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Genetics Home Reference: your guide to understanding genetic conditions
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NCF2

Reviewed August 2012

What is the official name of the NCF2 gene?

The official name of this gene is “neutrophil cytosolic factor 2.”

NCF2 is the gene's official symbol. The NCF2 gene is also known by other names, listed below.

What is the normal function of the NCF2 gene?

The NCF2 gene provides instructions for making a protein called neutrophil cytosolic factor 2 (also known as p67-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.

Does the NCF2 gene share characteristics with other genes?

The NCF2 gene belongs to a family of genes called TTC (tetratricopeptide (TTC) repeat domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the NCF2 gene related to health conditions?

chronic granulomatous disease - caused by mutations in the NCF2 gene

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.

autoimmune disorders - increased risk from variations of the NCF2 gene

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.

Where is the NCF2 gene located?

Cytogenetic Location: 1q25

Molecular Location on chromosome 1: base pairs 183,555,561 to 183,590,920

The NCF2 gene is located on the long (q) arm of chromosome 1 at position 25.

The NCF2 gene is located on the long (q) arm of chromosome 1 at position 25.

More precisely, the NCF2 gene is located from base pair 183,555,561 to base pair 183,590,920 on chromosome 1.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about NCF2?

You and your healthcare professional may find the following resources about NCF2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the NCF2 gene or gene products?

  • NADPH oxidase activator 2
  • NCF-2
  • NCF2_HUMAN
  • neutrophil cytosol factor 2
  • NOXA2
  • P67PHOX
  • P67-PHOX

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding NCF2?

acids ; autoimmune ; bacteria ; chronic ; cytosol ; DNA ; enzyme ; gene ; granulomatous ; hydrogen peroxide ; hypochlorous acid ; immune system ; infection ; inflammation ; injury ; innate immunity ; lupus ; molecule ; neutrophils ; oxidase ; oxygen ; phagocytes ; protein ; reactive oxygen species ; subunit ; systemic lupus ; systemic lupus erythematosus ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Cunninghame Graham DS, Morris DL, Bhangale TR, Criswell LA, Syvänen AC, Rönnblom L, Behrens TW, Graham RR, Vyse TJ. Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genet. 2011 Oct;7(10):e1002341. doi: 10.1371/journal.pgen.1002341. Epub 2011 Oct 27. (http://www.ncbi.nlm.nih.gov/pubmed/22046141?dopt=Abstract)
  • Jacob CO, Eisenstein M, Dinauer MC, Ming W, Liu Q, John S, Quismorio FP Jr, Reiff A, Myones BL, Kaufman KM, McCurdy D, Harley JB, Silverman E, Kimberly RP, Vyse TJ, Gaffney PM, Moser KL, Klein-Gitelman M, Wagner-Weiner L, Langefeld CD, Armstrong DL, Zidovetzki R. Lupus-associated causal mutation in neutrophil cytosolic factor 2 (NCF2) brings unique insights to the structure and function of NADPH oxidase. Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):E59-67. doi: 10.1073/pnas.1113251108. Epub 2011 Dec 27. (http://www.ncbi.nlm.nih.gov/pubmed/22203994?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18546332?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4688)
  • OMIM: NEUTROPHIL CYTOSOLIC FACTOR 2 (http://omim.org/entry/608515)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/20167518?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18509647?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18513324?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2012
Published: August 18, 2014