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Gene Review

IFIH1  -  interferon induced with helicase C domain 1

Homo sapiens

Synonyms: AGS7, CADM-140 autoantigen, Clinically amyopathic dermatomyositis autoantigen 140 kDa, Helicard, Helicase with 2 CARD domains, ...
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Disease relevance of IFIH1


High impact information on IFIH1

  • In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24 [5].
  • A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region [5].
  • Induction of type I interferons (IFNs) by viruses and other pathogens is crucial for innate immunity, and it is mediated by the activation of pattern-recognition receptors, such as Toll-like receptors and cytosolic receptors such as RIG-I and MDA5 [6].
  • RNA binding studies and analysis of cells lacking RIG-I, or the related MDA5 protein, demonstrated that RIG-I, but not MDA5, efficiently binds to secondary structured HCV RNA to confer induction of IFN-beta expression [7].
  • Atypical helicase motifs of MDA-5 deviate from consensus sequences but are well conserved in a potentially new group of cloned and hypothetical proteins. mda-5 is an early response gene inducible by IFN and tumor necrosis factor-alpha, responding predominantly to IFN-beta [1].

Biological context of IFIH1


Anatomical context of IFIH1

  • RIG-I/MDA5 recognizes dsRNA in the cytoplasm, whereas TLR3 resides in the cell surface membrane or endosomes to engage in extracytoplasmic recognition of dsRNA [10].
  • This study tested the hypothesis that RSAD2 and IFIH1 were induced in the endometrium in a cell type-specific manner by IFNT from the conceptus during early pregnancy [9].
  • Pregnancy and interferon tau regulate RSAD2 and IFIH1 expression in the ovine uterus [9].
  • In pregnant ewes, RSAD2 and IFIH1 mRNAs increased in endometrial glands, and stroma and immune cells, but not in the luminal epithelium [9].
  • Infections with RNA viruses are sensed by the innate immune system through membrane-bound Toll-like receptors or the cytoplasmic RNA helicases RIG-I and MDA-5 [4].

Associations of IFIH1 with chemical compounds

  • These results indicate that conceptus IFNT induces both RSAD2 and IFIH1 in a P4-independent manner in the ovine uterine endometrium [9].
  • The MDA-5 cleavage product observed in cells treated with puromycin is approximately 90 kDa, similar in size to the putative cleavage product observed in poliovirus-infected cells [4].

Other interactions of IFIH1


  1. mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Kang, D.C., Gopalkrishnan, R.V., Wu, Q., Jankowsky, E., Pyle, A.M., Fisher, P.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication. Cocude, C., Truong, M.J., Billaut-Mulot, O., Delsart, V., Darcissac, E., Capron, A., Mouton, Y., Bahr, G.M. J. Gen. Virol. (2003) [Pubmed]
  3. IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Opitz, B., Rejaibi, A., Dauber, B., Eckhard, J., Vinzing, M., Schmeck, B., Hippenstiel, S., Suttorp, N., Wolff, T. Cell. Microbiol. (2007) [Pubmed]
  4. MDA-5 Is Cleaved in Poliovirus-Infected Cells. Barral, P.M., Morrison, J.M., Drahos, J., Gupta, P., Sarkar, D., Fisher, P.B., Racaniello, V.R. J. Virol. (2007) [Pubmed]
  5. A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Smyth, D.J., Cooper, J.D., Bailey, R., Field, S., Burren, O., Smink, L.J., Guja, C., Ionescu-Tirgoviste, C., Widmer, B., Dunger, D.B., Savage, D.A., Walker, N.M., Clayton, D.G., Todd, J.A. Nat. Genet. (2006) [Pubmed]
  6. Type I inteferon gene induction by the interferon regulatory factor family of transcription factors. Honda, K., Takaoka, A., Taniguchi, T. Immunity (2006) [Pubmed]
  7. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Saito, T., Hirai, R., Loo, Y.M., Owen, D., Johnson, C.L., Sinha, S.C., Akira, S., Fujita, T., Gale, M. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  8. Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation. Kovacsovics, M., Martinon, F., Micheau, O., Bodmer, J.L., Hofmann, K., Tschopp, J. Curr. Biol. (2002) [Pubmed]
  9. Pregnancy and interferon tau regulate RSAD2 and IFIH1 expression in the ovine uterus. Song, G., Bazer, F.W., Spencer, T.E. Reproduction (2007) [Pubmed]
  10. NAK-Associated Protein 1 Participates in Both the TLR3 and the Cytoplasmic Pathways in Type I IFN Induction. Sasai, M., Shingai, M., Funami, K., Yoneyama, M., Fujita, T., Matsumoto, M., Seya, T. J. Immunol. (2006) [Pubmed]
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