rs3747517

This is a variant in the IFIH1 gene that changes a histidine to an arginine.

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GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

psoriasis

Yin X et al. “Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.” Nature Communications 6:6916 (2015)
Allele T
OR 1.30
p 1.0e-18
N 13,816
Meta-analysisLarge GWAS
multi-ancestry

anti-NMDA receptor encephalitis

Liu X et al. “Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.” Neurology(r) Neuroimmunology & Neuroinflammation 11(3):e200221 (2024)
Allele C
OR 1.55
p 1.0e-8
N 6,954
Large GWAS
East Asian
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ClinVar annotation

Benign★★★☆
10 submitters2 publications

Aicardi-Goutieres syndrome 7 (AGS7); Singleton-Merten syndrome 1 (SGMRT1); not specified

View on ClinVar →
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Research that mentions this SNP (2)

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Replication of the association between the C8orf13–BLK region and systemic lupus erythematosus in a Japanese population
ReviewIkue Ito et al.(2009)· Arthritis &amp; Rheumatism

This comprehensive review examines genetic associations in type I interferon-related signaling pathways across multiple autoimmune diseases. The authors review evidence linking dysregulated interferon alpha (IFNα) signaling to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune conditions, identifying multiple susceptibility genes including IFIH1, IRF5, STAT4, TYK2, BLK, BANK1, FCGR2A, and TREX1 with well-replicated associations and functional relevance to IFN pathway dysfunction.

Traits studied:Autoimmune Thyroid DiseaseCrohn's DiseaseDermatomyositisGiant Cell ArteritisGraves' DiseaseInflammatory Bowel DiseaseJuvenile Idiopathic ArthritisLupus NephritisMicroscopic PolyangiitisMultiple SclerosisPrimary Anti-Phospholipid SyndromePrimary Sjögren's SyndromePsoriasisRheumatoid ArthritisSclerodermaSystemic Lupus ErythematosusType 1 DiabetesUlcerative ColitisWegener's Granulomatosis
PubMedDOIMetascience Observatory
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The association between the IFIH1 locus and type 1 diabetes
AssociationN=1,767Qu HQ et al.(2008)· Diabetologia

This study validates the association between IFIH1 gene variants and type 1 diabetes in an independent cohort of 589 family trios (1,767 individuals) of mixed European descent. Using family-based association testing, the authors confirmed significant associations for rs2111485 (OR=0.84, p=0.0244) and rs984971 (OR=0.85, p=0.0455), replicating the previously reported IFIH1 locus findings. The results support the role of innate antivirus immunity in type 1 diabetes pathogenesis.

Traits studied:Type 1 diabetes
PubMedDOIMetascience Observatory

About IFIH1

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]

View all IFIH1 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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