TISIDB

Summary
Symbol	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
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	Cytoplasm Nucleus Note=May be found in the nucleus, during apoptosis.
Domain	PF16739 Caspase recruitment domain PF00271 Helicase conserved C-terminal domain PF04851 Type III restriction enzyme PF11648 C-terminal domain of RIG-I
Function	Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV) and mengo encephalomyocarditis virus (ENMG). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.

> Gene Ontology [ TOP ]
Biological Process	GO:0001818 negative regulation of cytokine production GO:0001819 positive regulation of cytokine production GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002753 cytoplasmic pattern recognition receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0009597 detection of virus GO:0009615 response to virus GO:0016925 protein sumoylation GO:0018205 peptidyl-lysine modification GO:0030522 intracellular receptor signaling pathway GO:0031349 positive regulation of defense response GO:0032479 regulation of type I interferon production GO:0032480 negative regulation of type I interferon production GO:0032481 positive regulation of type I interferon production GO:0032606 type I interferon production GO:0032607 interferon-alpha production GO:0032608 interferon-beta production GO:0032647 regulation of interferon-alpha production GO:0032648 regulation of interferon-beta production GO:0032727 positive regulation of interferon-alpha production GO:0032728 positive regulation of interferon-beta production GO:0034343 type III interferon production GO:0034344 regulation of type III interferon production GO:0039528 cytoplasmic pattern recognition receptor signaling pathway in response to virus GO:0039530 MDA-5 signaling pathway GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0051607 defense response to virus GO:0098542 defense response to other organism GO:0098586 cellular response to virus
Molecular Function	GO:0003725 double-stranded RNA binding GO:0003727 single-stranded RNA binding GO:0004386 helicase activity GO:0043021 ribonucleoprotein complex binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04622 RIG-I-like receptor signaling pathway
Reactome	R-HSA-5688426: Deubiquitination R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-392499: Metabolism of proteins R-HSA-933543: NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 R-HSA-936440: Negative regulators of RIG-I/MDA5 signaling R-HSA-5689896: Ovarian tumor domain proteases R-HSA-597592: Post-translational protein modification R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways R-HSA-918233: TRAF3-dependent IRF activation pathway R-HSA-933541: TRAF6 mediated IRF7 activation R-HSA-933542: TRAF6 mediated NF-kB activation R-HSA-5689880: Ub-specific processing proteases

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04622 RIG-I-like receptor signaling pathway

Reactome

R-HSA-5688426: Deubiquitination
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-933543: NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-936440: Negative regulators of RIG-I/MDA5 signaling
R-HSA-5689896: Ovarian tumor domain proteases
R-HSA-597592: Post-translational protein modification
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-918233: TRAF3-dependent IRF activation pathway
R-HSA-933541: TRAF6 mediated IRF7 activation
R-HSA-933542: TRAF6 mediated NF-kB activation
R-HSA-5689880: Ub-specific processing proteases

Summary
Symbol	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IFIH1 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 IFIH1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25012502	Pancreatic ductal adenocarcinoma	Promote immunity (T cell function); increase the efficacy of immunotherapy	In addition, MDA5-based immunotherapy led to effective tumor control of established pancreatic tumors.
21728171	Ovarian Carcinoma	Promote immunity	Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells, and subsequently upregulated HLA-class I/II and costimulatory molecules, and secreted CXCL10 and IFN-α. Further, this proinflammatory milieu promoted cytolytic activity and IFN-γ secretion of NK cells. Thus, our data suggest that the engagement of MDA-5 in a whole tumor cell vaccine is a promising approach for the immunotherapy of ovarian cancer.

Summary
Symbol	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
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 IFIH1 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	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
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 IFIH1 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	-0.025	0.941
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.423	0.767
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.345	0.719
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.102	0.778
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.499	0.755
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.403	0.848
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.372	0.466
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.894	0.555
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.221	0.897
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.992	0.435
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	0.919	0.639
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.055	0.671

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IFIH1 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	7.4	2.7	4.7	0.294
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	7.4	3.4	4	0.587
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	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	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
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	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IFIH1. 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	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IFIH1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IFIH1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IFIH1. 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	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IFIH1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IFIH1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IFIH1
Name	interferon induced with helicase C domain 1
Aliases	MDA-5; Hlcd; MDA5; IDDM19; helicard; AGS7; RLR-2; SGMRT1; CADM-140 autoantigen; RIG-I-like receptor 2; RNA h ......
Chromosomal Location	2q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IFIH1 collected from DrugBank database.

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

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