Cytochrome b-245 beta chain (gp91-phox) (CYBB)

The Cytochrome b-245 beta chain, also known as gp91-phox or NOX2, is the catalytic subunit of the phagocyte NADPH oxidase (phox) enzyme complex and is encoded by the CYBB gene [6, 10, 15]. It is a transmembrane glycoprotein that functions as an oxidoreductase, transferring electrons across the phagosomal membrane to molecular oxygen to produce superoxide radicals during the 'respiratory burst' [7, 10]. This process is essential for the microbicidal activity of neutrophils, monocytes, and macrophages, enabling the innate immune system to destroy invading bacteria and fungi [10, 18]. Mutations in the CYBB gene are the most common cause of X-linked chronic granulomatous disease (X-CGD), a severe primary immunodeficiency characterized by life-threatening recurrent infections and chronic inflammatory complications [4, 11, 14]. Clinically, CYBB is a primary target for curative gene therapies such as EN-374 and MyeloVec, which aim to restore functional oxidase activity in hematopoietic stem cells [1, 2, 4, 5]. Furthermore, because excessive NOX2-derived reactive oxygen species contribute to tissue damage in chronic inflammatory, cardiovascular, and neurodegenerative disorders, inhibitors of this target are being explored as potential therapeutics to mitigate pathological oxidative stress [7, 15, 19].

Other names

Cytochrome b-245 heavy chainNOX2Cytochrome b558 subunit betaNADPH oxidase 2p91-PHOXgp91phoxSuperoxide-generating NADPH oxidase heavy chain subunitNeutrophil cytochrome b 91 kDa polypeptide

Restoration of protein function via gene therapy, upregulation of residual oxidase activity, or targeted enzyme inhibition to reduce oxidative stress