Similar epistatic regulation was documented in ALPS patients with variants of both FAS and PRF1 (99) or FAS and CASP10 (100), patients with hyperimmunoglobulinemia D and periodic fever syndrome with MVK and TNFRSF1A variants (101), patients with broad susceptibility to infections associated with IFNAR1 and IFNGR2 variants (102), patients with X-linked immunodeficiency caused by XIAP variant and a CD40LG polymorphism (103), and pediatric patients with inflammatory bowel disease, in which a known NOD2 variant probably interacts with variants of GSDMB, ERAP2, or SEC16A (104). The gene discussed is FAS; the disease is inflammatory bowel disease.