IFIH1 interferon induced with helicase C domain 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IFIH1provided by HGNC
Official Full Name: interferon induced with helicase C domain 1provided by HGNC
Primary source: HGNC:HGNC:18873
See related: Ensembl:ENSG00000115267 MIM:606951; AllianceGenome:HGNC:18873
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AGS7; Hlcd; MDA5; IMD95; MDA-5; RLR-2; IDDM19; SGMRT1
Summary: IFIH1 encodes MDA5 which is an intracellular sensor of viral RNA that triggers the innate immune response. Sensing RNA length and secondary structure, MDA5 binds dsRNA oligonucleotides with a modified DExD/H-box helicase core and a C-terminal domain, thus leading to a proinflammatory response that includes interferons. It has been shown that Coronaviruses (CoVs) as well as various other virus families, are capable of evading the MDA5-dependent interferon response, thus impeding the activation of the innate immune response to infection. MDA5 has also been shown to play an important role in enhancing natural killer cell function in malaria infection. In addition to its protective role in antiviral responses, MDA5 has been implicated in autoimmune and autoinflammatory diseases such as type 1 diabetes, systemic lupus erythematosus, and Aicardi-Goutieres syndrome[provided by RefSeq, Jul 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression: Ubiquitous expression in spleen (RPKM 10.9), appendix (RPKM 9.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q24.2

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (162267074..162318684, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (162723727..162775351, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (163123584..163175194, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Temporal regulation of MDA5 inactivation by Caspase-3 dependent cleavage of 14-3-3eta.
Title: Temporal regulation of MDA5 inactivation by Caspase-3 dependent cleavage of 14-3-3η.
IBR1, a novel endogenous IFIH1-binding dsRNA, governs IFIH1 activation and M1 macrophage polarisation in ARDS.
Title: IBR1, a novel endogenous IFIH1-binding dsRNA, governs IFIH1 activation and M1 macrophage polarisation in ARDS.
IFIH1 variants are associated with generalised epilepsy preceded by febrile seizures.
Title: IFIH1 variants are associated with generalised epilepsy preceded by febrile seizures.
Identifying the association between polymorphisms in the GZMB and IFIH1 genes and psoriasis in Egyptians.
Title: Identifying the association between polymorphisms in the GZMB and IFIH1 genes and psoriasis in Egyptians.
IFIH1 (MDA5) is required for innate immune detection of intron-containing RNA expressed from the HIV-1 provirus.
Title: IFIH1 (MDA5) is required for innate immune detection of intron-containing RNA expressed from the HIV-1 provirus.
Mammalian reovirus micro1 protein attenuates RIG-I and MDA5-mediated signaling transduction by blocking IRF3 phosphorylation and nuclear translocation.
Title: Mammalian reovirus µ1 protein attenuates RIG-I and MDA5-mediated signaling transduction by blocking IRF3 phosphorylation and nuclear translocation.
Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.
Title: Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.
Contrasting functions of ATP hydrolysis by MDA5 and LGP2 in viral RNA sensing.
Title: Contrasting functions of ATP hydrolysis by MDA5 and LGP2 in viral RNA sensing.
Hepatitis C virus NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes.
Title: Hepatitis C virus NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes.
Global trends in research of melanoma differentiation-associated gene 5: a bibliometric analysis from 2002 to 2022.
Title: Global trends in research of melanoma differentiation-associated gene 5: a bibliometric analysis from 2002 to 2022.

Submit: New GeneRIF Correction See all GeneRIFs (267)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Aicardi-Goutieres syndrome 7 MedGen: C3888244 OMIM: 615846 GeneReviews: Aicardi-Goutieres Syndrome	not available
Immunodeficiency 95 MedGen: C5676929 OMIM: 619773 GeneReviews: Not available	not available
Singleton-Merten syndrome 1 MedGen: C4225427 OMIM: 182250 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. EBI GWAS Catalog EBI GWAS CatalogPubMed
Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	HIV-1 Vpr upregulates the gene expression of IFIH1 in human monocyte-derived dendritic cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP-dependent H2AZ histone chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent H3-H4 histone complex chaperone activity	IEA Inferred from Electronic Annotation more info
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA clamp loader activity	IEA Inferred from Electronic Annotation more info
enables RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA helicase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables chromatin extrusion motor activity	IEA Inferred from Electronic Annotation more info
enables cohesin loader activity	IEA Inferred from Electronic Annotation more info
enables double-stranded RNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables double-stranded RNA binding	TAS Traceable Author Statement more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables pattern recognition receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ribonucleoprotein complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded RNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables single-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in MDA-5 signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in MDA-5 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in MDA-5 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in antiviral innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to exogenous dsRNA	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to virus	IEP Inferred from Expression Pattern more info	PubMed
involved_in chromatin looping	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in cytoplasmic pattern recognition receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in detection of virus	TAS Traceable Author Statement more info	PubMed
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of viral genome replication	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-alpha production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interferon-alpha production	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of interferon-beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-beta production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interferon-beta production	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of response to cytokine stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein complex oligomerization	IEA Inferred from Electronic Annotation more info
involved_in protein sumoylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of type III interferon production	TAS Traceable Author Statement more info	PubMed
involved_in response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	TAS Traceable Author Statement more info	PubMed
involved_in type I interferon-mediated signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: interferon-induced helicase C domain-containing protein 1

Names: CADM-140 autoantigen; DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide; RIG-I-like receptor 2; RNA helicase-DEAD box protein 116; clinically amyopathic dermatomyositis autoantigen 140 kDa; helicard; helicase with 2 CARD domains; melanoma differentiation-associated gene 5; melanoma differentiation-associated protein 5; murabutide down-regulated protein

NP_071451.2

EC 3.6.4.13

XP_047301363.1

EC 3.6.4.13

XP_054199313.1

EC 3.6.4.13

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011495.1 RefSeqGene

Range

4846..56456

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1235

mRNA and Protein(s)

NM_022168.4 → NP_071451.2 interferon-induced helicase C domain-containing protein 1

See identical proteins and their annotated locations for NP_071451.2

Status: REVIEWED

Source sequence(s)

AC007750, AF095844, BC046208, BC111750

Consensus CDS

CCDS2217.1

UniProtKB/Swiss-Prot

Q2NKL6, Q6DC96, Q86X56, Q96MX8, Q9BYX4, Q9H3G6

UniProtKB/TrEMBL

A8KA76

Related

ENSP00000497271.1, ENST00000649979.2

Conserved Domains (7) summary

COG1111
Location:306 → 873

MPH1; ERCC4-related helicase [Replication, recombination and repair]

cd08818
Location:8 → 99

CARD_MDA5_r1; Caspase activation and recruitment domain found in MDA5, first repeat

cd08819
Location:111 → 201

CARD_MDA5_r2; Caspase activation and recruitment domain found in MDA5, second repeat

cd15807
Location:900 → 1015

MDA5_C; C-terminal domain of Melanoma differentiation-associated protein 5, a cytoplasmic viral RNA receptor

cd12090
Location:548 → 694

MDA5_ID; Insert domain of MDA5

pfam00271
Location:698 → 823

Helicase_C; Helicase conserved C-terminal domain

pfam04851
Location:305 → 491

ResIII; Type III restriction enzyme, res subunit