• Gene: IFIH1 (Interferon Induced with Helicase C Domain 1, also known as MDA5)

• Chromosome: 2q24.2

• Position (GRCh38): Chr2: 163125420

• Location Within Gene: Exon 15 (missense variant)

• T allele

• Encodes an amino acid substitution: Alanine to Threonine at position 946 (A946T)
  
  

• The T allele leads to a gain-of-function mutation in the MDA5 protein

• Results in increased basal interferon signaling, even in the absence of viral RNA

• Elevates expression of interferon-stimulated genes (ISGs)

• MDA5 is a cytosolic pattern recognition receptor (PRR) that detects viral double-stranded RNA

• Hyperactive variants like T946 increase chronic Type I IFN response

• Triggers persistent low-grade inflammation, even in sterile (non-infectious) environments
  
  

• European (EUR): T allele ~35–40%

• East Asian (EAS): T allele ~10–15%

• African (AFR): T allele ~20–25%
  (Source: gnomAD, 1000 Genomes)

• IFIH1, MAVS, IRF3, STAT1, IFNB1

• Type I interferon signaling

• Innate antiviral response

• PRR (pattern recognition receptor) pathways

• JAK-STAT downstream effectors

• Autoimmune Addison’s Disease

• Type 1 Diabetes

• Systemic Lupus Erythematosus

• Psoriasis

• Graves’ Disease

• Vitiligo

• Aicardi–Goutières syndrome (rare monogenic IFN disorder)

• rs1990760 has been implicated in overactive interferon responses seen in multiple autoimmune diseases

• Mice carrying similar IFIH1 variants develop IFN-driven pathology even without infection

• Variant carriers exhibit increased expression of ISGs in blood and affected tissues

• T allele carriers may have a “primed” innate immune system, ready to overreact to minor stimuli

• This may predispose to autoimmune flare-ups following viral infections

• A key marker for interferon-targeted therapies

rs1990760 is a functional SNP in IFIH1 that leads to a hyperresponsive innate immune system. By amplifying the interferon alarm system, it contributes to the development of Addison’s and other autoimmune diseases—especially those triggered or worsened by viral infections.

ItemThis SNP report is intended for informational and educational purposes only. It should not be used to diagnose or treat any health condition. All genetic findings must be interpreted by qualified medical professionals in the context of clinical and family history. description