EPCAM

Chr 2ARAD

epithelial cell adhesion molecule

Also known as: Ber-Ep4, BerEp4, DIAR5, EGP-2, EGP314, EGP40, ESA, HNPCC8

NCBI Gene: 4072 ENSG00000119888 UniProt: P16422 OMIM: 185535

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. Mutations in this gene result in congenital tufting enteropathy. [provided by RefSeq, Dec 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Diarrhea 5, with tufting enteropathy, congenitalMIM #613217

Lynch syndrome 8MIM #613244

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

637

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — EPCAM

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 1.06

OE 0.73 (0.47–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.43Z-score

OE missense 1.31 (1.17–1.47)

219 obs / 167.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.47–1.16)

0≤0.351.4

Missense OE?1.31 (1.17–1.47)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 13 / 17.8Missense obs/exp: 219 / 167.0Syn Z: -1.65

Background carrier burden — how many people carry a rare variant somewhere in EPCAM?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

852 rare PASS variants

Rare truncating (LoF)

1 in 580

165 rare PASS variants

Rare synonymous (reference)

1 in 150

288 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EPCAM. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 430
South Asian	~43k	1 in 58	1 in 350
Remaining (unassigned)	~30k	1 in 53	1 in 450
European (Finnish)	~27k	1 in 260	1 in 1,400
Admixed American	~22k	1 in 78	1 in 330
African / African American	~21k	1 in 62	1 in 220
East Asian	~20k	1 in 64	1 in 340
Ashkenazi Jewish	~13k	1 in 270	1 in 550
Middle Eastern	~2,884	1 in 68	1 in 270

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 9 coding exons well covered in gnomAD exomes; exons 5, 6, 9 marginal. Genomes: all 9.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — EPCAM

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Colorectal CancerAdenoma ColonAdenoma Colon Polyp

Liquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection

RECRUITING

NCT07450612San Raffaele UniversityStarted 2024-01-01

BEACON

Lynch Syndrome

Lynch Syndrome Integrative Epidemiology and Genetics

RECRUITING

NCT06582914University of Colorado, DenverStarted 2024-10-01

Lynch SyndromeEndometrial Cancer

EC_ItaLynch: Mainstreaming the Diagnosis of Lynch Syndrome

NOT YET RECRUITING

NCT06501417Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2024-08-01

mainstreaming

Pancreas CancerPeutz-Jeghers Syndrome (PJS)Gene Mutation

The Cancer of the Pancreas Screening-5 CAPS5)Study

RECRUITING

NCT02000089Phase PHASE3Johns Hopkins UniversityStarted 2014-01-06

SecretinMRITumor marker gene test with CA19-9

Lynch SyndromeLynch Syndrome ILynch Syndrome II

Lynch Syndrome X-Talk of Enteral Mucosa With Immune System

RECRUITING

NCT06708429San Raffaele UniversityStarted 2023-06-01

LYNX EYE (Lynch syndrome X-Talk of Enteral mucosa with Immune System)

BRCA1 MutationPOLD1 Gene MutationCDKN2A Mutation

An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results

RECRUITING

NCT05420064Phase NAMemorial Sloan Kettering Cancer CenterStarted 2022-12-01

Intervention Arm At-risk Relative/ARR ContactsMyGene PortalStandard of Care

Hereditary Breast/Ovarian Cancer (brca1, brca2)Lynch SyndromeGenetic Variation

Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes

ENROLLING BY INVITATION

NCT06914726Phase NAHealthPartners InstituteStarted 2025-07-09

Patient Centered Clinical Decision Support (PC-CDS)

BRCA-Mutated Ovarian CarcinomaBRIP1 Gene MutationMSH2 A636P

Cascade Testing in Families With Newly Diagnosed Hereditary Breast and Ovarian Cancer Syndrome

ACTIVE NOT RECRUITING

NCT04009148NYU Langone HealthStarted 2019-03-01