CYBB

The CYBB gene encodes the β-subunit of cytochrome b-245 (commonly known as gp91phox), a critical component of the phagocyte NADPH oxidase complex. This transmembrane protein, also designated NOX2, facilitates superoxide generation by transferring electrons from cytosolic NADPH to molecular oxygen during the "respiratory burst" in innate immunity. Functionally, it partners with p22phox to form flavocytochrome b558, which interacts with regulatory subunits (p47phox, p67phox, p40phox, and Rac) upon phagocyte activation. CYBB-mediated reactive oxygen species (ROS) production is essential for microbial killing through the NOX2/ROS signaling axis, intersecting with inflammatory pathways like NF-κB and NLRP3 inflammasome activation. Mutations in CYBB cause X-linked chronic granulomatous disease (X-CGD), characterized by recurrent bacterial/fungal infections and granuloma formation. Current therapeutic strategies include interferon-γ immunotherapy and hematopoietic stem cell transplantation, with emerging lentiviral gene therapy trials (NCT01855685, NCT02757911) demonstrating preliminary efficacy in restoring NADPH oxidase function.