rs35667974

This is a variant in the IFIH1 gene that changes a isoleucine to an valine.

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GWAS Catalog Trait Associations (6)

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

interferon lambda-1 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 0.32
p 9.0e-53
N 47,745
Large GWAS
European

hypothyroidism

White SL et al. “Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.” Nature Genetics 58(2):307-316 (2026)
Allele C
OR 0.18
p 1.0e-38
N 2,444,128
Large GWAS
multi-ancestry
Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 0.28
p 3.0e-14
N 394,626
Large GWAS
European

lymphocyte count

Chen MH et al. “Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.” Cell 182(5):1198-1213.e14 (2020)
Allele C
OR —
p 4.0e-15
N 643,370
Large GWAS
multi-ancestry

X-12127 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.25
p 6.0e-13
N 14,296
Large GWAS
European

autoimmune thyroid disease

Saevarsdottir S et al. “FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease.” Nature 584(7822):619-623 (2020)
Allele T
OR 1.27
p 9.0e-13
N 754,406
Large GWAS
European

type 1 diabetes mellitus

Onengut-Gumuscu S et al. “Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.” Nature Genetics 47(4):381-6 (2015)
Allele T
OR 1.69
p 9.0e-9
N 21,526
Large GWAS
European
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ClinVar annotation

Likely Benign★★★☆
7 submitters2 publications

Aicardi-Goutieres syndrome 7 (AGS7); IFIH1-related disorder; Singleton-Merten syndrome 1 (SGMRT1); not specified

View on ClinVar →
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Research that mentions this SNP (1)

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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

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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