EPCAM (Epithelial Cell Adhesion Molecule): Gene, Function, and Clinical Significance
A comprehensive biomedical overview of the EPCAM gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | EPCAM |
|---|---|
| Full Name | Epithelial cell adhesion molecule |
| Gene Type | Protein coding |
| Chromosomal Location | 2p21 (GRCh38: 2:47,307,887-47,323,471) |
| NCBI Gene ID | 4072 ncbi.nlm.nih.gov/gene/4072 |
| Ensembl ID | ENSG00000119888 |
| UniProt ID | P16422 |
| OMIM ID | 185535 |
| HGNC ID | 11529 |
| Aliases | ESA, KSA, M4S1, MK-1, DIAR5, EGP-2, EGP314, EGP40, KS1/4, MIC18, TROP1, EGP, CD326, HNPCC8, BerEp4, GA733-2, Ly74, M1S2, TACSTD1 |
Description
EPCAM (Epithelial Cell Adhesion Molecule) encodes a transmembrane glycoprotein that mediates calcium-independent homotypic cell-cell adhesion in epithelial cells. It is expressed on the basolateral surface of most normal epithelial tissues and is frequently overexpressed in carcinomas. EPCAM also plays roles in cell signaling, migration, proliferation, and differentiation. Mutations in EPCAM are associated with congenital tufting enteropathy and Lynch syndrome (via epigenetic silencing of MSH2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lynch syndrome (HNPCC) | Deletion of 3' end of EPCAM causes hypermethylation of the MSH2 promoter, leading to MSH2 silencing and mismatch repair deficiency. | ClinVar, OMIM |
| Congenital tufting enteropathy | Biallelic loss-of-function mutations in EPCAM disrupt intestinal epithelial integrity, causing severe diarrhea and intestinal villous atrophy. | OMIM, UniProt |
| Colorectal cancer | Somatic mutations and overexpression of EPCAM contribute to tumor progression and metastasis; also implicated in therapy resistance. | COSMIC, NCBI |
| Pancreatic cancer | EPCAM overexpression is associated with poor prognosis and is a target for immunotherapy. | COSMIC, literature |
| Breast cancer | EPCAM is overexpressed in certain subtypes and may promote epithelial-mesenchymal transition. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | High (nTPM ~ 200) | High |
| Small intestine | High (nTPM ~ 180) | High |
| Liver | Medium (nTPM ~ 50) | Medium |
| Lung | Medium (nTPM ~ 40) | Medium |
| Kidney | Medium (nTPM ~ 30) | Medium |
| Brain | Low (nTPM < 10) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (colon) | High (nTPM ~ 300) | Colorectal adenocarcinoma cell line |
| HCT116 (colon) | Medium (nTPM ~ 150) | Colorectal carcinoma |
| MCF7 (breast) | Medium (nTPM ~ 100) | Breast adenocarcinoma |
| A549 (lung) | Low (nTPM ~ 20) | Lung carcinoma |
| HepG2 (liver) | Low (nTPM ~ 15) | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.499_500del (p.Lys167GlufsTer5) | Frameshift | Rare (in congenital tufting enteropathy) | Loss of function |
| c.556C>T (p.Arg186Ter) | Nonsense | Rare (in congenital tufting enteropathy) | Loss of function |
| 3' end deletions (e.g., exon 9 deletion) | Structural variant | Found in Lynch syndrome families | Loss of MSH2 expression via promoter methylation |
| Missense variants (e.g., p.Thr275Met) | Missense | Somatic, low frequency in cancers | Unknown; may affect adhesion |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., frameshift, nonsense) cause congenital tufting enteropathy due to loss of EPCAM protein, disrupting intestinal epithelial barrier.
Gain of Function (GOF)
Overexpression of wild-type EPCAM in cancers is considered a gain-of-function event, promoting cell proliferation, migration, and survival.
Dominant Negative (DN)
No clear dominant-negative mutations reported; however, some missense variants may interfere with protein function in a dominant manner, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • cell adhesion molecule binding |
| • identical protein binding | • calcium ion binding |
| • cell-cell adhesion | • epithelial cell differentiation |
| • positive regulation of cell migration | • positive regulation of cell proliferation |
| • signal transduction | • cell surface receptor signaling pathway |
Pathways
• Cell adhesion molecules (CAMs)
• Epithelial cell signaling in Helicobacter pylori infection
• Pathways in cancer
• Adherens junction
• Regulation of actin cytoskeleton
Protein Summary
EPCAM is a type I transmembrane glycoprotein of 314 amino acids (approx. 40 kDa) with an extracellular domain containing two EGF-like repeats and a thyroglobulin type A domain. It mediates homophilic calcium-independent cell adhesion. The protein is cleaved by proteases (e.g., TACE) to release soluble EPCAM, which can modulate signaling. Intracellularly, it interacts with claudins and other proteins to regulate tight junctions. EPCAM is also involved in Wnt signaling and is a cancer stem cell marker.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPCAM Knockout HEK293 Cell Line | EDJ-KQ17721 | Human | 4072 | Details Get a Quote |
| EPCAM Knockout HCT 116 Cell Line | EDJ-KQ18462 | Human | 4072 | Details Get a Quote |
| EPCAM Knockout A-549 Cell Line | EDJ-KQ19793 | Human | 4072 | Details Get a Quote |
| EPCAM Knockout HeLa Cell Line | EDJ-KQ19795 | Human | 4072 | Details Get a Quote |
| EPCAM (p.M115T) Point Mutation in HAP1 Cell Line | EDC03460 | Human | 4072 | Details Get a Quote |
| Epcam Overexpression ID8 Stable Cell Line | EDC01480 | Mouse | 17075 | Details Get a Quote |
| Epcam Overexpression 4T1 Stable Cell Line | EDC01481 | Mouse | 17075 | Details Get a Quote |
| Epcam Overexpression CT26.WT Stable Cell Line | EDC01482 | Mouse | 17075 | Details Get a Quote |
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