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Genetics Home Reference: your guide to understanding genetic conditions
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EPCAM

Reviewed May 2013

What is the official name of the EPCAM gene?

The official name of this gene is “epithelial cell adhesion molecule.”

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

What is the normal function of the EPCAM gene?

The EPCAM gene provides instructions for making a protein known as epithelial cellular adhesion molecule (EpCAM). This protein is found in epithelial cells, which are the cells that line the surfaces and cavities of the body. The EpCAM protein is found spanning the membrane that surrounds epithelial cells, where it helps cells stick to one another (cell adhesion). In addition, the protein in the cell membrane can be cut at a specific location, releasing a piece called the intracellular domain (EpICD), which helps relay signals from outside the cell to the nucleus of the cell. EpICD travels to the nucleus and associates with other proteins, forming a group (complex) that regulates the activity of several genes that are involved in cell growth and division (proliferation), maturation (differentiation), and movement (migration), all of which are important processes for the proper development of cells and tissues.

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

Lynch syndrome - increased risk from variations of the EPCAM gene

Certain mutations in the EPCAM gene are associated with Lynch syndrome, a condition that increases the risk of developing many types of cancer, particularly cancers of the large intestine (colon) and the rectum (collectively called colorectal cancer). These mutations account for up to 6 percent of Lynch syndrome cases. On chromosome 2, the EPCAM gene lies next to another gene called MSH2. Each gene provides instructions for making an individual messenger RNA (mRNA), which serves as the genetic blueprint for making the protein. The EPCAM gene mutations involved in Lynch syndrome remove a region that signals the end of the gene, which leads to formation of a long mRNA that includes both EPCAM and MSH2.

For unknown reasons, these EPCAM gene mutations cause the MSH2 gene to be turned off (inactivated) by a mechanism known as promoter hypermethylation. The promoter is a region of DNA near the beginning of the gene that controls gene activity (expression). Hypermethylation occurs when too many small molecules called methyl groups are attached to the promoter region. The extra methyl groups attached to the MSH2 promoter reduce the expression of the MSH2 gene, which means that less protein is produced in epithelial cells.

The MSH2 protein plays an essential role in repairing mistakes in DNA; loss of this protein prevents proper DNA repair, and mistakes accumulate as the cells continue to divide. These mistakes can lead to uncontrolled cell growth and increase the risk of cancer.

other disorders - caused by mutations in the EPCAM gene

Mutations in the EPCAM gene can also cause congenital tufting enteropathy. This condition is characterized by abnormal development of epithelial cells in the intestines. In this condition, the villi, which are small finger-like projections that line the small intestine, are abnormal. In particular, they have "tufts" of extra epithelial cells on their tips. Normally, these projections provide a greatly increased surface area to absorb nutrients. The altered villi are less able to absorb nutrients and fluids than normal tissue, which causes life-threatening diarrhea and poor growth. Congenital tufting enteropathy develops in newborns within days of birth and lasts throughout life. EPCAM gene mutations involved in this condition lead to the loss of functional EpCAM protein. The resulting loss of EpICD signaling leads to abnormal development of intestinal epithelial cells, causing congenital tufting enteropathy.

Where is the EPCAM gene located?

Cytogenetic Location: 2p21

Molecular Location on chromosome 2: base pairs 47,369,147 to 47,387,027

The EPCAM gene is located on the short (p) arm of chromosome 2 at position 21.

The EPCAM gene is located on the short (p) arm of chromosome 2 at position 21.

More precisely, the EPCAM gene is located from base pair 47,369,147 to base pair 47,387,027 on chromosome 2.

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 EPCAM?

You and your healthcare professional may find the following resources about EPCAM 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 EPCAM gene or gene products?

  • 17-1A
  • 323/A3
  • CD326
  • CO-17A
  • EGP-2
  • EGP34
  • EGP40
  • Ep-CAM
  • epithelial cell adhesion molecule precursor
  • epithelial glycoprotein 314
  • ESA
  • GA733-2
  • HEA125
  • human epithelial glycoprotein-2
  • KS1/4
  • KSA
  • Ly74
  • M4S1
  • MH99
  • MIC18
  • MK-1
  • MOC31
  • TACST-1
  • TACSTD1
  • TROP1
  • tumor-associated calcium signal transducer 1

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 EPCAM?

adhesion molecule ; calcium ; cancer ; cell ; cell adhesion ; cell membrane ; chromosome ; colon ; colorectal ; congenital ; differentiation ; DNA ; DNA repair ; domain ; epithelial ; gene ; intestine ; intracellular ; messenger RNA ; methyl ; molecule ; mRNA ; nucleus ; proliferation ; promoter ; promoter region ; protein ; rectum ; RNA ; syndrome ; tissue ; tumor

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

References

  • Kuiper RP, Vissers LE, Venkatachalam R, Bodmer D, Hoenselaar E, Goossens M, Haufe A, Kamping E, Niessen RC, Hogervorst FB, Gille JJ, Redeker B, Tops CM, van Gijn ME, van den Ouweland AM, Rahner N, Steinke V, Kahl P, Holinski-Feder E, Morak M, Kloor M, Stemmler S, Betz B, Hutter P, Bunyan DJ, Syngal S, Culver JO, Graham T, Chan TL, Nagtegaal ID, van Krieken JH, Schackert HK, Hoogerbrugge N, van Kessel AG, Ligtenberg MJ. Recurrence and variability of germline EPCAM deletions in Lynch syndrome. Hum Mutat. 2011 Apr;32(4):407-14. doi: 10.1002/humu.21446. Epub 2011 Mar 1. (http://www.ncbi.nlm.nih.gov/pubmed/21309036?dopt=Abstract)
  • Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, Lee TY, Bodmer D, Hoenselaar E, Hendriks-Cornelissen SJ, Tsui WY, Kong CK, Brunner HG, van Kessel AG, Yuen ST, van Krieken JH, Leung SY, Hoogerbrugge N. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet. 2009 Jan;41(1):112-7. doi: 10.1038/ng.283. Epub 2008 Dec 21. (http://www.ncbi.nlm.nih.gov/pubmed/19098912?dopt=Abstract)
  • Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Munz M, Gires O. Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009 Feb;11(2):162-71. doi: 10.1038/ncb1824. Epub 2009 Jan 11. (http://www.ncbi.nlm.nih.gov/pubmed/19136966?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4072)
  • Niessen RC, Hofstra RM, Westers H, Ligtenberg MJ, Kooi K, Jager PO, de Groote ML, Dijkhuizen T, Olderode-Berends MJ, Hollema H, Kleibeuker JH, Sijmons RH. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome. Genes Chromosomes Cancer. 2009 Aug;48(8):737-44. doi: 10.1002/gcc.20678. (http://www.ncbi.nlm.nih.gov/pubmed/19455606?dopt=Abstract)
  • OMIM: EPITHELIAL CELLULAR ADHESION MOLECULE (http://omim.org/entry/185535)
  • Schnell U, Kuipers J, Mueller JL, Veenstra-Algra A, Sivagnanam M, Giepmans BN. Absence of cell-surface EpCAM in congenital tufting enteropathy. Hum Mol Genet. 2013 Jul 1;22(13):2566-71. doi: 10.1093/hmg/ddt105. Epub 2013 Mar 5. (http://www.ncbi.nlm.nih.gov/pubmed/23462293?dopt=Abstract)
  • Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, Schork NJ, Lavine JE, Taylor S, Newbury RO, Kolodner RD, Hoffman HM. Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 2008 Aug;135(2):429-37. doi: 10.1053/j.gastro.2008.05.036. Epub 2008 May 15. (http://www.ncbi.nlm.nih.gov/pubmed/18572020?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: May 2013
Published: July 7, 2014