ORAI1

ORAI calcium release-activated calcium modulator 1, the group of ORAI calcium release-activated calcium modulators

Basic information

Region (hg38): 12:121626509-121643218

Previous symbols: [ "TMEM142A" ]

Links

ENSG00000276045 ∙ NCBI:84876 ∙ OMIM:610277 ∙ HGNC:25896 ∙ Uniprot:Q96D31 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Stormorken syndrome (Supportive), mode of inheritance: AD
• tubular aggregate myopathy (Supportive), mode of inheritance: AD
• combined immunodeficiency due to ORAI1 deficiency (Supportive), mode of inheritance: AR
• combined immunodeficiency due to ORAI1 deficiency (Strong), mode of inheritance: AR
• myopathy, tubular aggregate, 2 (Strong), mode of inheritance: AD
• tubular aggregate myopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 9	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis; early and aggressive treatment of infections	Allergy/Immunology/Infectious; Musculoskeletal; Neurologic	8814256; 15452313; 16582901; 21873530; 24591628; 25227914

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ORAI1 gene.

• Myopathy, tubular aggregate, 2 (2 variants)
• Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency (2 variants)
• Combined immunodeficiency due to ORAI1 deficiency (2 variants)
• Myopathy with tubular aggregates (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ORAI1 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	97	6	113
missense	3	1	178	6	1	189
nonsense		2	3			5
start loss			1			1
frameshift	3	6	14	3	1	27
splice donor/acceptor (+/-2bp)			1			1
Total	6	9	207	106	8

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1 (PubMed:16582901, PubMed:16645049, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:19249086, PubMed:23307288, PubMed:24351972, PubMed:24591628, PubMed:28219928). CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT (PubMed:16582901). {ECO:0000269|PubMed:16582901, ECO:0000269|PubMed:16645049, ECO:0000269|PubMed:16733527, ECO:0000269|PubMed:16766533, ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:23307288, ECO:0000269|PubMed:24351972, ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:28219928}.
• Disease: DISEASE: Immunodeficiency 9 (IMD9) [MIM:612782]: An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, and normal lymphocytes counts and serum immunoglobulin levels. In surviving patients ectodermal dysplasia with anhidrosis and non-progressive myopathy may be observed. {ECO:0000269|PubMed:16147976, ECO:0000269|PubMed:16582901}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, tubular aggregate, 2 (TAM2) [MIM:615883]: A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. TAM2 patients have myopathy and pupillary abnormalities. {ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:28058752}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary immunodeficiency - Homo sapiens (human);Platelet activation - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Renin secretion - Homo sapiens (human);Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Signaling by the B Cell Receptor (BCR);Immune System;Adaptive Immune System;Ion homeostasis;Cardiac conduction;Muscle contraction;Hemostasis;Elevation of cytosolic Ca2+ levels;Platelet calcium homeostasis;Platelet homeostasis;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.486
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.49

Haploinsufficiency Scores

• pHI: 0.0975
• hipred: Y
• hipred_score: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.542

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Orai1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: orai1b
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: store-operated calcium entry;adaptive immune response;positive regulation of adenylate cyclase activity;regulation of calcium ion transport;positive regulation of calcium ion transport;mammary gland epithelium development;calcium ion import;calcium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;basolateral plasma membrane;protein-containing complex;plasma membrane raft;membrane raft
• Molecular function: protein binding;calmodulin binding;store-operated calcium channel activity;identical protein binding