Browse IFIH1

Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
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
 
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
 
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
 
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
SymbolIFIH1
Nameinterferon 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 Location2q24.2
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
 
  Literatures describing the relation between IFIH1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25012502Pancreatic ductal adenocarcinomaPromote immunity (T cell function); increase the efficacy of immunotherapyIn addition, MDA5-based immunotherapy led to effective tumor control of established pancreatic tumors.
21728171Ovarian CarcinomaPromote immunityMonocytes 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
SymbolIFIH1
Nameinterferon 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 Location2q24.2
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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0250.941
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4230.767
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3450.719
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1020.778
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.4990.755
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4030.848
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3720.466
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.8940.555
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2210.897
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9920.435
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9190.639
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0550.671
> Mutation difference between responders and non-responders
 
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 Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.42.74.70.294
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.43.440.587
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
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
 
Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
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
 
> Receptor
 
Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IFIH1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IFIH1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIFIH1
Nameinterferon 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 Location2q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IFIH1 collected from DrugBank database.
> Drugs from DrugBank database
 

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