NCF2

More than 50 mutations in the NCF2 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 NCF2 gene cause less than 5 percent of all cases of this condition. These mutations change single protein building blocks (amino acids) in the neutrophil cytosolic factor 2 protein, which cause the protein to be abnormally short and nonfunctional or alter its 3-dimensional structure. All of these mutations decrease the function of the neutrophil cytosolic factor 2 protein or prevent its production. Without this protein, 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.

Studies suggest that certain normal variations in the NCF2 gene can increase the risk of a condition called systemic lupus erythematosus. This condition is one of a group of related diseases known as autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs. The variants associated with increased risk of systemic lupus erythematosus change single DNA building blocks (nucleotides) in the NCF2 gene. These changes are thought to result in the production of a neutrophil cytosolic factor 2 protein with an altered function that impairs the function of NADPH oxidase. As a result, fewer reactive oxygen species are produced when foreign invaders trigger an immune reaction. This lack of reactive oxygen species causes the body to overcompensate by activating more immune cells and producing more immune proteins. The overactive immune reaction increases the risk that the immune cells will attack the body's tissues and organs, causing systemic lupus erythematosus. Researchers believe that a combination of genetic and environmental factors play a role in development of this complex condition.