chronic granulomatous disease More than 40 mutations in the CYBA gene have been found to cause chronic granulomatous disease. People with this disorder are at increased risk of developing recurrent episodes of infection and inflammation due to a weakened immune system. Mutations in the CYBA gene cause less than 5 percent of all cases of this condition. Most of these mutations change single building blocks of protein (amino acids) in the cytochrome b-245 alpha chain or cause it to be abnormally short and nonfunctional. An altered protein not only diminishes the function of the alpha chain, but the function of its beta 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 foreign invaders, and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation.

     The CYBA gene provides instructions for making a protein called the cytochrome b-245 alpha chain (also known as p22-phox). This protein is one part (subunit) of a group of proteins that forms an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Within this complex, the cytochrome b-245 alpha chain has a beta chain partner (produced from the CYBB 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 immune system cells called phagocytes. These cells catch and destroy foreign invaders such as bacteria and fungi. NADPH oxidase is also thought to regulate the activity of immune cells called neutrophils. These cells play a role in adjusting the inflammatory response to optimize healing and reduce injury to the body. The presence of foreign invaders stimulates phagocytes and triggers the assembly of NADPH oxidase . This enzyme participates in a chemical reaction that converts oxygen to a toxic molecule called superoxide. Superoxide is used to generate several other compounds, including hydrogen peroxide (a strong disinfectant) and hypochlorous acid (the active ingredient in bleach). These highly reactive, toxic substances are known as reactive oxygen species. Phagocytes use these substances to kill foreign invaders, preventing them from reproducing in the body and causing illness.

The following transcription factors affect gene expression:

• NF-kappaB
• PPAR-gamma1
• PPAR-gamma2
• p53
• AP-1
• c-Jun
• NF-kappaB1
• c-Myc
• Sp1

Molecular Function:

• Electron Carrier Activity
• Heme Binding
• Metal Ion Binding
• Protein Heterodimerization Activity
• Sh3 Domain Binding
• Superoxide-Generating Nadph Oxidase Activity

Biological Processes:

• Antigen Processing And Presentation Of Exogenous Peptide Antigen Via Mhc Class I, Tap-Dependent
• Cell Redox Homeostasis
• Cellular Response To Angiotensin
• Cellular Response To Gamma Radiation
• Cellular Response To Glucose Stimulus
• Cellular Response To L-Glutamine
• Cellular Response To Mechanical Stimulus
• Cellular Response To Organic Cyclic Compound
• Cellular Response To Tumor Necrosis Factor
• Cytochrome Complex Assembly
• Hydrogen Peroxide Biosynthetic Process
• Inflammatory Response
• Innate Immune Response
• Negative Regulation Of Glomerular Filtration By Angiotensin
• Oxidation-Reduction Process
• Positive Regulation Of Cell Growth
• Positive Regulation Of Defense Response To Bacterium
• Positive Regulation Of Endothelial Cell Proliferation
• Positive Regulation Of Interleukin-6 Production
• Positive Regulation Of Mucus Secretion
• Positive Regulation Of Nad(P)H Oxidase Activity
• Positive Regulation Of Phagocytosis
• Positive Regulation Of Reactive Oxygen Species Biosynthetic Process
• Positive Regulation Of Smooth Muscle Cell Proliferation
• Positive Regulation Of Superoxide Anion Generation
• Positive Regulation Of Toll-Like Receptor 2 Signaling Pathway
• Positive Regulation Of Tumor Necrosis Factor Production
• Regulation Of Release Of Sequestered Calcium Ion Into Cytosol
• Respiratory Burst
• Response To Aldosterone
• Response To Hypoxia
• Response To Interleukin-1
• Response To Nutrient Levels
• Response To Reactive Oxygen Species
• Smooth Muscle Hypertrophy
• Superoxide Anion Generation
• Superoxide Metabolic Process
• Vascular Endothelial Growth Factor Receptor Signaling Pathway
• Cellular Response To Amino Acid Stimulus

Drug Bank:

• Dextromethorphan