The ISR induces phosphorylation of eukaryotic initiation factor subunit alpha (eIF2α), and activation of the Atf4 axis, through four upstream kinases; HRI (eIF2α kinase heme‐regulated inhibitor), GCN2 (general control nonderepressible 2), PKR (double‐stranded RNA [dsRNA]‐dependent protein kinase) and PERK, in response to hypoxia, nutrient deprivation, viral infection, and oxidative stress, respectively (Wek et al., 2006). The gene discussed is EIF2AK4; the disease is viral infectious disease.