TISIDB

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Multi-pass membrane protein Note=Isoform beta is more mobile in the plasma membrane (PubMed:23307288). Colocalizes with STIM1 at the cell membrane (PubMed:27185316).
Domain	PF07856 Mediator of CRAC channel activity
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).

> Gene Ontology [ TOP ]
Biological Process	GO:0002115 store-operated calcium entry GO:0002250 adaptive immune response GO:0006816 calcium ion transport GO:0010959 regulation of metal ion transport GO:0043270 positive regulation of ion transport GO:0051924 regulation of calcium ion transport GO:0051928 positive regulation of calcium ion transport GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0072511 divalent inorganic cation transport
Molecular Function	GO:0005216 ion channel activity GO:0005261 cation channel activity GO:0005262 calcium channel activity GO:0005516 calmodulin binding GO:0015085 calcium ion transmembrane transporter activity GO:0015267 channel activity GO:0015279 store-operated calcium channel activity GO:0022803 passive transmembrane transporter activity GO:0022838 substrate-specific channel activity GO:0046873 metal ion transmembrane transporter activity GO:0072509 divalent inorganic cation transmembrane transporter activity
Cellular Component	GO:0005776 autophagosome

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04020 Calcium signaling pathway hsa04024 cAMP signaling pathway hsa04611 Platelet activation
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983695: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers R-HSA-5576891: Cardiac conduction R-HSA-139853: Elevation of cytosolic Ca2+ levels R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-5578775: Ion homeostasis R-HSA-397014: Muscle contraction R-HSA-418360: Platelet calcium homeostasis R-HSA-418346: Platelet homeostasis R-HSA-983705: Signaling by the B Cell Receptor (BCR)

> KEGG and Reactome Pathway

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KEGG

hsa04020 Calcium signaling pathway
hsa04024 cAMP signaling pathway
hsa04611 Platelet activation

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-983695: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-5576891: Cardiac conduction
R-HSA-139853: Elevation of cytosolic Ca2+ levels
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-5578775: Ion homeostasis
R-HSA-397014: Muscle contraction
R-HSA-418360: Platelet calcium homeostasis
R-HSA-418346: Platelet homeostasis
R-HSA-983705: Signaling by the B Cell Receptor (BCR)

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ORAI1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between ORAI1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23922331	Melanoma; Colon Carcinoma	Promote immunity	Patients with loss-of-function mutations in the CRAC channel genes ORAI1 or STIM1 are immunodeficient and are prone to develop virus-associated tumours. Using conditional knock out mice lacking STIM1 and its homologue STIM2, we find that SOCE in CD8(+) T cells is required to prevent the engraftment of melanoma and colon carcinoma cells and to control tumour growth.

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of ORAI1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of ORAI1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.134	0.7
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.444	0.85
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.098	0.952
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.319	0.427
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.082	0.951
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.831	0.642
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.161	0.637
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.011	0.993
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.274	0.844
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.06	0.463

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ORAI1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ORAI1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ORAI1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ORAI1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ORAI1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ORAI1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ORAI1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ORAI1
Name	ORAI calcium release-activated calcium modulator 1
Aliases	FLJ14466; CRACM1; calcium release-activated calcium modulator 1; TMEM142A; transmembrane protein 142A; IMD9; ......
Chromosomal Location	12q24.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ORAI1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse ORAI1