EPCAM
Chr 2ARADepithelial cell adhesion molecule
Also known as: Ber-Ep4, BerEp4, DIAR5, EGP-2, EGP314, EGP40, ESA, HNPCC8
The EPCAM protein functions as a homotypic calcium-independent cell adhesion molecule expressed on epithelial cells and may provide immunological barrier function between intestinal epithelial cells and intraepithelial lymphocytes. Mutations cause congenital tufting enteropathy with severe diarrhea presenting in infancy, inherited in an autosomal recessive pattern, and Lynch syndrome 8, inherited in an autosomal dominant pattern. The gene shows tolerance to loss-of-function variants (LOEUF 1.159), suggesting different pathogenic mechanisms may underlie these distinct clinical presentations.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 0 | 28 | 0 | 34 |
Likely Pathogenic | 4 | 0 | 7 | 0 | 11 |
VUS | 1 | 295 | 16 | 0 | 312 |
Likely Benign | 0 | 9 | 9 | 107 | 125 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 2 | |||
| Total | 11 | 304 | 60 | 107 | 484 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
EPCAM · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Videocapsule Endoscopy in Lynch Syndrome
RECRUITINGEvolutive and Functional Bases of Menstruation in Women - 2
RECRUITINGEC_ItaLynch: Mainstreaming the Diagnosis of Lynch Syndrome
NOT YET RECRUITINGPancreatic Cancer Early Detection Consortium
RECRUITINGUnveiling the Microbial Impact on Intestinal Fibrosis
NOT YET RECRUITINGPatient Centered Clinical Decision Support for Hereditary Cancer Syndromes
ENROLLING BY INVITATIONLynch Syndrome X-Talk of Enteral Mucosa With Immune System
RECRUITINGExoLuminate Study for Early Detection of Pancreatic Cancer
RECRUITINGThe Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment in Crohn's Disease
NOT YET RECRUITINGAnalysing Outcomes After Prostate Cancer Diagnosis and Treatment in Carriers of Rare Germline Mutations
RECRUITINGKPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
RECRUITINGCascade Testing in Families With Newly Diagnosed Hereditary Breast and Ovarian Cancer Syndrome
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools