Alt. symbols: MDA-5 | Hlcd | MDA5 | IDDM19

Approved name: interferon induced with helicase C domain 1
Alt. names: helicard, melanoma differentiation-associated gene 5

Location: 2q24.2: 162267074 - 162318684 (-)
Gene type: protein_coding, 8 transcripts.

Scores: LoFtool: 0.992000 | pLI: 0.00000000 | LOEUF: 1.548

HGNC: 18873

NCBI: 64135, RefSeq: NG_011495.1

Ensembl: ENSG00000115267.10

LRG_1235 | Status: public

OMIM: 606951

Expression | ProteinAtlas

IFIH1 encodes MDA5, an innate immune receptor that acts as a cytoplasmic sensor of viral nucleic acids and activates type I interferon (IFN) signaling through the MAVS adaptor molecule. Therefore, it plays a major role in sensing viral infection and in the activation cascade of antiviral responses, including the induction of type I IFNs and pro-inflammatory cytokines.

Monoallelic IFIH1 missense gain-of-function (GOF) mutations are associated with a primary type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi-Goutieres syndrome (AGS) 7 [MIM:615846] and Singleton-Merten syndrome (SMS) 1 [MIM:182250]. Though both involve systemic type I IFN activation, AGS patients tend to present with more severe neurological features, while SGS patients are typical affected by issues involving their vasculature, teeth, eyes, bone and joints. IFIH1 GOF mutations can also be associated with the development of autoimmunity, most prominently a lupus-like illness involving dysgammaglobulinemia, autoantibody production, and cytopenias (PMID: 31898846). SNPs in IFIH1 have also been linked to a variety of autoimmune disorders including systemic lupus erythematosus (SLE) in GWAS and other studies (PMID: 29930297, 21705624). In contrast, mono- and bi-allelic IFIH1 loss-of-function (LOF) variants have been implicated in the development of VEO-IBD (PMID: 34185153), as well as susceptibility to common respiratory viral infections (PMID: 28716935) and protection against the development of type 1 diabetes (PMID: 19264985, 20844740). [Load More]