EPGN

Summary

EPGN (epithelial mitogen, HGNC:17470) is a protein-coding gene on chromosome 4q13.3, encoding Epigen (Q6UW88). Promotes the growth of epithelial cells.

The protein encoded by this gene is a member of the epidermal growth factor family. Members of this family are ligands for the epidermal growth factor receptor and play a role in cell survival, proliferation and migration. This protein has been reported to have high mitogenic activity but low affinity for its receptor. Expression of this transcript and protein have been reported in cancer specimens of the breast, bladder, and prostate. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 255324 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001270989

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17470
Approved symbol	EPGN
Name	epithelial mitogen
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	EPG, PRO9904, ALGV3072
Ensembl gene	ENSG00000182585
Ensembl biotype	protein_coding
OMIM	618717
Entrez	255324

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000332112, ENST00000413830, ENST00000446430, ENST00000502358, ENST00000502835, ENST00000503098, ENST00000505212, ENST00000509145, ENST00000514968

RefSeq mRNA: 6 — MANE Select: NM_001270989 NM_001013442, NM_001270989, NM_001270990, NM_001270991, NM_001270992, NM_001270993

CCDS: CCDS34010, CCDS59475, CCDS59476, CCDS59477, CCDS59478, CCDS59479

Canonical transcript exons

ENST00000413830 — 5 exons

Exon	Start	End
ENSE00001305227	74312185	74312305
ENSE00001611735	74308470	74308576
ENSE00001638593	74309093	74309182
ENSE00001707490	74314580	74316789
ENSE00001727139	74313018	74313170

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 89.46.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5270 / max 206.4206, expressed in 256 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48267	1.0227	235
48268	0.5043	148

Top tissues by expression

126 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
esophagus mucosa	UBERON:0002469	89.46	gold quality
lower esophagus mucosa	UBERON:0035834	81.46	gold quality
vagina	UBERON:0000996	69.92	gold quality
esophagus	UBERON:0001043	67.49	gold quality
skin of leg	UBERON:0001511	66.35	gold quality
zone of skin	UBERON:0000014	63.91	gold quality
vermiform appendix	UBERON:0001154	62.30	gold quality
skin of abdomen	UBERON:0001416	61.29	gold quality
right lung	UBERON:0002167	60.12	gold quality
tonsil	UBERON:0002372	59.89	gold quality
bone marrow cell	CL:0002092	59.35	silver quality
ectocervix	UBERON:0012249	56.34	gold quality
mucosa of transverse colon	UBERON:0004991	56.15	gold quality
upper lobe of left lung	UBERON:0008952	54.79	gold quality
left uterine tube	UBERON:0001303	53.24	gold quality
bone marrow	UBERON:0002371	52.59	silver quality
omental fat pad	UBERON:0010414	52.24	gold quality
lung	UBERON:0002048	51.98	gold quality
uterine cervix	UBERON:0000002	51.54	gold quality
placenta	UBERON:0001987	49.20	gold quality
minor salivary gland	UBERON:0001830	49.10	gold quality
colonic epithelium	UBERON:0000397	49.01	silver quality
saliva-secreting gland	UBERON:0001044	47.63	gold quality
right atrium auricular region	UBERON:0006631	47.49	gold quality
testis	UBERON:0000473	46.99	gold quality
left testis	UBERON:0004533	46.98	gold quality
right testis	UBERON:0004534	46.77	gold quality
fallopian tube	UBERON:0003889	46.69	gold quality
calcaneal tendon	UBERON:0003701	46.56	gold quality
lymph node	UBERON:0000029	46.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.42
E-MTAB-6058	no	50.56
E-MTAB-6379	no	2.25

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• cloning of a related gene in mouse (PMID:112783)
• EPG is an EGF-like growth factor and a low affinity ligand (PMID:15611079)
• Study shows how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. Results reveal how responses to different EGFR ligands are defined by receptor dimerization strength and signaling dynamics. These findings have broad implications for understanding receptor tyrosine kinase (RTK) signaling specificity. (PMID:28988771)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epgn	ENSMUSG00000035020
rattus_norvegicus	Epgn	ENSRNOG00000002782

Paralogs (5): AREG (ENSG00000109321), HBEGF (ENSG00000113070), EREG (ENSG00000124882), TGFA (ENSG00000163235), BTC (ENSG00000174808)

Protein

Protein identifiers

Epigen — Q6UW88 (reviewed: Q6UW88)

Alternative names: Epithelial mitogen

All UniProt accessions (3): A0PK19, Q6UW88, H3BM13

UniProt curated annotations — full annotation on UniProt →

Function. Promotes the growth of epithelial cells. May stimulate the phosphorylation of EGFR and mitogen-activated protein kinases.

Subcellular location. Membrane Membrane Secreted Secreted Secreted Secreted.

Isoforms (7)

UniProt ID	Names	Canonical?
Q6UW88-1	1	yes
Q6UW88-2	2
Q6UW88-3	3, B
Q6UW88-4	4, E
Q6UW88-5	5, F
Q6UW88-6	6, G
Q6UW88-7	7, D

RefSeq proteins (6): NP_001013460, NP_001257918, NP_001257919, NP_001257920, NP_001257921, NP_001257922 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain

UniProt features (23 total): splice variant 5, disulfide bond 3, strand 3, sequence conflict 2, topological domain 2, turn 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5WB8	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UW88-F1	67.25	0.08

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 (3): 86–95, 60–73, 68–84

Glycosylation sites (2): 37, 41

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-177929	Signaling by EGFR
R-HSA-179812	GRB2 events in EGFR signaling
R-HSA-180292	GAB1 signalosome
R-HSA-180336	SHC1 events in EGFR signaling
R-HSA-182971	EGFR downregulation
R-HSA-212718	EGFR interacts with phospholipase C-gamma
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5638303	Inhibition of Signaling by Overexpressed EGFR
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling

MSigDB gene sets: 122 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, REACTOME_GAB1_SIGNALOSOME, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOMF_GROWTH_FACTOR_ACTIVITY, REACTOME_MEMBRANE_TRAFFICKING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, chr4q13, GOBP_ORGANELLE_FISSION, GOBP_ERBB_SIGNALING_PATHWAY, GOCC_COATED_VESICLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (8): MAPK cascade (GO:0000165), angiogenesis (GO:0001525), epidermal growth factor receptor signaling pathway (GO:0007173), positive regulation of cell population proliferation (GO:0008284), positive regulation of MAPK cascade (GO:0043410), positive regulation of mitotic nuclear division (GO:0045840), positive regulation of epithelial cell proliferation (GO:0050679), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (5): epidermal growth factor receptor binding (GO:0005154), growth factor activity (GO:0008083), transmembrane receptor protein tyrosine kinase activator activity (GO:0030297), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), clathrin-coated endocytic vesicle membrane (GO:0030669), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Signaling by EGFR	5
Intracellular signaling by second messengers	1
Signaling by Receptor Tyrosine Kinases	1
PI3K/AKT Signaling in Cancer	1
Signaling by Overexpressed Wild-Type EGFR in Cancer	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
ESR-mediated signaling	1
Extra-nuclear estrogen signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
signaling receptor activator activity	2
cellular anatomical structure	2
intracellular signaling cassette	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
ERBB signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of mitotic nuclear division	1
positive regulation of nuclear division	1
positive regulation of cell cycle process	1
mitotic nuclear division	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
growth factor receptor binding	1
receptor ligand activity	1
transmembrane receptor protein tyrosine kinase activity	1
protein tyrosine kinase activator activity	1
binding	1
signaling receptor binding	1
membrane	1
cell periphery	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1

Protein interactions and networks

STRING

493 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPGN	EGFR	P00533	992
EPGN	BTC	P35070	924
EPGN	AREG	P15514	884
EPGN	HBEGF	Q99075	857
EPGN	EGF	P01133	819
EPGN	ERBB4	Q15303	746
EPGN	EREG	O14944	678
EPGN	ERBB3	P21860	623
EPGN	NRG2	O14511	615
EPGN	NRG4	Q8WWG1	613
EPGN	TGFA	P01135	567
EPGN	NRG3	P56975	526
EPGN	ERBB2	P04626	506
EPGN	TMEFF2	Q9UIK5	501
EPGN	NRG1	P98202	460

IntAct

6 interactions, top by confidence:

A	B	Type	Score
EGF	EGFR	psi-mi:“MI:0915”(physical association)	0.970
EGFR	EPGN	psi-mi:“MI:0407”(direct interaction)	0.620
EPGN	EGFR	psi-mi:“MI:0407”(direct interaction)	0.620
APP	EPGN	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (4): EPGN (Two-hybrid), EPGN (Two-hybrid), EPGN (Two-hybrid), EPGN (Two-hybrid)

ESM2 similar proteins: A0A023FF81, A0A141SFN5, A0A146B485, A0A1B0GWG4, A0A6G9KJM3, A0A7H0DMZ6, A0A8U0LTM5, A0A8U0LTN3, A0A8U0LTT7, A0A8U0LTT9, A0A8U0LU66, A6QQ93, B1B5J0, D5KXH3, O45201, O57166, P01136, P08072, P08441, P09258, P0DOP9, P0DOQ0, P0DQX9, P0DSL4, P11321, P15137, P20494, P21014, P22815, P24358, P34259, P35767, P35768, P45442, Q07FZ2, Q10128, Q1L867, Q5EG71, Q5R9E4, Q6DE06

Diamond homologs: A0A8U0LTM5, A0A8U0LTT7, P01133, P01134, P01135, P07522, P0DQX9, P0DSL4, P35070, P48030, P55244, P98135, P98138, Q00968, Q01580, Q05928, Q06186, Q06922, Q09118, Q17QD6, Q5EG71, Q6UW88, Q924X1, Q95ND4, Q99075, Q9BEA0, Q9J524, Q9QYM9, Q9TTC5, Q9UIK5, Q9W7C5, A0A7H0DMZ6, O14944, O57166, P01136, P0DOP9, P0DOQ0, P20494, P56974, Q61521

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
EPGN	up-regulates	ERBB4	binding
EPGN	up-regulates	EGFR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

843 predictions. Top by Δscore:

Variant	Effect	Δscore
4:74312180:CCTA:C	acceptor_loss	1.0000
4:74312183:A:AG	acceptor_gain	1.0000
4:74312183:A:G	acceptor_loss	1.0000
4:74312183:AGCT:A	acceptor_gain	1.0000
4:74312184:G:GA	acceptor_gain	1.0000
4:74312184:GC:G	acceptor_gain	1.0000
4:74312184:GCT:G	acceptor_gain	1.0000
4:74312184:GCTG:G	acceptor_gain	1.0000
4:74312184:GCTGA:G	acceptor_gain	1.0000
4:74312301:TGCAG:T	donor_loss	1.0000
4:74312303:CAG:C	donor_loss	1.0000
4:74312304:AGG:A	donor_loss	1.0000
4:74312305:GGTAA:G	donor_loss	1.0000
4:74312306:G:A	donor_loss	1.0000
4:74313127:T:G	donor_gain	1.0000
4:74313127:T:TG	donor_gain	1.0000
4:74308576:GGTA:G	donor_loss	0.9900
4:74308577:G:GG	donor_gain	0.9900
4:74308578:T:A	donor_loss	0.9900
4:74309086:A:AG	acceptor_gain	0.9900
4:74309091:A:AG	acceptor_gain	0.9900
4:74309092:G:GG	acceptor_gain	0.9900
4:74309092:GCA:G	acceptor_gain	0.9900
4:74312186:T:A	acceptor_gain	0.9900
4:74312302:GCAG:G	donor_gain	0.9900
4:74312306:G:GG	donor_gain	0.9900
4:74309092:GC:G	acceptor_gain	0.9800
4:74309092:GCAAT:G	acceptor_gain	0.9800
4:74312179:TCCTA:T	acceptor_gain	0.9800
4:74312180:CCTAG:C	acceptor_gain	0.9800

AlphaMissense

987 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:74313046:T:A	C95S	0.994
4:74313047:G:C	C95S	0.994
4:74312253:T:A	C68S	0.992
4:74312254:G:C	C68S	0.992
4:74313038:G:T	G92V	0.990
4:74312262:G:T	G71C	0.987
4:74313045:G:C	R94S	0.986
4:74313045:G:T	R94S	0.986
4:74312301:T:A	C84S	0.985
4:74312302:G:C	C84S	0.985
4:74313046:T:C	C95R	0.985
4:74313047:G:A	C95Y	0.985
4:74313047:G:T	C95F	0.985
4:74312263:G:A	G71D	0.984
4:74312268:T:A	C73S	0.983
4:74312269:G:C	C73S	0.983
4:74313019:T:A	C86S	0.983
4:74313020:G:C	C86S	0.983
4:74313048:T:G	C95W	0.982
4:74312255:C:G	C68W	0.981
4:74313130:A:C	S123R	0.979
4:74313132:T:A	S123R	0.979
4:74313132:T:G	S123R	0.979
4:74312254:G:A	C68Y	0.978
4:74312263:G:T	G71V	0.978
4:74312302:G:A	C84Y	0.978
4:74313019:T:C	C86R	0.977
4:74312303:C:G	C84W	0.976
4:74313021:T:G	C86W	0.976
4:74313038:G:A	G92E	0.976

dbSNP variants (sampled 300 via entrez): RS1000002835 (4:74311775 T>C), RS1000036672 (4:74315211 C>A,T), RS1000195043 (4:74315602 A>G), RS1000602298 (4:74310384 C>G), RS1001142070 (4:74310647 T>A), RS1001589668 (4:74314945 A>C,G), RS1001870838 (4:74311704 A>G), RS1002214153 (4:74308300 T>C), RS1002647768 (4:74310269 C>A,T), RS1002808757 (4:74306488 G>A), RS1002883872 (4:74313664 C>T), RS1003486229 (4:74306688 G>A,T), RS1004425975 (4:74312667 G>A), RS1004469092 (4:74307398 A>T), RS1004605824 (4:74310704 A>G)

Disease associations

OMIM: gene MIM:618717 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001533_9	Immune reponse to smallpox (secreted IL-1beta)	7.000000e-09
GCST001585_33	Breast size	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, affects expression	4
sodium arsenite	increases expression	3
Smoke	decreases expression, increases abundance, increases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
lead acetate	increases expression	1
hydroxyhydroquinone	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
sulforaphane	increases expression	1
potassium chromate(VI)	decreases expression	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
diallyl trisulfide	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Cadmium	decreases expression	1
Coal	decreases expression, increases abundance	1
Copper	decreases expression, affects cotreatment	1
Gold	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	increases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.