TISIDB

Summary
Symbol	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
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	Isoform 1: Cell membrane Single-pass type I membrane protein Late endosome Lysosome Note=Interferon binding triggers internalization of the receptor from the cell membrane into endosomes and then into lysosomes.
Domain	PF09294 Interferon-alpha/beta receptor PF01108 Tissue factor
Function	Component of the receptor for type I interferons, including interferons alpha, IFNB1 and IFNW1 (PubMed:2153461, PubMed:7665574, PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:21854986). Functions in general as heterodimer with IFNAR2 (PubMed:7665574, PubMed:10049744, PubMed:21854986). Type I interferon binding activates the JAK-STAT signaling cascade, and triggers tyrosine phosphorylation of a number of proteins including JAKs, TYK2, STAT proteins and the IFNR alpha- and beta-subunits themselves (PubMed:7665574, PubMed:21854986). Can form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0001959 regulation of cytokine-mediated signaling pathway GO:0002237 response to molecule of bacterial origin GO:0007159 leukocyte cell-cell adhesion GO:0007259 JAK-STAT cascade GO:0009306 protein secretion GO:0009615 response to virus GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0032479 regulation of type I interferon production GO:0032481 positive regulation of type I interferon production GO:0032496 response to lipopolysaccharide GO:0032606 type I interferon production GO:0032608 interferon-beta production GO:0032609 interferon-gamma production GO:0032611 interleukin-1 beta production GO:0032612 interleukin-1 production GO:0032648 regulation of interferon-beta production GO:0032649 regulation of interferon-gamma production GO:0032651 regulation of interleukin-1 beta production GO:0032652 regulation of interleukin-1 production GO:0032728 positive regulation of interferon-beta production GO:0032729 positive regulation of interferon-gamma production GO:0032731 positive regulation of interleukin-1 beta production GO:0032732 positive regulation of interleukin-1 production GO:0034340 response to type I interferon GO:0035455 response to interferon-alpha GO:0035457 cellular response to interferon-alpha GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0042110 T cell activation GO:0045088 regulation of innate immune response GO:0045351 type I interferon biosynthetic process GO:0050663 cytokine secretion GO:0050701 interleukin-1 secretion GO:0050702 interleukin-1 beta secretion GO:0050704 regulation of interleukin-1 secretion GO:0050706 regulation of interleukin-1 beta secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050715 positive regulation of cytokine secretion GO:0050716 positive regulation of interleukin-1 secretion GO:0050718 positive regulation of interleukin-1 beta secretion GO:0050730 regulation of peptidyl-tyrosine phosphorylation GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0051607 defense response to virus GO:0060337 type I interferon signaling pathway GO:0060338 regulation of type I interferon-mediated signaling pathway GO:0060759 regulation of response to cytokine stimulus GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071357 cellular response to type I interferon GO:0071593 lymphocyte aggregation GO:0097696 STAT cascade GO:0098542 defense response to other organism GO:1903532 positive regulation of secretion by cell GO:1904951 positive regulation of establishment of protein localization
Molecular Function	GO:0004896 cytokine receptor activity GO:0004904 interferon receptor activity GO:0004905 type I interferon receptor activity GO:0019955 cytokine binding GO:0019961 interferon binding GO:0019962 type I interferon binding
Cellular Component	GO:0005770 late endosome

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04151 PI3K-Akt signaling pathway hsa04380 Osteoclast differentiation hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-like receptor signaling pathway hsa04630 Jak-STAT signaling pathway hsa04650 Natural killer cell mediated cytotoxicity
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-913531: Interferon Signaling R-HSA-909733: Interferon alpha/beta signaling R-HSA-912694: Regulation of IFNA signaling

Summary
Symbol	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IFNAR1 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 IFNAR1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28196594	Colorectal Carcinoma	Promote immunity	Genetic stabilization of IFNAR1 improved CTL survival and increased the efficacy of the chimeric antigen receptor T cell transfer and PD-1 inhibition.
28723893	Melanoma	Promote immunity; increase the efficacy of immunotherapy	We confirmed this finding in an in vivo competitive assay that compared the relative growth of mixtures of isogenic Stat1-null or control B16 cells in animals treated with immunotherapy (Fig. 1f). In wild-type mice treated with GVAX and anti-PD-1 immunotherapy, the relative proportion of Stat1-null cells increased significantly (Fig. 1g, h; P < 0.01, Student’s t-test), suggesting that Stat1-null cells have a marked growth advantage over wild-type tumour cells when under immune attack. Similar results were obtained for Jak1-null and Ifngr1-null cells (Fig. 1h).
29622580	breast carcinoma	Promote immunity	IFNAR-neuT tumors exhibited deregulation of genes having adverse prognostic value in breast cancer patients, including the breast cancer stem cell (BCSC) marker aldehyde dehydrogenase-1A1 (ALDH1A1).
20233880	Prostate Carcinoma	Promote immunity	Like TLR3(-/-) mice, IFN-alpha receptor 1 (IFNAR1)(-/-) mice exhibited reduced tumor surveillance and impaired tumor suppression following polyI:C treatment.
21930769	Fibrosarcoma	Promote immunity	We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre(+)Ifnar1(f/f) mice) cannot reject highly immunogenic tumor cells and that CD8α(+) DCs from these mice display defects in antigen cross-presentation to CD8(+) T cells

Summary
Symbol	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
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 IFNAR1 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	logFC: 1.42; FDR: 0.000150	Sensitive to T cell-mediated killing
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	STARS Score: 9.02; FDR: 0.000	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 7.37; FDR: 0.000	Sensitive to T cell-mediated killing
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	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
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 IFNAR1 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	0.136	0.664
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.097	0.957
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.166	0.9
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.115	0.745
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.096	0.954
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.39	0.864
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.01	0.982
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.002	0.999
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.031	0.988
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.202	0.889
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	1.032	0.625
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.088	0.192

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IFNAR1 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	11.1	0	11.1	0.36
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	25	0	25	0.364
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	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IFNAR1. 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	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IFNAR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IFNAR1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IFNAR1. 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	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IFNAR1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IFNAR1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IFNAR1
Name	interferon (alpha, beta and omega) receptor 1
Aliases	IFRC; IFNAR; IFNBR; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; alpha-type antiviral protein; beta-type anti ......
Chromosomal Location	21q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IFNAR1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IFNAR1.

ID	Name	Drug Type	Targets	#Targets
DB00008	Peginterferon alfa-2a	Biotech	IFNAR1, IFNAR2	2
DB00011	Interferon alfa-n1	Biotech	IFNAR1, IFNAR2	2
DB00018	Interferon alfa-n3	Biotech	IFNAR1, IFNAR2	2
DB00022	Peginterferon alfa-2b	Biotech	IFNAR1, IFNAR2	2
DB00034	Interferon Alfa-2a, Recombinant	Biotech	IFNAR1, IFNAR2	2
DB00060	Interferon beta-1a	Biotech	IFNAR1, IFNAR2	2
DB00068	Interferon beta-1b	Biotech	IFNAR1, IFNAR2	2
DB00069	Interferon alfacon-1	Biotech	IFNAR1, IFNAR2	2
DB00105	Interferon Alfa-2b, Recombinant	Biotech	IFNAR1, IFNAR2	2
DB05258	Natural alpha interferon	Biotech	IFNAR1	1
DB05472	omega interferon	Small Molecule	IFNAR1, IFNAR2	2

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