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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
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CYBB Louise Daugherty commented on gene: CYBB: Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CYBB Louise Daugherty edited their review of gene: CYBB: Added comment: Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.; Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CYBB Kimberly Gilmour reviewed gene: CYBB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CYBB Tracy Briggs reviewed gene: CYBB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v1.60 CYBB Louise Daugherty Source NHS GMS was added to CYBB.
Primary immunodeficiency or monogenic inflammatory bowel disease v1.59 CYBB Louise Daugherty Source North West GLH was added to CYBB.
Primary immunodeficiency or monogenic inflammatory bowel disease v1.58 CYBB Louise Daugherty Source London North GLH was added to CYBB.
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty commented on gene: CYBB
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty classified CYBB as Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty marked gene: CYBB as ready
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty classified CYBB as Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Sophie Hambleton reviewed gene: CYBB
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Ellen McDonagh commented on CYBB
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty commented on CYBB
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty commented on CYBB
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty commented on CYBB
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty reviewed CYBB
Primary immunodeficiency or monogenic inflammatory bowel disease CYBB Louise Daugherty Added gene to panel