Reviewed March 2013
What is the official name of the APC gene?
The official name of this gene is “adenomatous polyposis coli.”
APC is the gene's official symbol. The APC gene is also known by other names, listed below.
What is the normal function of the APC gene?
The APC gene provides instructions for making the APC protein, which plays a critical role in several cellular processes. The APC protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. It helps control how often a cell divides, how it attaches to other cells within a tissue, and whether a cell moves within or away from a tissue. This protein also helps ensure that the number of chromosomes in a cell is correct following cell division. The APC protein accomplishes these tasks mainly through association with other proteins, especially those that are involved in cell attachment and signaling.
One protein with which APC associates is beta-catenin. Beta-catenin helps control the activity (expression) of particular genes and promotes the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation). Beta-catenin also helps cells attach to one another and is important for tissue formation. Association of APC with beta-catenin signals for beta-catenin to be broken down when it is no longer needed.
How are changes in the APC gene related to health conditions?
- desmoid tumor - caused by mutations in the APC gene
Several mutations in the APC gene have been found in people with a type of aggressive but noncancerous (benign) growth called a desmoid tumor. These rare tumors arise from connective tissue, which provides strength and flexibility to structures such as bones, ligaments, and muscles. APC gene mutations typically cause formation of desmoid tumors in the abdomen, but these tumors can also occur in other parts of the body. Although APC-related desmoid tumors are commonly associated with a form of colon cancer called familial adenomatous polyposis (described below), APC gene mutations can cause tumors in individuals without this inherited disease. APC gene mutations are found in about 10 to 15 percent of non-inherited (sporadic) desmoid tumors; these mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells.
Most APC gene mutations that cause sporadic desmoid tumors lead to an abnormally short APC protein. The shortened protein is unable to interact with the beta-catenin protein, which prevents the breakdown of beta-catenin when it is no longer needed. Excess beta-catenin promotes uncontrolled growth and division of cells, allowing the formation of desmoid tumors.
- familial adenomatous polyposis - caused by mutations in the APC gene
More than 700 mutations in the APC gene have been identified in families with the classic and attenuated types of familial adenomatous polyposis (FAP). Most of these mutations lead to the production of an abnormally short, nonfunctional version of the APC protein. This short protein cannot suppress the cellular overgrowth that leads to the formation of abnormal growths (polyps) in the colon, which can become cancerous. The most common mutation in FAP is a deletion of five building blocks of DNA (nucleotides) in the APC gene. This mutation changes the sequence of the building blocks of proteins (amino acids) in the resulting APC protein.
Although most people with FAP will develop colorectal cancer, the number of polyps and the time frame in which they become cancerous depend on the location of the mutation in the APC gene. The location of the mutation also determines whether an individual with FAP is predisposed to developing desmoid tumors (described above).
- other cancers - increased risk from variations of the APC gene
Mutations in the APC gene are also responsible for a disorder called Turcot syndrome, which is closely related to familial adenomatous polyposis. Turcot syndrome is an association of colorectal cancer with a type of cancerous brain tumor called a medulloblastoma. Approximately two-thirds of people with Turcot syndrome have mutations in the APC gene.
A certain mutation in the APC gene (unrelated to Turcot syndrome) is found in approximately 6 percent of people with Ashkenazi (eastern and central European) Jewish heritage. This mutation replaces the amino acid isoleucine with the amino acid lysine at position 1307 in the APC protein (written as Ile1307Lys or I1307K). This change was initially thought to be harmless, but has been shown to be associated with a 10 percent to 20 percent increased risk of colon cancer.
Somatic mutations in the APC gene may be involved in the development of a small percentage of stomach (gastric) cancers.
Where is the APC gene located?
Cytogenetic Location: 5q21-q22
Molecular Location on chromosome 5: base pairs 112,707,505 to 112,846,239
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/324))
The APC gene is located on the long (q) arm of chromosome 5 between positions 21 and 22.
More precisely, the APC gene is located from base pair 112,707,505 to base pair 112,846,239 on chromosome 5.
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 APC?
You and your healthcare professional may find the following resources about APC helpful.
Educational resources - Information pages
- American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer (http://www.nchpeg.org/documents/crc/Basics%20of%20genetic%20testing.pdf)
- Cancer Medicine (sixth edition, 2003): The APC Gene (http://www.ncbi.nlm.nih.gov/books/NBK13499/)
- Madame Curie Bioscience Database (2000): Nuclear APC (http://www.ncbi.nlm.nih.gov/books/NBK6410/)
- National Cancer Institute: Genetics of Colorectal Cancer (http://www.cancer.gov/types/colorectal/hp/colorectal-genetics-pdq)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1345)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for APC (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=324%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28APC%5BTI%5D%29%20OR%20%28adenomatosis%20polyposis%20coli%5BTI%5D%29%29%20AND%20%28apc%20gene%5BMAJR%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20360%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- APC GENE (http://omim.org/entry/611731)
- GASTRIC CANCER, HEREDITARY DIFFUSE (http://omim.org/entry/137215)
- MISMATCH REPAIR CANCER SYNDROME (http://omim.org/entry/276300)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/APCID118.html)
- HGNC Gene Family: Armadillo repeat containing (http://www.genenames.org/cgi-bin/genefamilies/set/409)
- HGNC Gene Family: Protein phosphatase 1 regulatory subunits (http://www.genenames.org/cgi-bin/genefamilies/set/694)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=583)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/324)
What other names do people use for the APC gene or gene products?
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 APC?
amino acid ;
cell division ;
connective tissue ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Brueckl WM, Ballhausen WG, Förtsch T, Günther K, Fiedler W, Gentner B, Croner R, Boxberger F, Kirchner T, Hahn EG, Hohenberger W, Wein A. Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma. Dis Colon Rectum. 2005 Jun;48(6):1275-81. (http://www.ncbi.nlm.nih.gov/pubmed/15793634?dopt=Abstract)
- Ceol CJ, Pellman D, Zon LI. APC and colon cancer: two hits for one. Nat Med. 2007 Nov;13(11):1286-7. (http://www.ncbi.nlm.nih.gov/pubmed/17987022?dopt=Abstract)
- Cohen MM Jr. Molecular dimensions of gastrointestinal tumors: some thoughts for digestion. Am J Med Genet A. 2003 Nov 1;122A(4):303-14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14518068?dopt=Abstract)
- Couture J, Mitri A, Lagace R, Smits R, Berk T, Bouchard HL, Fodde R, Alman B, Bapat B. A germline mutation at the extreme 3' end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta-catenin in the desmoid tumor. Clin Genet. 2000 Mar;57(3):205-12. (http://www.ncbi.nlm.nih.gov/pubmed/10782927?dopt=Abstract)
- Fodde R. The APC gene in colorectal cancer. Eur J Cancer. 2002 May;38(7):867-71. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11978510?dopt=Abstract)
- Goss KH, Groden J. Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol. 2000 May;18(9):1967-79. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10784639?dopt=Abstract)
- Jaiswal AS, Balusu R, Narayan S. Involvement of adenomatous polyposis coli in colorectal tumorigenesis. Front Biosci. 2005 May 1;10:1118-34. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15769611?dopt=Abstract)
- Järvinen HJ, Peltomäki P. The complex genotype-phenotype relationship in familial adenomatous polyposis. Eur J Gastroenterol Hepatol. 2004 Jan;16(1):5-8. (http://www.ncbi.nlm.nih.gov/pubmed/15095846?dopt=Abstract)
- Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009 Jan;35(1):3-10. doi: 10.1016/j.ejso.2008.07.003. Epub 2008 Aug 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18722078?dopt=Abstract)
- Middleton SB, Frayling IM, Phillips RK. Desmoids in familial adenomatous polyposis are monoclonal proliferations. Br J Cancer. 2000 Feb;82(4):827-32. (http://www.ncbi.nlm.nih.gov/pubmed/10732754?dopt=Abstract)
- Näthke IS. The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Annu Rev Cell Dev Biol. 2004;20:337-66. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15473844?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/324)
- Scott RJ, Froggatt NJ, Trembath RC, Evans DG, Hodgson SV, Maher ER. Familial infiltrative fibromatosis (desmoid tumours) (MIM135290) caused by a recurrent 3' APC gene mutation. Hum Mol Genet. 1996 Dec;5(12):1921-4. (http://www.ncbi.nlm.nih.gov/pubmed/8968744?dopt=Abstract)
- Sena P, Saviano M, Monni S, Losi L, Roncucci L, Marzona L, De Pol A. Subcellular localization of beta-catenin and APC proteins in colorectal preneoplastic and neoplastic lesions. Cancer Lett. 2006 Sep 28;241(2):203-12. Epub 2005 Nov 17. (http://www.ncbi.nlm.nih.gov/pubmed/16298038?dopt=Abstract)
- Senda T, Shimomura A, Iizuka-Kogo A. Adenomatous polyposis coli (Apc) tumor suppressor gene as a multifunctional gene. Anat Sci Int. 2005 Sep;80(3):121-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16158975?dopt=Abstract)
- Tejpar S, Michils G, Denys H, Van Dam K, Nik SA, Jadidizadeh A, Cassiman JJ. Analysis of Wnt/Beta catenin signalling in desmoid tumors. Acta Gastroenterol Belg. 2005 Jan-Mar;68(1):5-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15832580?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.