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URL of this page: https://medlineplus.gov/genetics/gene/ncf4/

NCF4 gene

neutrophil cytosolic factor 4

Normal Function

The NCF4 gene provides instructions for making a protein called neutrophil cytosolic factor 4 (also known as p40-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. Specifically, 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.

Health Conditions Related to Genetic Changes

Chronic granulomatous disease

At least two mutations in the NCF4 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 NCF4 gene are a rare cause of this condition. These mutations result in a decrease in functional NADPH oxidase. A shortage (deficiency) of this protein impairs the assembly or function of NADPH oxidase. 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.

More About This Health Condition

Other Names for This Gene

  • NCF
  • NCF-4
  • NCF4_HUMAN
  • neutrophil cytosol factor 4
  • neutrophil cytosolic factor 4, 40kDa
  • neutrophil NADPH oxidase factor 4
  • p40-phox
  • P40PHOX

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, Marchal CC, Stull ND, Lewis DB, Steele M, Kellner JD, Yu W, Meroueh SO, Nauseef WM, Dinauer MC. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009 Oct 8;114(15):3309-15. doi: 10.1182/blood-2009-07-231498. Epub 2009 Aug 19. Citation on PubMed or Free article on PubMed Central
  • Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, van Leeuwen K, Koker MY, Wolach B, Roesler J, Malech HL, Holland SM, Gallin JI, Stasia MJ. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis. 2010 Apr 15;44(4):291-9. doi: 10.1016/j.bcmd.2010.01.009. Epub 2010 Feb 18. Citation on PubMed or Free article on PubMed Central
  • Sumimoto H. Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species. FEBS J. 2008 Jul;275(13):3249-77. doi: 10.1111/j.1742-4658.2008.06488.x. Epub 2008 May 30. Erratum In: FEBS J. 2008 Aug;275(15):3984. Citation on PubMed

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