In SLE, multiple variants in the IFIH1 gene (p.Gly821Ser, p.Ala946Thr, and p.Arg779His) have been identified (Van Eyck et al., 2015), and recombinant MDA5 variants G821S and A946T exhibit the altered conformations compared to the wild-type, potentially activating downstream signaling in the absence of RNA (Funabiki et al., 2014). Here, IFIH1 is linked to systemic lupus erythematosus.