NFATC3/NFAT4-mediated transcriptional responses. CRAC channels are the main pathway for Ca(2+) influx in T cells and promote the immune response to pathogens by activating NFAT-dependent cytokine and chemokine transcription (PubMed:16582901, PubMed:17442569, PubMed:19182790, PubMed:20354224, PubMed:22641696, PubMed:26221052, PubMed:32415068, PubMed:33941685). Assembles with ORAI3 to form channels that mediate store-independent Ca(2+) influx in response to inflammatory metabolites arachidonate or its derivative leukotriene C4, termed ARC and LRC channels respectively (PubMed:19622606, PubMed:32415068). Plays a prominent role in Ca(2+) influx at the basolateral membrane of mammary epithelial cells independently of the Ca(2+) content of endoplasmic reticulum or Golgi stores. May mediate transepithelial transport of large quantities of Ca(2+) for milk secretion (By similarity) (PubMed:20887894)
ORAI1 · Q96D31
Mean pLDDT
71.3/ 100
Confident
301 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
