URL of this page: https://medlineplus.gov/genetics/gene/ncf1/

NCF1 gene

neutrophil cytosolic factor 1

Normal Function

The NCF1 gene provides instructions for making a protein called neutrophil cytosolic factor 1 (also known as p47-phox). This protein is one part (subunit) of a group of proteins that forms an enzyme complex called NADPH oxidase (NOX), which plays an essential role in the immune system. NOX is primarily active in immune system cells called phagocytes. These cells catch and destroy foreign invaders such as bacteria and fungi. NOX 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 NOX. 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 (ROS). Phagocytes use these substances to kill foreign invaders, preventing them from reproducing in the body and causing illness.

NOX plays a role in other cell types as well, such as blood vessel cells. Abnormal blood flow in blood vessels can trigger these cells to make more NOX, which stimulates the production of ROS. These compounds can influence blood pressure and other biological processes.

Health Conditions Related to Genetic Changes

Chronic granulomatous disease

Variants (also known as mutations) in the NCF1 gene account for about 25 percent of cases of 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. The variants that cause this disorder occur in both copies of the NCF1 gene in each cell. Ninety-five percent of affected individuals have a variant known as delta GT that deletes two DNA building blocks from the NCF1 gene in an area called exon 2 (written as 75_76delGT). This genetic change leads to the production of an abnormally short, nonfunctional version of neutrophil cytosolic factor 1. Other, less common variants also disrupt the function or production of neutrophil cytosolic factor 1. Without this protein, NOX cannot assemble or function properly. As a result, phagocytes are unable to produce ROS to kill foreign invaders, and neutrophil activity is not regulated. A lack of NOX leaves affected individuals vulnerable to many types of infection and excessive inflammation.

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Williams syndrome

The NCF1 gene is located in a region of chromosome 7 that is often deleted in people with Williams syndrome. Williams syndrome is a developmental disorder that affects many parts of the body. As a result of the deletion of part of chromosome 7, some people with this condition are missing one copy of the NCF1 gene in each cell. Researchers have found that the loss of this gene is a protective factor that appears to lower the risk of developing high blood pressure (hypertension). People with Williams syndrome whose NCF1 gene is not deleted have a higher risk of developing hypertension.

People with only one copy of the NCF1 gene have reduced levels of the neutrophil cytosolic factor 1 protein, which decreases the activity of NOX and results in the production of fewer ROS. Studies suggest that ROS play an important role in blood vessel changes related to hypertension.

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Other Names for This Gene

  • NCF1_HUMAN
  • p47-phox
  • p47phox
  • SH3PXD1A

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

  • Babior BM, Lambeth JD, Nauseef W. The neutrophil NADPH oxidase. Arch Biochem Biophys. 2002 Jan 15;397(2):342-4. Review. Citation on PubMed
  • Chanock SJ, Roesler J, Zhan S, Hopkins P, Lee P, Barrett DT, Christensen BL, Curnutte JT, Görlach A. Genomic structure of the human p47-phox (NCF1) gene. Blood Cells Mol Dis. 2000 Feb;26(1):37-46. Citation on PubMed
  • Del Campo M, Antonell A, Magano LF, Muñoz FJ, Flores R, Bayés M, Pérez Jurado LA. Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension. Am J Hum Genet. 2006 Apr;78(4):533-42. Epub 2006 Jan 31. Citation on PubMed or Free article on PubMed Central
  • Jurkowska M, Bernatowska E, Bal J. Genetic and biochemical background of chronic granulomatous disease. Arch Immunol Ther Exp (Warsz). 2004 Mar-Apr;52(2):113-20. Review. Citation on PubMed
  • Kannengiesser C, Gérard B, El Benna J, Henri D, Kroviarski Y, Chollet-Martin S, Gougerot-Pocidalo MA, Elbim C, Grandchamp B. Molecular epidemiology of chronic granulomatous disease in a series of 80 kindreds: identification of 31 novel mutations. Hum Mutat. 2008 Sep;29(9):E132-49. doi: 10.1002/humu.20820. Citation on PubMed
  • Lassègue B, Griendling KK. NADPH oxidases: functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):653-61. doi: 10.1161/ATVBAHA.108.181610. Epub 2009 Nov 12. Review. Citation on PubMed
  • Roesler J, Curnutte JT, Rae J, Barrett D, Patino P, Chanock SJ, Goerlach A. Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease. Blood. 2000 Mar 15;95(6):2150-6. Citation on PubMed
  • Roos D, de Boer M, Köker MY, Dekker J, Singh-Gupta V, Ahlin A, Palmblad J, Sanal O, Kurenko-Deptuch M, Jolles S, Wolach B. Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47phox component of the phagocyte NADPH oxidase. Hum Mutat. 2006 Dec;27(12):1218-29. Citation on PubMed
  • Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, van Leeuwen K, Köker 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. Review. Citation on PubMed or Free article on PubMed Central
  • Stasia MJ, Li XJ. Genetics and immunopathology of chronic granulomatous disease. Semin Immunopathol. 2008 Jul;30(3):209-35. doi: 10.1007/s00281-008-0121-8. Epub 2008 May 29. Review. Citation on PubMed
  • 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. Review. Erratum in: FEBS J. 2008 Aug;275(15):3984. Citation on PubMed
  • Vázquez N, Lehrnbecher T, Chen R, Christensen BL, Gallin JI, Malech H, Holland S, Zhu S, Chanock SJ. Mutational analysis of patients with p47-phox-deficient chronic granulomatous disease: The significance of recombination events between the p47-phox gene (NCF1) and its highly homologous pseudogenes. Exp Hematol. 2001 Feb;29(2):234-43. Citation on PubMed

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