EPCAM

epithelial cell adhesion molecule, the group of CD molecules|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:47345158-47387601

Previous symbols: [ "M4S1", "MIC18", "TACSTD1" ]

Links

ENSG00000119888 ∙ NCBI:4072 ∙ OMIM:185535 ∙ HGNC:11529 ∙ Uniprot:P16422 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital diarrhea 5 with tufting enteropathy (Definitive), mode of inheritance: AR
• Lynch syndrome 8 (Strong), mode of inheritance: AD
• congenital diarrhea 5 with tufting enteropathy (Strong), mode of inheritance: AR
• Lynch syndrome 8 (Definitive), mode of inheritance: AD
• congenital diarrhea 5 with tufting enteropathy (Definitive), mode of inheritance: AR
• Lynch syndrome (Supportive), mode of inheritance: AD
• congenital diarrhea 5 with tufting enteropathy (Supportive), mode of inheritance: AR
• Lynch syndrome 8 (Definitive), mode of inheritance: Mitochondrial
• Lynch syndrome (Definitive), mode of inheritance: AD
• hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD
• congenital diarrhea 5 with tufting enteropathy (Strong), mode of inheritance: AR
• Lynch syndrome 8 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Colorectal cancer, hereditary nonpolyposis, type 8 (Lynch syndrome 8); Diarrhea 5, with tufting enteropathy, congenital	AD/AR	Gastrointestinal; Oncologic	In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types, awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; In Diarrhea 5, with tufting enteropathy, congenital, most affected individuals require parenteral nutrition for normal growth and development, and awareness can allow prompt medical/nutritional support	Gastrointestinal; Musculoskeletal; Oncologic	100367; 8057225; 16951683; 18572020; 19820410; 19098912; 20388775; 20301390; 21309036; 21227399
Specific deletions result in MSH2 inactivation; Although Colorectal cancer, hereditary nonpolyposis, type 8 typically manifests in adulthood, individuals have been reported such that familial screening would be recommended to commence during the pediatric period; Diarrhea 5, with tufting enteropathy, congenital may include additional features, such as dysmorphism

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPCAM gene.

• Congenital diarrhea 5 with tufting enteropathy (6 variants)
• not provided (5 variants)
• Hereditary nonpolyposis colorectal neoplasms (5 variants)
• Gastric cancer (2 variants)
• Hereditary cancer-predisposing syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPCAM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				162		162
missense			317	16	5	338
nonsense	7	2				9
start loss		1				1
frameshift	3					3
inframe indel			6			6
splice donor/acceptor (+/-2bp)	3	3	4			10
splice region			7	13	2	22
non coding		1	5	36	34	76
Total	13	7	332	214	39

Highest pathogenic variant AF is 0.0000197

Variants in EPCAM

This is a list of pathogenic ClinVar variants found in the EPCAM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-47369005-C-G			Benign (Jun 15, 2019)
2-47369061-A-G			Likely benign (Jul 26, 2019)
2-47369259-G-C			Likely benign (Jun 22, 2019)
2-47369314-G-T		Lynch syndrome	Uncertain significance (Jun 14, 2016)
2-47369408-C-G			Likely benign (Jul 20, 2018)
2-47369427-C-T		Lynch syndrome	Uncertain significance (Jun 14, 2016)
2-47369450-GCCCTCCCGCGAGTCCCGGGC-G			Benign (Mar 03, 2015)
2-47369502-CAGCATGGCGCCCCCGCAGGTCCTCGCGTTCGGGCTTCTGCTTGCCGCGGCGACGGCGACTTTTGCCGCAGCTCAGGAAG-C		Lynch syndrome 8	Uncertain significance (-)
2-47369505-C-G		Lynch syndrome 8	not provided (-)
2-47369506-A-G		Gastric cancer • EPCAM-related disorder	Likely pathogenic (Aug 29, 2023)
2-47369508-G-C		Gastric cancer	Pathogenic (Jul 01, 2021)
2-47369510-C-T		not specified • Hereditary cancer-predisposing syndrome	Benign/Likely benign (Sep 01, 2023)
2-47369511-G-A		Hereditary cancer-predisposing syndrome	Likely benign (Feb 14, 2022)
2-47369511-G-C		Hereditary cancer-predisposing syndrome	Likely benign (Dec 25, 2023)
2-47369511-G-T		Hereditary cancer-predisposing syndrome • EPCAM-related disorder	Likely benign (Aug 10, 2023)
2-47369511-GC-G		Gastric cancer	Pathogenic (Jul 01, 2021)
2-47369512-C-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Jan 16, 2023)
2-47369512-C-T		Hereditary nonpolyposis colorectal neoplasms	Uncertain significance (Sep 02, 2021)
2-47369513-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Sep 16, 2023)
2-47369514-C-A		Hereditary cancer-predisposing syndrome	Likely benign (Jun 02, 2022)
2-47369514-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Aug 09, 2022)
2-47369516-C-G		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 27, 2022)
2-47369516-C-T		not specified • Congenital diarrhea 5 with tufting enteropathy;Lynch syndrome 8	Uncertain significance (Nov 24, 2021)
2-47369517-G-A		Hereditary cancer-predisposing syndrome	Likely benign (Oct 05, 2023)
2-47369517-G-T		Hereditary cancer-predisposing syndrome	Likely benign (Sep 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPCAM	protein_coding	protein_coding	ENST00000263735	9	42444

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.28e-7	0.596	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.43	219	167	1.31	0.00000827	2059
Missense in Polyphen		65	51.667	1.258		654
Synonymous	-1.65	75	58.9	1.27	0.00000311	580
Loss of Function	1.06	13	17.8	0.729	9.93e-7	212

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000438	0.000438
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.000360	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E. {ECO:0000269|PubMed:15195135, ECO:0000269|PubMed:15922867, ECO:0000269|PubMed:19785009, ECO:0000269|PubMed:20064925}.
• Disease: DISEASE: Diarrhea 5, with tufting enteropathy, congenital (DIAR5) [MIM:613217]: An intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum. {ECO:0000269|PubMed:18572020}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hereditary non-polyposis colorectal cancer 8 (HNPCC8) [MIM:613244]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269|PubMed:19098912}. Note=The disease is caused by mutations affecting the gene represented in this entry. HNPCC8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM.
• Pathway: Cell surface interactions at the vascular wall;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.295

Intolerance Scores

• loftool: 0.719
• rvis_EVS: 0.37
• rvis_percentile_EVS: 75.29

Haploinsufficiency Scores

• pHI: 0.615
• hipred: N
• hipred_score: 0.219
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.211

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Epcam
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: epcam
• Affected structure: keratinocyte
• Phenotype tag: abnormal
• Phenotype quality: aggregated

Gene ontology

• Biological process: ureteric bud development;positive regulation of cell population proliferation;signal transduction involved in regulation of gene expression;positive regulation of transcription by RNA polymerase II;stem cell differentiation;leukocyte migration;cell-cell adhesion;negative regulation of cell-cell adhesion mediated by cadherin;positive regulation of stem cell proliferation
• Cellular component: plasma membrane;bicellular tight junction;cell surface;integral component of membrane;basolateral plasma membrane;apical plasma membrane;lateral plasma membrane;extracellular exosome
• Molecular function: protein binding;protein-containing complex binding;cadherin binding involved in cell-cell adhesion