ORAI1
ORAI calcium release-activated calcium modulator 1, the group of ORAI calcium release-activated calcium modulators
Basic information
Region (hg38): 12:121626508-121643218
Previous symbols: [ "TMEM142A" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 (134 variants)
- Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency (129 variants)
- not provided (32 variants)
- not specified (13 variants)
- Combined immunodeficiency due to ORAI1 deficiency (5 variants)
- Myopathy, tubular aggregate, 2 (4 variants)
- ORAI1-related condition (2 variants)
- Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 1 (1 variants)
- Inborn genetic diseases (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.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 15 | 65 | 86 | |||
| missense | 137 | 147 | ||||
| nonsense | 5 | |||||
| start loss | 1 | |||||
| frameshift | 12 | 20 | ||||
| inframe indel | 10 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region ? | 3 | 1 | 4 | |||
| non coding ? | 10 | |||||
| Total | 3 | 7 | 181 | 75 | 14 |
Highest pathogenic variant AF is 0.0000329
Variants in ORAI1
This is a list of pathogenic ClinVar variants found in the ORAI1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-121626524-C-A | Likely benign (Sep 02, 2018) | |||
| 12-121626720-C-T | Likely benign (Apr 23, 2018) | |||
| 12-121626727-C-G | Uncertain significance (Jan 04, 2017) | |||
| 12-121626743-A-T | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Jan 16, 2024) | ||
| 12-121626747-A-G | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Nov 08, 2022) | ||
| 12-121626748-T-C | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Likely benign (Oct 26, 2023) | ||
| 12-121626748-T-G | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Uncertain significance (Jun 25, 2023) | ||
| 12-121626749-C-T | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Aug 09, 2018) | ||
| 12-121626750-C-T | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Uncertain significance (May 23, 2023) | ||
| 12-121626754-G-T | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Benign/Likely benign (Jan 31, 2024) | ||
| 12-121626755-C-G | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Uncertain significance (Jan 27, 2022) | ||
| 12-121626754-G-GCCCGC | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Jan 30, 2023) | ||
| 12-121626756-C-T | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 • not specified | Conflicting classifications of pathogenicity (Feb 16, 2024) | ||
| 12-121626759-C-T | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Jun 05, 2023) | ||
| 12-121626759-CC-TT | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Jul 26, 2022) | ||
| 12-121626760-C-T | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Uncertain significance (May 04, 2022) | ||
| 12-121626763-G-A | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Likely benign (Apr 23, 2023) | ||
| 12-121626764-C-T | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Jan 29, 2024) | ||
| 12-121626767-C-T | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Oct 21, 2022) | ||
| 12-121626773-C-T | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Uncertain significance (Mar 07, 2020) | ||
| 12-121626774-G-T | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Uncertain significance (May 06, 2022) | ||
| 12-121626776-A-C | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Sep 23, 2021) | ||
| 12-121626779-A-C | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (May 21, 2022) | ||
| 12-121626779-A-T | Myopathy, tubular aggregate, 2;Combined immunodeficiency due to ORAI1 deficiency | Uncertain significance (Jan 19, 2024) | ||
| 12-121626782-C-G | Combined immunodeficiency due to ORAI1 deficiency;Myopathy, tubular aggregate, 2 | Uncertain significance (Jan 08, 2024) |
GnomAD
Source:
dbNSFP
Source:
- 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
- ghis
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