FAS Gene: History
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Subjects: Genetics & Heredity
Contributor:
Vivi Li

Fas cell surface death receptor

  • genes

1. Normal Function

The FAS gene provides instructions for making a protein that is involved in cell signaling. Three FAS proteins group together to form a structure called a trimer, which then interacts with other molecules to perform its signaling function. This signaling initiates a process called a caspase cascade. The caspase cascade is a series of steps that results in the self-destruction of cells (apoptosis) when they are not needed.

2. Health Conditions Related to Genetic Changes

2.1 Autoimmune Lymphoproliferative Syndrome

At least 115 mutations in the FAS gene have been identified in people with a disorder of the immune system called autoimmune lymphoproliferative syndrome (ALPS). ALPS is characterized by the production of an abnormally large number of immune system cells (lymphocytes), resulting in enlargement of the lymph nodes (lymphadenopathy), the liver (hepatomegaly), and the spleen (splenomegaly). Autoimmune disorders, in which the immune system malfunctions and attacks the body's own tissues and organs, are also common in ALPS. People with ALPS have an increased risk of developing cancer of the immune system cells (lymphoma).

When the immune system is activated to fight an infection, large numbers of lymphocytes are produced. Normally, these lymphocytes undergo apoptosis when they are no longer required. FAS gene mutations lead to an abnormal trimer that interferes with the initiation of apoptosis. As a result, excess lymphocytes accumulate in the body's tissues and organs and often begin attacking them, leading to autoimmune disorders. Interference with apoptosis allows cells to multiply without control, leading to the lymphomas that occur in people with this disorder.

2.2 Juvenile idiopathic arthritis

2.3 Cancers

Studies have associated certain FAS gene variations with increased risk of developing cancer, including cancers of the lung, breast, and esophagus. Researchers believe that these variations may affect the signaling that initiates apoptosis, increasing the risk that cells will multiply out of control and result in cancer.

3. Other Names for This Gene

  • APO-1

  • apo-1 antigen

  • APO-1 cell surface antigen

  • apoptosis antigen 1

  • apoptosis-mediating surface antigen FAS

  • APT1

  • CD95

  • CD95 antigen

  • Fas (TNF receptor superfamily, member 6)

  • Fas AMA

  • Fas antigen

  • FAS1

  • FASLG receptor

  • TNFRSF6

  • TNR6_HUMAN

  • tumor necrosis factor receptor superfamily member 6

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/fas

References

  1. Cao Y, Miao XP, Huang MY, Deng L, Lin DX, Zeng YX, Shao JY. Polymorphisms ofdeath pathway genes FAS and FASL and risk of nasopharyngeal carcinoma. MolCarcinog. 2010 Nov;49(11):944-50. doi: 10.1002/mc.20676.
  2. Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB, Puck JM,Jaffe ES, Pittaluga S, Cohen JI, Fleisher TA, Rao VK. Somatic FAS mutations arecommon in patients with genetically undefined autoimmune lymphoproliferativesyndrome. Blood. 2010 Jun 24;115(25):5164-9. doi: 10.1182/blood-2010-01-263145.
  3. Fleisher TA, Straus SE, Bleesing JJ. A genetic disorder of lymphocyteapoptosis involving the fas pathway: the autoimmune lymphoproliferative syndrome.Curr Allergy Asthma Rep. 2001 Nov;1(6):534-40. Review.
  4. Fleisher TA. The autoimmune lymphoproliferative syndrome: an experiment ofnature involving lymphocyte apoptosis. Immunol Res. 2008;40(1):87-92. doi:10.1007/s12026-007-8001-1.
  5. Poppema S, Maggio E, van den Berg A. Development of lymphoma in AutoimmuneLymphoproliferative Syndrome (ALPS) and its relationship to Fas gene mutations.Leuk Lymphoma. 2004 Mar;45(3):423-31. Review.
  6. Randhawa SR, Chahine BG, Lowery-Nordberg M, Cotelingam JD, Casillas AM.Underexpression and overexpression of Fas and Fas ligand: a double-edged sword.Ann Allergy Asthma Immunol. 2010 Apr;104(4):286-92. doi:10.1016/j.anai.2010.01.021. Review.
  7. Rieux-Laucat F. Inherited and acquired death receptor defects in humanAutoimmune Lymphoproliferative Syndrome. Curr Dir Autoimmun. 2006;9:18-36.Review.
  8. Sun T, Miao X, Zhang X, Tan W, Xiong P, Lin D. Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma. J Natl Cancer Inst.2004 Jul 7;96(13):1030-6.
  9. Teachey DT, Seif AE, Grupp SA. Advances in the management and understanding ofautoimmune lymphoproliferative syndrome (ALPS). Br J Haematol. 2010Jan;148(2):205-16. doi: 10.1111/j.1365-2141.2009.07991.x.Review.
  10. Turbyville JC, Rao VK. The autoimmune lymphoproliferative syndrome: A raredisorder providing clues about normal tolerance. Autoimmun Rev. 2010May;9(7):488-93. doi: 10.1016/j.autrev.2010.02.007.
  11. Worth A, Thrasher AJ, Gaspar HB. Autoimmune lymphoproliferative syndrome:molecular basis of disease and clinical phenotype. Br J Haematol. 2006Apr;133(2):124-40. Review.
  12. Zhang B, Sun T, Xue L, Han X, Zhang B, Lu N, Shi Y, Tan W, Zhou Y, Zhao D,Zhang X, Guo Y, Lin D. Functional polymorphisms in FAS and FASL contribute toincreased apoptosis of tumor infiltration lymphocytes and risk of breast cancer. Carcinogenesis. 2007 May;28(5):1067-73.
  13. Zhang X, Miao X, Sun T, Tan W, Qu S, Xiong P, Zhou Y, Lin D. Functionalpolymorphisms in cell death pathway genes FAS and FASL contribute to risk of lungcancer. J Med Genet. 2005 Jun;42(6):479-84.
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