CYBA encoding p22phox, the cytochrome b558 alpha polypeptide: gene structure, expression, role and physiopathology

• P22phox is a ubiquitous protein encoded by the CYBA gene located on chromosome 16.
• P22phox is a critical component of the superoxide-generating NADPH oxidases.
• Mutations in CYBA lead to the rare form of chronic granulomatous disease AR220CGD.
• P22phox-deficient mice suffer from vestibular dysfunction.
• Polymorphisms in CYBA seem to be associated with coronary artery and heart diseases.

P22phox is a ubiquitous protein encoded by the CYBA gene located on the long arm of chromosome 16 at position 24, containing six exons and spanning 8.5 kb. P22phox is a critical component of the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). It is associated with NOX2 to form cytochrome b558 expressed mainly in phagocytes and responsible for the killing of microorganisms when bacterial and fungal infections occur. CYBA mutations lead to one of the autosomal recessive forms of chronic granulomatous disease (AR220CGD) clinically characterized by recurrent and severe infections in early childhood. However, p22phox is also the partner of NOX1, NOX3 and NOX4, but not NOX5, which are analogs of NOX2, the first identified member of the NOX family. P22phox–NOX complexes have emerged as one of the most relevant sources of reactive oxygen species (ROS) in tissues and cells, and are associated with several diseases such as cardiovascular and cerebrovascular diseases. The p22phox-deficient mouse strain nmf333 has made it possible to highlight the role of p22phox in the control of inner ear balance in association with NOX3. However, the relevance of p22phox for NOX3 function remains uncertain because AR220CGD patients do not suffer from vestibular dysfunction. Finally, a large number of genetic variations of CYBA have been reported, among them the C242T polymorphism, which has been extensively studied in association with coronary artery and heart diseases, but conflicting results continue to be reported.

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