EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome

Hum Mutat. 2019 Feb;40(2):142-161. doi: 10.1002/humu.23688. Epub 2018 Nov 29.


The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3' end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype-phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome.

Keywords: EPCAM; Lynch syndrome; congenital tufting enteropathy; genotype-phenotype correlation; in silico simulation; protein modeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Diarrhea, Infantile / genetics*
  • Diarrhea, Infantile / pathology
  • Epithelial Cell Adhesion Molecule / chemistry*
  • Epithelial Cell Adhesion Molecule / genetics
  • Epithelial Cells / metabolism
  • Genetic Association Studies
  • Humans
  • Malabsorption Syndromes / genetics*
  • Malabsorption Syndromes / pathology
  • Models, Molecular*
  • MutS Homolog 2 Protein / genetics
  • Mutation, Missense / genetics
  • RNA Splice Sites / genetics


  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • RNA Splice Sites
  • MSH2 protein, human
  • MutS Homolog 2 Protein

Supplementary concepts

  • Diarrhea 5, With Tufting Enteropathy, Congenital