EPCAM

Summary

EPCAM (epithelial cell adhesion molecule, HGNC:11529) is a protein-coding gene on chromosome 2p21, encoding Epithelial cell adhesion molecule (P16422). 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.

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.

Source: NCBI Gene 4072 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lynch syndrome (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,142 total — 120 pathogenic, 19 likely-pathogenic (top 2% of genes corpus-wide)
• GTEx eGene: eQTL in 40 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 97
• Drug target: yes — 10 curated mechanism-of-action drugs
• Approved drugs (ChEMBL mechanism of action): 1 — Catumaxomab
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.34 (unconstrained)
• MANE Select transcript: NM_002354
• Interaction hub: 3,638 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11529
Approved symbol	EPCAM
Name	epithelial cell adhesion molecule
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	Ly74, TROP1, GA733-2, EGP34, EGP40, EGP-2, KSA, CD326, Ep-CAM, HEA125, KS1/4, MK-1, MH99, MOC31, MOC-31, 323/A3, 17-1A, TACST-1, CO-17A, ESA, BerEp4, Ber-Ep4
Ensembl gene	ENSG00000119888
Ensembl biotype	protein_coding
OMIM	185535
Entrez	4072

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 7 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000263735

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 2, TSL 5: 3

ENST00000263735, ENST00000405271, ENST00000419334, ENST00000456133, ENST00000474691, ENST00000490733, ENST00000895681, ENST00000895682, ENST00000895683, ENST00000895684, ENST00000895685, ENST00000934495, ENST00000934496, ENST00000983074, ENST00000983075, ENST00001050079, ENST00001050081, ENST00001079082, ENST00001079083, ENST00001079084, ENST00001120478, ENST00001120479, ENST00001143609

RefSeq mRNA: 1 — MANE Select: NM_002354 NM_002354

CCDS: CCDS1833

Canonical transcript exons

ENST00000263735 — 9 exons

Exon	Start	End
ENSE00000809826	47373808	47374048
ENSE00000962738	47373463	47373570
ENSE00001069309	47369311	47369581
ENSE00001683862	47386572	47387020
ENSE00003480953	47378953	47379054
ENSE00003513916	47385166	47385210
ENSE00003552250	47375234	47375299
ENSE00003560359	47379769	47379969
ENSE00003643653	47377014	47377077

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 62.4018 / max 2406.5364, expressed in 822 samples.

Highest expression (Bgee): jejunal mucosa, colonic mucosa, mucosa of sigmoid colon, rectum, duodenum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EPCAM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 40 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Heart Left Ventricle	eqtl	1.5e-38	+1.40	2:47369714:C:CG
Brain Cerebellar Hemisphere	eqtl	4.9e-34	+1.61	2:47369714:C:CG
Brain Frontal Cortex BA9	eqtl	2.0e-33	+1.63	2:47369714:C:CG
Adipose Subcutaneous	eqtl	4.5e-31	+0.89	2:47369714:C:CG
Esophagus Muscularis	eqtl	5.1e-31	+1.17	2:47369714:C:CG
Brain Hypothalamus	eqtl	4.0e-30	+0.90	2:47369714:C:CG
Brain Cortex	eqtl	4.8e-29	+1.52	2:47369714:C:CG
Brain Cerebellum	eqtl	6.2e-29	+1.73	2:47369714:C:CG
Esophagus Gastroesophageal Junction	eqtl	1.3e-28	+1.26	2:47369714:C:CG
Brain Spinal cord cervical c-1	eqtl	1.6e-26	+1.44	2:47369714:C:CG
Heart Atrial Appendage	eqtl	3.9e-26	+1.28	2:47369714:C:CG
Nerve Tibial	eqtl	2.4e-25	+0.78	2:47369714:C:CG
Brain Anterior cingulate cortex BA24	eqtl	3.0e-25	+1.31	2:47369714:C:CG
Adipose Visceral Omentum	eqtl	3.1e-23	+0.97	2:47369714:C:CG
Brain Caudate basal ganglia	eqtl	3.9e-22	+0.47	2:47369714:C:CG
Brain Hippocampus	eqtl	4.2e-20	+0.92	2:47369714:C:CG
Thyroid	eqtl	1.8e-18	+0.28	2:47369714:C:CG
Spleen	eqtl	3.2e-18	+1.01	2:47369714:C:CG
Brain Nucleus accumbens basal ganglia	eqtl	5.7e-18	+0.70	2:47369714:C:CG
Brain Substantia nigra	eqtl	1.1e-17	+1.24	2:47369714:C:CG

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
20151	56.5318	715
20148	2.2678	558
20152	1.0614	437
20153	0.9200	439
20155	0.5506	257
20150	0.2934	188
20156	0.2070	105
20154	0.2049	101
20149	0.1865	124
20147	0.0889	36

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.94	gold quality
colonic mucosa	UBERON:0000317	99.84	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.83	gold quality
rectum	UBERON:0001052	99.76	gold quality
duodenum	UBERON:0002114	99.73	gold quality
mucosa of transverse colon	UBERON:0004991	99.67	gold quality
renal medulla	UBERON:0000362	99.53	gold quality
corpus epididymis	UBERON:0004359	99.52	gold quality
islet of Langerhans	UBERON:0000006	99.46	gold quality
bronchial epithelial cell	CL:0002328	99.43	gold quality
epithelial cell of pancreas	CL:0000083	99.26	gold quality
caput epididymis	UBERON:0004358	99.26	gold quality
ileal mucosa	UBERON:0000331	99.17	gold quality
epithelium of bronchus	UBERON:0002031	99.07	gold quality
nephron tubule	UBERON:0001231	99.06	gold quality
bronchus	UBERON:0002185	99.00	gold quality
pancreatic ductal cell	CL:0002079	98.96	gold quality
left lobe of thyroid gland	UBERON:0001120	98.87	gold quality
thyroid gland	UBERON:0002046	98.84	gold quality
right lobe of thyroid gland	UBERON:0001119	98.68	gold quality
body of pancreas	UBERON:0001150	98.60	gold quality
pancreas	UBERON:0001264	98.52	gold quality
metanephros cortex	UBERON:0010533	98.34	gold quality
pylorus	UBERON:0001166	98.33	gold quality
epithelium of nasopharynx	UBERON:0001951	98.33	gold quality
gall bladder	UBERON:0002110	98.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.26	gold quality
secondary oocyte	CL:0000655	98.23	gold quality
seminal vesicle	UBERON:0000998	98.22	gold quality
right uterine tube	UBERON:0001302	98.15	gold quality
endometrium epithelium	UBERON:0004811	98.09	gold quality
lower lobe of lung	UBERON:0008949	98.03	gold quality
adult mammalian kidney	UBERON:0000082	98.02	gold quality
type B pancreatic cell	CL:0000169	97.96	gold quality
visceral pleura	UBERON:0002401	97.85	gold quality
vermiform appendix	UBERON:0001154	97.84	gold quality
parotid gland	UBERON:0001831	97.75	gold quality
kidney	UBERON:0002113	97.69	gold quality
caecum	UBERON:0001153	97.67	gold quality
palpebral conjunctiva	UBERON:0001812	97.61	gold quality
nasal cavity mucosa	UBERON:0001826	97.51	gold quality
oocyte	CL:0000023	97.47	gold quality
nasal cavity epithelium	UBERON:0005384	97.11	gold quality
epithelium of mammary gland	UBERON:0003244	97.04	gold quality
endometrium	UBERON:0001295	96.97	gold quality
mammary duct	UBERON:0001765	96.93	gold quality
kidney epithelium	UBERON:0004819	96.80	gold quality
pituitary gland	UBERON:0000007	96.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.28	gold quality
adult organism	UBERON:0007023	96.28	gold quality
amniotic fluid	UBERON:0000173	96.25	gold quality
cauda epididymis	UBERON:0004360	96.07	gold quality
lung	UBERON:0002048	95.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.76	gold quality
metanephros	UBERON:0000081	95.53	gold quality
saliva-secreting gland	UBERON:0001044	95.43	gold quality
adenohypophysis	UBERON:0002196	95.27	gold quality
cortex of kidney	UBERON:0001225	95.25	gold quality
trachea	UBERON:0003126	95.20	gold quality
small intestine	UBERON:0002108	94.86	gold quality
upper lobe of lung	UBERON:0008948	94.76	gold quality
minor salivary gland	UBERON:0001830	94.72	gold quality
renal glomerulus	UBERON:0000074	94.54	gold quality
esophagus squamous epithelium	UBERON:0006920	94.50	gold quality
upper lobe of left lung	UBERON:0008952	94.49	gold quality
right lung	UBERON:0002167	94.42	gold quality
transverse colon	UBERON:0001157	94.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.59	gold quality
mouth mucosa	UBERON:0003729	93.59	gold quality
metanephric glomerulus	UBERON:0004736	93.51	gold quality
cardia of stomach	UBERON:0001162	92.74	gold quality
germinal epithelium of ovary	UBERON:0001304	92.30	gold quality
epithelium of esophagus	UBERON:0001976	92.21	gold quality
urethra	UBERON:0000057	92.05	gold quality
mammary gland	UBERON:0001911	91.37	gold quality
eye	UBERON:0000970	91.28	gold quality
thoracic mammary gland	UBERON:0005200	91.26	gold quality
colonic epithelium	UBERON:0000397	90.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.63	gold quality
prostate gland	UBERON:0002367	89.72	gold quality
intestine	UBERON:0000160	89.71	gold quality
stomach	UBERON:0000945	89.65	gold quality
jejunum	UBERON:0002115	89.57	gold quality
body of stomach	UBERON:0001161	88.89	gold quality
large intestine	UBERON:0000059	87.77	gold quality
mucosa of urinary bladder	UBERON:0001259	87.57	gold quality
fallopian tube	UBERON:0003889	87.41	gold quality
squamous epithelium	UBERON:0006914	87.31	gold quality
colon	UBERON:0001155	87.21	gold quality
adrenal tissue	UBERON:0018303	86.88	gold quality
oviduct epithelium	UBERON:0004804	86.24	gold quality
upper leg skin	UBERON:0004262	86.06	gold quality
testis	UBERON:0000473	85.76	gold quality
sperm	CL:0000019	85.39	gold quality
gingiva	UBERON:0001828	85.36	gold quality
right testis	UBERON:0004534	85.20	gold quality
oral cavity	UBERON:0000167	85.08	gold quality
fundus of stomach	UBERON:0001160	85.06	gold quality
male germ cell	CL:0000015	84.61	gold quality
right adrenal gland cortex	UBERON:0035827	84.57	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	2378.52
E-CURD-46	yes	1473.62
E-GEOD-124472	yes	1434.74
E-CURD-88	yes	1426.53
E-CURD-53	yes	1123.40
E-MTAB-9388	yes	1040.45
E-MTAB-10485	yes	1021.18
E-MTAB-9154	yes	935.90
E-GEOD-114530	yes	907.53
E-CURD-114	yes	818.92
E-MTAB-10662	yes	814.20
E-HCAD-10	yes	802.45
E-MTAB-10287	yes	739.11
E-MTAB-8205	yes	437.33
E-MTAB-10042	yes	381.22

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Colon	tissue	756.2	high
Small intestine	tissue	725.1	high
Rectum	tissue	705.8	high
Duodenum	tissue	684.4	high
Thyroid gland	tissue	268.9	medium
Epididymis	tissue	225.6	high
Kidney	tissue	208.5	high
Parathyroid gland	tissue	206.4	high
Stomach 1	tissue	162.8	not detected
Salivary gland	tissue	113.0	not detected
Cervix	tissue	109.4	low
Pancreas	tissue	109.4	low
Fallopian tube	tissue	107.6	high
Breast	tissue	93.3	low
Pituitary gland	tissue	92.0
Appendix	tissue	72.7	high
Lung	tissue	70.5	low
Gallbladder	tissue	66.7	high
Prostate	tissue	56.9	not detected
Seminal vesicle	tissue	49.8	high
Endometrium 1	tissue	30.9	medium
Urinary bladder	tissue	28.9	not detected
Smooth muscle	tissue	20.7	not detected
Testis	tissue	20.3	medium
Adrenal gland	tissue	11.5	not detected
Amygdala	tissue	9.8
Bone marrow	tissue	9.6	not detected
Hippocampal formation	tissue	9.5
Cerebral cortex	tissue	8.3	not detected
Temporal cortex	tissue	8.3
Olfactory bulb	tissue	7.7
Cerebellum	tissue	7.3	not detected
Nucleus accumbens	tissue	7.0
Ventral forebrain	tissue	7.0
Basal ganglia	tissue	6.5	not detected
Insular cortex	tissue	6.5
Septum	tissue	6.2
Entorhinal cortex	tissue	6.1
Putamen	tissue	6.0
Corpus callosum	tissue	6.0
Thymus	tissue	5.9
Retrosplenial and cingulate cortex	tissue	5.9
Retrosplenial cortex	tissue	5.9
Prefrontal cortex	tissue	5.7
Thalamus	tissue	5.7
Hypothalamus	tissue	5.7
Locus coeruleus	tissue	5.7
Motor cortex	tissue	5.4
Superior colliculi	tissue	5.0
Spinal cord	tissue	5.0
Periaqueductal gray	tissue	5.0
Esophagus	tissue	4.9	not detected
Midbrain	tissue	4.9
Substantia nigra	tissue	4.8
Occipital cortex	tissue	4.8
Vagina	tissue	4.6	not detected
Somatosensory cortex	tissue	4.6
Medulla oblongata	tissue	4.3
Adipose tissue	tissue	4.2	not detected
Pons	tissue	3.8

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Ventromedial nucleus (18.3), Arcuate nucleus (17.1), Subiculum (9.5), Paraventricular nucleus (9.1), Lateral hypothalamic area (7.3).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets:

Target	Regulation
CCNA2	Activation
CCNE1	Activation
FABP5	Activation
MYC	Activation

Upstream regulators (CollecTRI, top): AR, CTNNB1, DNMT1, DNMT3A, FOXA2, HDAC1, HOXA10, KLF4, NANOG, NFKB1, NFKB, NFKBID, RELA, SALL4, TCF7L2, TP53, ZEB1, ZKSCAN7

miRNA regulators (miRDB)

Targeting EPCAM by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 52 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-6828-5P	99.31	69.21	1433

Functional genomics

gnomAD constraint: pLI 4.23e-06, LOEUF 1.34, missense Z -1.96 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000263735 — one region, missense o/e 1.32.

Literature-anchored findings (GeneRIF, showing 40)

• Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival. (PMID:12592372)
• amplification is induced by mutations in TP53 (PMID:12642870)
• A 1100 bp fragment of the EpCAM promoter containing the 570 bp fragment and additional 550 bp upstream has been cloned (PMID:12926061)
• Human EGP-2 antigen on epithelial cells of transgenic trachea transplants induces specific humoral and cellular immune responses, leading to mild form of obliterative airway disease. (egp-2) (PMID:14557747)
• Epithelial cell adhesion molecule has a role in progression of renal cell carcinoma but is absent in clear cell carcinoma (PMID:15102668)
• Ep-CAM antigen represents an attractive target for specific therapies with monoclonal antibodies or specific vaccines in patients with Ep-CAM-overexpressing gallbladder carcinoma. (PMID:15131054)
• EpCAM up-regulates c-myc and induces cell proliferation (PMID:15195135)
• up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of epithelial ovarian cancer (PMID:15240533)
• Vaccination with Ep-CAM protein may warrant further investigation as a novel therapeutic approach to colorectal cancer. (PMID:15328177)
• EpCAM is vastly expressed in retinoblastoma; EpCAM reactivity was significantly higher in the invasive than the noninvasive tumors and in poorly differentiated than in well-differentiated tumors (PMID:15557427)
• Ep-CAM was distributed differently in normal and various malignant colon tissues. MAbs against Ep-CAM may have diagnostic and therapeutic value to various colon carcinomas. (PMID:15637741)
• EpCAM shown to be signal transducing membrane protein involved in carcinogenesis via its ability to induce genes involved in cellular metabolism and proliferation (PMID:15922867)
• EpCAM expression in blood and primary and metastatic tumors is transient and dependent upon the local micro-environment (PMID:15942643)
• The carcinoma-specific epithelial glycoprotein-2 promoter controls efficient and selective gene expression in an adenoviral context. (PMID:16096650)
• MK-1 expression was found in 61% of samples. (PMID:16616808)
• Tumor-specific EpCAM expression and release into the circulation may serve as effective immunotherapy in esophageal cancer patients. (PMID:17143526)
• downregulation of EGP-2 promoter activity using zinc finger protein transcription factors may result in a novel anti-cancer treatment. (PMID:17186549)
• claudin-7-associated EpCAM is recruited into (tetraspanin-enriched membrane microdomains) and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation (PMID:17579117)
• analysis of EpCAM expression in normal, non-pathological tissues (PMID:17981779)
• EpCAM is a Wnt-beta-catenin signaling target gene (PMID:18006828)
• The spatiotemporal expression pattern of EpCAM changes during nephrogenesis (PMID:18025791)
• EpCAM expression in gallbladder tumors may serve as a prognostic factor for poor survival. (PMID:18285265)
• EpCAM and alpha-fetoprotein are expressed in hepatocellular carcinoma (PMID:18316609)
• Active DNA methylation leads to sustained silencing of endogenous EpCAM expression. (PMID:18398839)
• Perspectives for EpCAM-targeted apoptosis induction in cancer by EpCAM-selective bispecific antibodies. [REVIEW} (PMID:18508568)
• EpCAM is strongly over-expressed in a variety of carcinomas; mutants of EpCAM that substitute asparagine198 for alanine show a decreased expression and half-life at the plasma membrane. (PMID:18508581)
• Mutations in the gene for EpCAM are responsible for congenital tufting enteropathy. (PMID:18572020)
• Reduced expression of EpCAM and villin is associated withn Barrett’s adenocarcinoma and expression of EpCam and villin differs only between squamous epithelium and Barrett esophagus (PMID:18688077)
• unmethylation of the EpCAM promoter region was associated with EpCAM overexpression; however, it was not responsible for EpCAM overexpression by itself. (PMID:18949402)
• These data suggest that EpCAM is involved in signal transduction triggering several intracellular signalling pathways using tumor cell lines in colorectal and lung cancer. (PMID:19002182)
• the transcripts upregulated according to disease progression were associated with signaling pathway/transcription, including tumor-associated calcium signal transducer 1 and chemokine ligand 19, and with cell communication, such as collagen. (PMID:19012040)
• Ep-CAM was present in urothelial cell carcinoma in situ (CIS) of the bladder with a heterogeneous staining pattern. (PMID:19019843)
• EpCAM (TACSTD1) gene mutations occur in Lynch Syndrome and result in methylation of the 3’ located msh2 gene, which is involved in mismatch repair. (PMID:19098912)
• Patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM, are described. (PMID:19098912)
• EpCAM is frequently over-expressed on cancer initiating cells in various tumour entities (PMID:19132011)
• EpCAM signals to the cell nucleus following regulated intramembrane proteolysis and nuclear translocation of its intracellular domain (EpICD). EpICD on its own (26aa) is highly tumourigenic in SCID mice. (PMID:19136966)
• Here we show that regulated intramembrane proteolysis activates EpCAM as a mitogenic signal transducer in vitro and in vivo. (PMID:19136966)
• Data are the first demonstration that wild-type p53 protein binds to a response element within the EpCAM gene and negatively regulates EpCAM expression, and transcriptional repression of EpCAM contributes to p53 control of breast cancer invasion. (PMID:19141643)
• hepatocellular carcinoma growth and invasiveness is dictated by a subset of EpCAM(+) cells (PMID:19150350)
• the overexpression of epithelial cell adhesion molecule and reduced expression of E-cadherin in combination is more significant than a single marker for predicting poor survival. (PMID:19157508)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	epcam	ENSDARG00000040534
mus_musculus	Epcam	ENSMUSG00000045394
rattus_norvegicus	Epcam	ENSRNOG00000015667

Paralogs (1): TACSTD2 (ENSG00000184292)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:106653) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 37 distinct phenotype terms.

Mouse phenotype (MP)	Records
postnatal growth retardation	3
abnormal intestine physiology	3
abnormal intestine morphology	2
abnormal intestinal mucosa morphology	2
postnatal lethality, complete penetrance	2
abnormal enterocyte morphology	1
abnormal intestinal epithelium morphology	1
abnormal crypts of Lieberkuhn morphology	1
abnormal colon morphology	1
decreased body size	1
internal hemorrhage	1
decreased embryo size	1
decreased trophoblast giant cell number	1
abnormal placenta labyrinth morphology	1
embryonic growth arrest	1
abnormal ileum morphology	1
delayed neural tube closure	1
abnormal cell migration	1
abnormal duodenum morphology	1
intestinal edema	1
small intestinal inflammation	1
abnormal neural tube closure	1
abnormal jejunum morphology	1
small placenta	1
diarrhea	1

+12 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	Q1WER1	92.7%	Diamond
Bos taurus	Q3T0L5	85.4%	Diamond
Sus scrofa	Q75QW1	85.4%	Diamond
Gallus gallus	Q5F381	60.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
STPG4	protein-coding	285051
BCYRN1	ncRNA	618
MIR559	ncRNA	693144
CALM2	protein-coding	805
EPCAM-DT	ncRNA	101927043
MSH2	protein-coding	4436
KCNK12	protein-coding	56660
MSH2-OT1	ncRNA	644093

Protein

Protein identifiers

Epithelial cell adhesion molecule — P16422 (reviewed: P16422)

Alternative names: Adenocarcinoma-associated antigen, Cell surface glycoprotein Trop-1, Epithelial cell surface antigen, Epithelial glycoprotein, Epithelial glycoprotein 314, KS 1/4 antigen, KSA, Major gastrointestinal tumor-associated protein GA733-2, Tumor-associated calcium signal transducer 1

All UniProt accessions (3): B5MCA4, C9JKY3, P16422

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Monomer. Interacts with phosphorylated CLDN7.

Subcellular location. Lateral cell membrane. Cell junction. Tight junction.

Tissue specificity. Highly and selectively expressed by undifferentiated rather than differentiated embryonic stem cells (ESC). Levels rapidly diminish as soon as ESC’s differentiate (at protein levels). Expressed in almost all epithelial cell membranes but not on mesodermal or neural cell membranes. Found on the surface of adenocarcinoma.

Post-translational modifications. Hyperglycosylated in carcinoma tissue as compared with autologous normal epithelia. Glycosylation at Asn-198 is crucial for protein stability.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Lynch syndrome 8 (LYNCH8) [MIM:613244] A form of Lynch syndrome, 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. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it 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 Lynch syndrome 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 Lynch syndrome’ or ‘incomplete Lynch syndrome’ 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. The disease is caused by variants affecting the gene represented in this entry. LYNCH8 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.

Similarity. Belongs to the EPCAM family.

RefSeq proteins (1): NP_002345* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily
IPR041630	EpCAM_N	Domain
IPR043406	EPCAM/Trop-2	Family
IPR049420	EPCAM-Trop-2_C	Domain

Pfam: PF00086, PF18635, PF21283

Enzyme classification (BRENDA)

• EC 2.4.1.37 — fucosylgalactoside 3-alpha-galactosyltransferase (BRENDA: 12 organisms, 84 substrates, 31 inhibitors, 90 Km, 49 kcat entries)
• EC 2.4.1.40 — glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase (BRENDA: 12 organisms, 33 substrates, 15 inhibitors, 33 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

48 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GALACTOSE	0.01–4.5	17
UDP-ALPHA-D-GALACTOSE	0.023–0.78	11
ALPHA-FUC-(1->2)-BETA-D-GAL-(CH2)7CH3	0.088–2.64	8
BETA-D-GALACTOSYL-(1->4)-BETA-D-GLUCOSYL-(1<->1)	0.032–0.35	6
L-FUCOSYL-ALPHA-1,2-BETA-D-GALACTOSYL-O(CH2)7CH3	0.022–0.281	6
ALPHA-FUC-(1->2)-BETA-D-GAL-(CH2)7CH3	0.0099–0.4	6
UDP-N-ACETYL-ALPHA-D-GALACTOSAMINE	0.0087–0.086	6
UDP-GALNAC	0.0099–3.74	5
L-FUCOSYL-ALPHA-1,2-BETA-GALACTOSYL-O(CH2)7CH3	0.027–0.116	4
UDP-GLUCOSE	0.12–0.238	4
L-FUCOSYL-ALPHA-1,2-BETA-GALACTOSYL-O(CH2)7CH3	0.0087–0.167	4
UDP-GALNAC	0.023–0.78	3
UDP-N-ACETYLGALACTOSAMINE	0.285–0.34	3
2’-FUCOSYLLACTOSE	0.27–0.47	3
2’-FUCOSYLLACTOSE	0.08–0.5	2

UniProt features (52 total): strand 12, helix 10, sequence variant 7, disulfide bond 6, mutagenesis site 3, turn 3, glycosylation site 3, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
4MZV	Crystal structure of extracellular part of human EpCAM	X-RAY DIFFRACTION	1.86
6I07	Crystal structure of EpCAM in complex with scFv	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16422-F1	87.71	0.66

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 6I07

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (6)

Type	Positions
Disulfide bond	29–59, 38–48, 66–99, 110–116, 118–135, 27–46

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	74, 111, 198

Mutagenesis-validated functional residues (3)

Position	Phenotype
74	changed glycosylation pattern. complete loss of glycosylation and substantial decrease in protein expression; when associated with a-111 …
111	changed glycosylation pattern. complete loss of glycosylation and substantial decrease in protein expression; when associated with a-74 and …
198	decreased glycosylation, reduced protein stability and significant decrease in protein expression. complete loss of glycosylation and …

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 16; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-9638630	Attachment of bacteria to epithelial cells ⚕	curated
R-HSA-202733	Cell surface interactions at the vascular wall	curated
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells	curated
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells	curated
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells	curated
R-HSA-9938206	Developmental Lineage of Mammary Stem Cells	curated
R-HSA-9824439	Bacterial Infection Pathways ⚕	—
R-HSA-9931953	Biofilm formation ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9640148	Infection with Enterobacteria ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9734767	Developmental Cell Lineages	—
R-HSA-9734779	Developmental Cell Lineages of the Integumentary System	—
R-HSA-9924644	Developmental Lineages of the Mammary Gland	—
R-HSA-109582	Hemostasis	—

MSigDB gene sets: 480 (showing top): MODULE_52, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_CELL_ADHESION_MEDIATED_BY_CADHERIN, AREB6_03, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, GOBP_STEM_CELL_PROLIFERATION, GOBP_CELL_CELL_ADHESION, MODULE_118, BROWNE_HCMV_INFECTION_24HR_UP, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, CAFFAREL_RESPONSE_TO_THC_8HR_3_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6

GO Biological Process (8): ureteric bud development (GO:0001657), positive regulation of cell population proliferation (GO:0008284), signal transduction involved in regulation of gene expression (GO:0023019), positive regulation of transcription by RNA polymerase II (GO:0045944), stem cell differentiation (GO:0048863), negative regulation of cell-cell adhesion mediated by cadherin (GO:2000048), positive regulation of stem cell proliferation (GO:2000648), cell-cell adhesion (GO:0098609)

GO Molecular Function (3): protein-containing complex binding (GO:0044877), cadherin binding involved in cell-cell adhesion (GO:0098641), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cell surface (GO:0009986), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

10 top-level categories:

Category	Pathways
Developmental Lineages of the Mammary Gland	4
Hemostasis	1
Biofilm formation	1
Disease	1
Bacterial Infection Pathways	1
Developmental Biology	1
Developmental Cell Lineages	1
Infectious disease	1
Developmental Cell Lineages of the Integumentary System	1
Infection with Enterobacteria	1

GO top-level categories

31 GO namespaces:

Category	Terms
cellular anatomical structure	3
binding	2
plasma membrane region	2
mesonephric tubule development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
signal transduction	1
regulation of gene expression	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cell differentiation	1
negative regulation of cell-cell adhesion	1
cell-cell adhesion mediated by cadherin	1
regulation of cell-cell adhesion mediated by cadherin	1
positive regulation of cell population proliferation	1
stem cell proliferation	1
regulation of stem cell proliferation	1
cell adhesion	1
cadherin binding	1
cell-cell adhesion	1
cell-cell adhesion mediator activity	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
basal plasma membrane	1
apical part of cell	1
plasma membrane	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of cell-cell adhesion mediated by cadherin	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of stem cell proliferation	BP	mutant phenotype
positive regulation of transcription by RNA polymerase II	BP	direct assay
signal transduction involved in regulation of gene expression	BP	mutant phenotype
stem cell differentiation	BP	mutant phenotype
apical plasma membrane	CC	direct assay
basolateral plasma membrane	CC	direct assay
bicellular tight junction	CC	direct assay
extracellular exosome	CC	high-throughput assay
lateral plasma membrane	CC	direct assay
plasma membrane	CC	direct assay
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,638 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPCAM	MSH2	P43246	906
EPCAM	MSH6	P52701	877
EPCAM	PMS2	P54278	864
EPCAM	PTPRC	P08575	857
EPCAM	MLH1	P40692	852
EPCAM	SPINT2	O43291	818
EPCAM	CD44	P16070	814
EPCAM	CD24	P25063	805
EPCAM	PROM1	O43490	804
EPCAM	KRT19	P08727	793
EPCAM	KRT8	P05787	754
EPCAM	CDH1	P12830	752
EPCAM	ERBB2	P04626	746
EPCAM	PECAM1	P16284	745
EPCAM	MUC1	P13931	719

IntAct

Human interaction partners of EPCAM in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
CALR	physical association	0.560	3
CDH1	physical association	0.560	3
CDK5R1	physical association	0.560	3
DLST	physical association	0.560	3
NEK7	physical association	0.560	3

BioGRID (48 interactions; top human partners by supporting records): CFTR (Affinity Capture-MS; 2 records), CLEC4D (Affinity Capture-MS; 2 records), MARCH8 (Affinity Capture-Western; 2 records), TMPRSS4 (Affinity Capture-MS; 2 records), ALDOA (Cross-Linking-MS (XL-MS)), BCAP31 (Affinity Capture-Western), BSG (Proximity Label-MS), CLDN7 (Affinity Capture-MS), DDR2 (Proximity Label-MS), DUSP4 (Affinity Capture-MS), EEA1 (Cross-Linking-MS (XL-MS)), EGFR (Proximity Label-MS), ERBB2 (Proximity Label-MS), FGFR1 (Affinity Capture-MS), FGFR4 (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
NfKb-p65/p50	“down-regulates quantity by repression”	EPCAM	“transcriptional regulation”
CBP/p300	“up-regulates quantity by expression”	EPCAM	“transcriptional regulation”
ZEB1	“down-regulates quantity by repression”	EPCAM	“transcriptional regulation”

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
CTNNB1-EPCAM-FHL2-LEF1 complex	4	CTNNB1, EPCAM, FHL2, LEF1

Disease & clinical

Genetic variants

Variant evidence for EPCAM: 1,142 ClinVar records (139 pathogenic / likely pathogenic); 1 CIViC cancer variant; 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,142 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	120
Likely pathogenic	19
Uncertain significance	588
Likely benign	316
Benign	42

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 139 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
12774	NM_002354.3(EPCAM):c.499dup (p.Gln167fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
12771	NM_002354.3(EPCAM):c.491+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	7
157604	NM_002354.3(EPCAM):c.492-2A>G	Pathogenic	criteria provided, multiple submitters, no conflicts	4
800510	NM_002354.3(EPCAM):c.265C>T (p.Gln89Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3255333	NM_002354.3(EPCAM):c.227C>G (p.Ser76Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1801655	NM_002354.3(EPCAM):c.1A>G (p.Met1Val)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
40256	NM_002354.3(EPCAM):c.412C>T (p.Arg138Ter)	Pathogenic	criteria provided, single submitter	3
188070	NM_002354.2(EPCAM):c.859-?_*415del	Pathogenic	criteria provided, single submitter	1
220128	NM_002354.3(EPCAM):c.491+1G>T	Pathogenic	criteria provided, single submitter	1
239120	NM_002354.3(EPCAM):c.133C>T (p.Gln45Ter)	Pathogenic	criteria provided, single submitter	1
239127	NM_002354.3(EPCAM):c.429G>A (p.Trp143Ter)	Pathogenic	criteria provided, single submitter	1
239132	NM_002354.3(EPCAM):c.523C>T (p.Gln175Ter)	Pathogenic	criteria provided, single submitter	1
433577	NM_002354.2(EPCAM):c.904-?_945+?del	Pathogenic	criteria provided, single submitter	1
579230	NM_002354.3(EPCAM):c.712del (p.Glu238fs)	Pathogenic	criteria provided, single submitter	1
584581	NM_000251.2(MSH2):c.(?-1)_(1276+1_1277-1)del	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore EPCAM’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 740):

Position(s)	Effect	Δscore	Sites
2:47369579	donor_gain	1.0000
2:47373461–47373462	acceptor_loss	1.0000	5
2:47373571–47373572	donor_loss	1.0000	5
2:47373575	donor_loss	1.0000
2:47378951–47378952	acceptor_loss	1.0000	5
2:47379767–47379768	acceptor_loss	1.0000	6
2:47379970–47379971	donor_loss	1.0000	5
2:47369582–47369583	donor_loss	0.9900	5
2:47373454–47373455	acceptor_gain	0.9900	2
2:47373572	donor_loss	0.9900

AlphaMissense

733 missense substitutions predicted likely pathogenic (of 2,073 scored), across 196 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D253	8	0.985	0.994
F105	8	0.971	0.997
D219	8	0.958	0.988
D208	8	0.929	0.972
N120	8	0.926	0.998
D92	8	0.906	0.954
H150	8	0.826	0.923
C99	7	0.994	0.998
C118	7	0.994	0.998
C135	7	0.992	0.997
C66	7	0.991	0.997
C59	7	0.984	0.993
C110	7	0.983	0.991
W117	7	0.981	0.997
C116	7	0.978	0.989
C38	7	0.972	0.991
C29	7	0.968	0.984
C48	7	0.966	0.991
C46	7	0.957	0.983
Q109	7	0.948	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000391

Disease associations

OMIM: gene MIM:185535 | disease phenotypes: MIM:613659, MIM:613217, MIM:613244, MIM:114480, MIM:120435

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital diarrhea 5 with tufting enteropathy	Definitive	Autosomal recessive	5
Lynch syndrome 8	Definitive	Autosomal dominant	4
Lynch syndrome	Definitive	Autosomal dominant	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
Lynch syndrome	Definitive	AD
hereditary breast carcinoma	Refuted	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 10 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Adult solid tumours for rare disease	green
DDG2P	green
GI tract tumours	green
Gastrointestinal epithelial barrier disorders	green
Infantile enterocolitis & monogenic inflammatory bowel disease	green
Inherited MMR deficiency (Lynch syndrome)	green
Inherited polyposis and early onset colorectal cancer - germline testing	green
Intestinal failure or congenital diarrhoea	green
Paediatric disorders	green

Mondo (9): colon carcinoma (MONDO:0002032), gastric cancer (MONDO:0001056), congenital diarrhea 5 with tufting enteropathy (MONDO:0013184), hereditary neoplastic syndrome (MONDO:0015356), Lynch syndrome 8 (MONDO:0013196), hereditary breast carcinoma (MONDO:0016419), Lynch syndrome 1 (MONDO:0007356), hereditary nonpolyposis colon cancer (MONDO:0018630), Lynch syndrome (MONDO:0005835)

Orphanet (5): Inherited cancer-predisposing syndrome (Orphanet:140162), Congenital tufting enteropathy (Orphanet:92050), Lynch syndrome (Orphanet:144), Hereditary breast cancer (Orphanet:227535), Hereditary nonpolyposis colon cancer (Orphanet:443909)

HPO phenotypes

showing 60 of 97 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000202	Orofacial cleft
HP:0000453	Choanal atresia
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000588	Optic disc coloboma
HP:0000613	Photophobia
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000951	Abnormality of the skin
HP:0001123	Visual field defect
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001369	Arthritis
HP:0001371	Flexion contracture
HP:0001402	Hepatocellular carcinoma
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001824	Weight loss
HP:0001944	Dehydration
HP:0002013	Vomiting
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002023	Anal atresia
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002028	Chronic diarrhea
HP:0002041	Intractable diarrhea
HP:0002076	Migraine
HP:0002167	Abnormal speech pattern
HP:0002239	Gastrointestinal hemorrhage
HP:0002354	Memory impairment
HP:0002376	Developmental regression
HP:0002516	Increased intracranial pressure
HP:0002570	Steatorrhea
HP:0002611	Cholestatic liver disease
HP:0002652	Skeletal dysplasia
HP:0002671	Basal cell carcinoma
HP:0002893	Pituitary adenoma
HP:0002894	Neoplasm of the pancreas
HP:0002896	Neoplasm of the liver
HP:0003002	Breast carcinoma
HP:0003003	Colon cancer
HP:0003006	Neuroblastoma
HP:0003270	Abdominal distention
HP:0003401	Paresthesia
HP:0003584	Late onset
HP:0003593	Infantile onset
HP:0003596	Middle age onset
HP:0003623	Neonatal onset
HP:0004374	Hemiplegia/hemiparesis
HP:0004377	Hematological neoplasm

GWAS associations

2 associations:

Study	Trait	p-value
GCST009568_1	epithelial cell adhesion molecule levels	7e-16
GCST90026413_4	Severe insulin-deficient type 2 diabetes	2e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0010574	epithelial cell adhesion molecule measurement

MeSH disease descriptors

5 disease descriptors:

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C562840	Breast Cancer, Familial *(supp.)*
C567685	Colorectal Cancer, Hereditary Nonpolyposis, Type 8 *(supp.)*
C567703	Diarrhea 5, With Tufting Enteropathy, Congenital *(supp.)*
C537261	Lynch syndrome I (site-specific colonic cancer) *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580493 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the EPCAM protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

10 curated-mechanism drugs:

Drug	Modality	Max phase
CATUMAXOMAB	Antibody	4
EDRECOLOMAB	Antibody	3
IGN-101	Unknown	3
OPORTUZUMAB MONATOX	Antibody drug conjugate	3
ADECATUMUMAB	Antibody	2
CITATUZUMAB BOGATOX	Antibody drug conjugate	2
ING-1	Unknown	2
SOLITOMAB	Antibody	2
TUCOTUZUMAB CELMOLEUKIN	Antibody drug conjugate	2
MOC31-PE	Unknown	1

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

3’ Exon Deletion (disruptive inframe deletion).

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.33	Kd	0.472	nM	CHEMBL5653589
9.33	ED50	0.472	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148324: Binding affinity to human EPCAM incubated for 45 mins by Kinobead based pull down assay	kd	0.0005	uM

CTD chemical–gene interactions

81 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
sodium arsenite	affects reaction, increases expression, increases reaction, decreases reaction, decreases expression	4
bisphenol A	decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	3
Tretinoin	affects expression, decreases expression, increases expression	3
Paclitaxel	affects cotreatment, increases expression, decreases expression	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Decitabine	affects expression, affects methylation	2
Panobinostat	increases expression, affects cotreatment	2
Cisplatin	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
napabucasin	decreases expression	1
XMU-MP-1	decreases expression, decreases reaction	1
dicrotophos	decreases expression	1
lead acetate	decreases expression	1
methylparaben	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	increases expression	1
ferrous chloride	increases expression	1
cupric chloride	decreases expression	1
nickel sulfate	decreases expression	1
artemisinin	decreases expression	1
3-hydroxyflavone	decreases expression	1
casticin	decreases expression, increases reaction, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651366	Binding	Binding affinity to human EPCAM incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

8 cell lines: 4 cancer cell line, 2 spontaneously immortalized cell line, 1 finite cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1C4	Abcam A-431 EPCAM KO	Cancer cell line	Female
CVCL_B3ZD	WG4190	Finite cell line	Male
CVCL_D2TL	CHO/EpCAM	Spontaneously immortalized cell line	Female
CVCL_D8KV	Ubigene HCT 116 EPCAM KO	Cancer cell line	Male
CVCL_E0ZT	Ubigene NCI-H292 EPCAM KO	Cancer cell line	Female
CVCL_E6Q8	Genomeditech CHO-K1 H_EPCAM	Spontaneously immortalized cell line	Female
CVCL_E8GZ	CT26-hEpCam-LZ	Cancer cell line	Female
CVCL_UE39	293T human Epcam	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 401 trials:

NCT	Phase	Status	Title
NCT00190697	Phase 4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	Phase 4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	Phase 4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	Phase 4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	Phase 4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	Phase 4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	Phase 4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	Phase 4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	Phase 4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	Phase 4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	Phase 4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	Phase 4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	Phase 4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	Phase 4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	Phase 4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	Phase 4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	Phase 4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	Phase 4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	Phase 4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	Phase 4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	Phase 4	UNKNOWN	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	Phase 4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	Phase 4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	Phase 4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	Phase 4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00566644	Phase 3	TERMINATED	Intrauterine Levonorgestrel and Observation or Observation Alone in Preventing Atypical Endometrial Hyperplasia and Endometrial Cancer in Women With Hereditary Non-Polyposis Colorectal Cancer or Lynch Syndrome
NCT02000089	Phase 3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT02813824	Phase 3	ACTIVE_NOT_RECRUITING	Effect of Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome
NCT02912559	Phase 3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair
NCT04711434	Phase 3	UNKNOWN	PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients
NCT07609901	Phase 3	NOT_YET_RECRUITING	Preventive Dendritic Cell Vaccination for Lynch Syndrome Carriers
NCT00001806	Phase 3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	Phase 3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	Phase 3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	Phase 3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	Phase 3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	Phase 3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	Phase 3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	Phase 3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	Phase 3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	Phase 3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	Phase 3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	Phase 3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	Phase 3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer
NCT00003695	Phase 3	COMPLETED	Chemotherapy With or Without Surgery in Treating Patients With Stage II or Stage III Ovarian Cancer
NCT00003998	Phase 3	COMPLETED	Carboplatin Plus Paclitaxel or Docetaxel in Treating Patients With Ovarian Epithelial Cancer
NCT00004115	Phase 3	UNKNOWN	Monoclonal Antibody Therapy in Treating Patients With Ovarian Cancer or Primary Peritoneal Cancer in Remission Following Surgery and Chemotherapy
NCT00004166	Phase 3	COMPLETED	Amifostine in Treating Patients With Ovarian Epithelial Cancer Who Are Receiving Chemotherapy
NCT00004921	Phase 3	COMPLETED	High-Dose Chemotherapy Compared With Standard Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer That Has Been Removed During Surgery
NCT00004934	Phase 3	COMPLETED	Paclitaxel and Carboplatin With or Without Epirubicin in Treating Patients With Stage IIB, Stage III, or Stage IV Invasive Ovarian Epithelial, Fallopian Tube, or Peritoneal Cancer
NCT00005590	Phase 3	COMPLETED	Levofloxacin to Prevent Infection Following Chemotherapy in Treating Patients With Solid Tumors or Lymphoma
NCT00006356	Phase 3	TERMINATED	Chemotherapy With or Without Surgery in Treating Patients With Recurrent Ovarian Cancer
NCT00006453	Phase 3	COMPLETED	Carboplatin With or Without Gemcitabine in Treating Patients With Advanced Ovarian Epithelial Cancer That Has Not Responded to Previous Chemotherapy
NCT00006454	Phase 3	COMPLETED	Paclitaxel Plus Carboplatin With or Without Topotecan in Treating Patients With Stage IIB, Stage III, or Stage IV Ovarian Epithelial Cancer
NCT00011986	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer
NCT00028743	Phase 3	COMPLETED	Combination Chemotherapy Regimens in Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
NCT00033605	Phase 3	COMPLETED	Octreotide in Preventing Diarrhea in Patients Who Are Undergoing Radiation Therapy to the Pelvis
NCT00043082	Phase 3	COMPLETED	S0200 Carboplatin With or Without Doxil in Patients With Recurrent Ovarian Cancer

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for EPCAM across ~30M SureChEMBL compounds — explore on Sugi Predict.