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| Primary immunodeficiency or monogenic inflammatory bowel disease v9.9 | NOX1 |
Boaz Palterer gene: NOX1 was added gene: NOX1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: NOX1 were set to 32064493; 26301257; 29091079 Phenotypes for gene: NOX1 were set to Inflammatory bowel disease; IBD; VEOIBD Penetrance for gene: NOX1 were set to unknown Review for gene: NOX1 was set to RED Added comment: NOX1 is an X-linked gene encoding NADPH Oxidase 1, an enzyme highly expressed in the colonic epithelium. At the apical brush border, NOX1 constitutively generates reactive oxygen species (ROS) into the crypt lumen. This localized ROS production is a critical component of the intestinal epithelial barrier, mediating innate antimicrobial defense and regulating host-microbe interactions at the mucosal interface without playing a role in systemic phagocytic oxidative bursts. Defects in NOX1 are associated with mucosal immune dysregulation and Very Early-Onset Inflammatory Bowel Disease (VEO-IBD). Hemizygous loss-of-function missense variants (e.g., p.N122H) have been identified in male patients presenting with severe, early-onset ulcerative colitis-like pathology and pancolitis. Functional analyses of patient-derived organoids and ex vivo colonic explants demonstrate that these variants profoundly abrogate epithelial ROS production, leading to impaired host resistance to enteric microbes and subsequent severe intestinal inflammation (Hayes et al., 2015; Schwerd et al., 2018). Unlike defects in the phagocytic NADPH oxidase (CYBB/NOX2), which cause classical Chronic Granulomatous Disease with systemic susceptibility to infection, NOX1 deficiency specifically impairs the epithelial innate immune compartment. Furthermore, large cohort analyses suggest that NOX1 loss-of-function variants may not always present as a fully penetrant Mendelian disorder, but rather act as a high-impact genetic modifier that drastically lowers the threshold for VEO-IBD when combined with specific microbial or environmental triggers (Schwerd et al., 2018). Sources: Literature |
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