Alt. symbols: CGD | GP91-PHOX | NOX2

Approved name: cytochrome b-245 beta chain
Alt. names: chronic granulomatous disease, cytochrome b-245, beta polypeptide | NADPH oxidase 2

Location: Xp21.1: 37780018 - 37813461 (+)
Gene type: protein_coding, 6 transcripts.

Scores: LoFtool: 0.010500 | pLI: 0.99769790 | LOEUF: 0.193

HGNC: 2578

NCBI: 1536, RefSeq: NG_009065.1

Ensembl: ENSG00000165168.9

LRG_53 | Status: public

OMIM: 300481

Expression | ProteinAtlas

The CYBB gene encodes the protein NADPH oxidase 2 (Nox2), also known as cytochrome b(558) subunit beta, or cytochrome b-245 beta chain, or p91-phox. This protein is a subunit of the NADPH oxidase enzyme complex, which plays an essential role in the immune system. Within this complex, the cytochrome b-245 beta chain has an alpha chain partner (produced from the CYBA gene). Both alpha and beta chains are required for either to function, and the NADPH oxidase complex requires both chains in order to be functional. NADPH oxidase is primarily active in phagocytes, which attack bacteria and fungi pathogens. NADPH oxidase is also thought to regulate the activity of neutrophils. These cells play a role in adjusting the inflammatory response to optimize healing and reduce injury to the body. The presence of pathogens stimulates phagocytes and triggers the assembly of NADPH oxidase. This enzyme participates in a chemical reaction that converts oxygen to superoxide (toxic). Superoxide is used to generate several other compounds, including hydrogen peroxide and hypochlorous acid. These highly reactive, toxic substances, known as reactive oxygen species, are used by phagocytes to kill invading fungi and bacteria.

Mutations in the CYBB gene cause x-linked chronic granulomatous disease (CGD) [MIM:306400], but also X-linked Immunodeficiency 34 with mycobacteriosis [MIM:300645] (Bustamante et al., 2011, 2007). The condition primarily affects males as it is inherited in an X-linked recessive manner. Females, who very rarely present one mutated CYBB allele, have mild symptoms of chronic granulomatous disease, such as an increased frequency of bacterial or fungal infections. More than 650 mutations in the CYBB gene have been found to cause chronic granulomatous disease to date. People with this disorder are at increased risk of developing recurrent episodes of infection and inflammation. Mutations in the CYBB gene cause approximately 70 percent of all cases of CGD. Most of these mutations are missense, although nonsense, frameshift and splice-site mutations have also been described. An altered cytochrome b-245 beta subunit not only diminishes its function, but the function of its alpha chain partner as well. Without these subunits, NADPH oxidase cannot assemble or function properly. As a result, phagocytes are unable to produce reactive oxygen species to kill pathogens, and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation. [Load More]