Furthermore, in the case of very early onset IBD, the ROS-induced NOD2 activation via the p22phox-NOD2 interaction was abrogated by loss-of-function variants in the NADPH oxidase complex, which confirmed that missense variants in NOX1 and p22phox are functionally linked to NOD2 [49]. The gene discussed is FMO5; the disease is inflammatory bowel disease.