EGF

Summary

EGF (epidermal growth factor, HGNC:3229) is a protein-coding gene on chromosome 4q25, encoding Pro-epidermal growth factor (P01133). EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. In precision oncology, EGF EXPRESSION is associated with resistance to Cetuximab in Head And Neck Squamous Cell Carcinoma (CIViC Level D).

This gene encodes a member of the epidermal growth factor superfamily. The encoded preproprotein is proteolytically processed to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by binding with high affinity to the cell surface receptor, epidermal growth factor receptor. Defects in this gene are the cause of hypomagnesemia type 4. Dysregulation of this gene has been associated with the growth and progression of certain cancers. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed.

Source: NCBI Gene 1950 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial primary hypomagnesemia with normocalciuria and normocalcemia (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 27
• Clinical variants (ClinVar): 657 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_001963

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3229
Approved symbol	EGF
Name	epidermal growth factor
Location	4q25
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138798
Ensembl biotype	protein_coding
OMIM	131530
Entrez	1950

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 protein_coding, 7 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000265171, ENST00000502579, ENST00000502723, ENST00000503392, ENST00000504633, ENST00000509793, ENST00000509996, ENST00000511228, ENST00000537316, ENST00000540840, ENST00000541061, ENST00000544918, ENST00000652245, ENST00000868529, ENST00000868530, ENST00000868531, ENST00000868532, ENST00000868533, ENST00000934497, ENST00000951655

RefSeq mRNA: 4 — MANE Select: NM_001963 NM_001178130, NM_001178131, NM_001357021, NM_001963

CCDS: CCDS3689, CCDS54794, CCDS54795, CCDS93566

Canonical transcript exons

ENST00000265171 — 24 exons

Exon	Start	End
ENSE00000736651	109940946	109941145
ENSE00000736653	109943842	109944069
ENSE00000736654	109945073	109945275
ENSE00000736655	109959312	109959437
ENSE00000736658	109963173	109963298
ENSE00000736659	109964401	109964537
ENSE00000736660	109968971	109969119
ENSE00000736665	109976012	109976235
ENSE00000736668	109979972	109980139
ENSE00000736670	109980826	109980975
ENSE00000736674	109987744	109987860
ENSE00000736676	109988584	109988709
ENSE00001081339	110011202	110013766
ENSE00001081340	109912883	109913462
ENSE00003514951	110004505	110004622
ENSE00003523921	109993247	109993369
ENSE00003537054	109983422	109983541
ENSE00003565191	109974703	109974807
ENSE00003600038	109961863	109961985
ENSE00003601705	109943254	109943435
ENSE00003617998	109960867	109960989
ENSE00003648899	109994733	109994880
ENSE00003660401	109999679	109999846
ENSE00003686711	110008152	110008230

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 99.43.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6442 / max 45.1507, expressed in 289 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49251	0.4269	203
49252	0.1447	44
49253	0.0726	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.43	gold quality
body of pancreas	UBERON:0001150	94.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.89	gold quality
adult mammalian kidney	UBERON:0000082	92.61	gold quality
nephron tubule	UBERON:0001231	92.48	gold quality
gastrocnemius	UBERON:0001388	91.99	gold quality
biceps brachii	UBERON:0001507	91.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.51	gold quality
muscle of leg	UBERON:0001383	90.42	gold quality
muscle organ	UBERON:0001630	89.97	gold quality
skeletal muscle organ	UBERON:0014892	89.97	gold quality
skeletal muscle tissue	UBERON:0001134	89.63	gold quality
kidney epithelium	UBERON:0004819	89.14	gold quality
kidney	UBERON:0002113	89.05	gold quality
deltoid	UBERON:0001476	88.89	gold quality
vastus lateralis	UBERON:0001379	88.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.51	gold quality
secondary oocyte	CL:0000655	88.03	gold quality
quadriceps femoris	UBERON:0001377	87.69	gold quality
oocyte	CL:0000023	86.53	gold quality
gluteal muscle	UBERON:0002000	86.47	gold quality
pancreas	UBERON:0001264	84.87	gold quality
metanephric glomerulus	UBERON:0004736	84.83	gold quality
muscle tissue	UBERON:0002385	84.34	gold quality
cortex of kidney	UBERON:0001225	84.20	gold quality
adult organism	UBERON:0007023	84.10	gold quality
renal glomerulus	UBERON:0000074	83.69	gold quality
tibialis anterior	UBERON:0001385	83.69	gold quality
metanephros cortex	UBERON:0010533	82.43	gold quality
monocyte	CL:0000576	82.32	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	8827.30
E-CURD-119	yes	6702.88
E-ANND-3	yes	17.66
E-CURD-135	no	1692.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
HBA1	Activation
HBB	Activation
MED1	Activation
STAT1	Unknown

Upstream regulators (CollecTRI, top): AP1, AR, CEBPB, CEBPD, CEBPE, CTCF, E2F1, EGR1, ELK3, EPAS1, ESR1, ETS2, FOS, FOSL1, FOXC1, GCFC2, GLI3, HIF1A, HNF1B, HNF4A, HTATIP2, IRF6, JUN, JUNB, JUND, KLF5, MYB, MYC, NCOA2, NFATC4, NFKB1, NFKB, NR0B1, NR2E1, NR4A1, NRG1, PAX6, POU1F1, RELA, SMAD1

miRNA regulators (miRDB)

61 targeting EGF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429

Literature-anchored findings (GeneRIF, showing 40)

• The data presented here demonstrate that, in contrast to activation by the cytokine, growth hormone (GH), the activation of STAT5b by the growth factor, epidermal growth factor (EGF), requires overexpression of the EGF receptor (EGFR). (PMID:11751923)
• ERK negatively regulates the epidermal growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase (PMID:11896055)
• assess the levels of EGF during pregnancy and to determine whether or not low concentrations are associated with fetal untrauterine growth retardation (PMID:11903419)
• Epidermal growth factor contains both positive and negative determinants for interaction with ErbB-2/ErbB-3 heterodimers (PMID:11914075)
• connecting segment between EGF-like domains in factor IX contributes to stimulation by factor VIIIa and its A2 domain (PMID:11925427)
• Detecting protein-phospholipid interactions. Epidermal growth factor-induced activation of phospholipase D1b in situ (PMID:11950840)
• Epidermal growth factor-mediated activation of the ETS domain transcription factor Elk-1 requires nuclear calcium (PMID:11971908)
• blocking of EGF-induced activation of Akt by inhibiting Src family kinases (PMID:11994282)
• expression and role of EGF in fat cells and insulin resistance in humans (PMID:12138086)
• effect of epidermal growth factor on vascular endothelial growth factor secretion by endometrial stromal cells (PMID:12141529)
• Differential effects of FGF4, EGF and TGFB1 on functional development of stromal layers (progenitor cell-outputs) in acute myeloid leukemia (PMID:12163055)
• These results suggest that epidermal growth factor treatment increased p11 bound to cPLA(2) may lead to the late suppression of AA release induced by EGF. (PMID:12163506)
• EGF protein levels were decreased in the prefrontal cortex and striatum of schizophrenic patients (PMID:12192610)
• In repair model, both EGF and TGFalpha stimulated the wound closure strongly by increased cell migration. (PMID:12202942)
• EGF stimulates Ca(2+) influx via a mechanism distinct from capacitative Ca(2+) influx induced by carbachol and thapsigargin (PMID:12368284)
• Human cytomegalovirus infection inhibits epidermal growth factor (EGF) signalling by targeting EGF receptors (PMID:12388817)
• binds to a receptor on Trypanosoma cruzi amastigotes inducing signal transduction events and cell proliferation (PMID:12425525)
• Levels of this factor are lowered in cryptorchism. (PMID:12508124)
• Fatty acid synthase and sterol regulatory element binding protein-1c mRNAs are coordinately modulated by changes in EGF signalling in breast cancer cells. (PMID:12531699)
• EGF enhances beta-adrenergic responsiveness by upregulating beta(2)-adrenergic receptor at transcriptional level. Stimulatory effect of EGF on beta(2)-adrenergic receptor signaling mediated by MAPK pathway and independent of PKC activation. (PMID:12540376)
• epidermal growth factor-induced connexin 43 gap junction communication is regulated by big mitogen-activated protein kinase1/ERK5 (PMID:12637502)
• Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling. (PMID:12643788)
• The expression of EGF in hepatocellular carcinoma, HCC underlies the overexpression of VEGF in HCC. (PMID:12667326)
• EGF trafficking is facilitated by cortactin linking receptor endocytosis to actin polymerization (PMID:12672817)
• A431 squamous cell carcinoma cells have an increased expression of EGF receptor. There is no difference in expression of EGF receptor or in the EGF-induced phospohorylation in A431 cells and clonal variants. (PMID:12722480)
• EGF protects against oxidative stress disruption of intestinal barrier by stabilizing F-Actin, largely through the activation of PLC-gamma and downregulation of iNOS pathway. (PMID:12788694)
• EGF can protect tumor cells from TNF-alpha-induced apoptosis through activation of PKC-delta (PMID:12795334)
• EGF decreases the antiproliferative effect of TGFbeta in primary human ovarian cancer cells (PMID:12879019)
• epidermal growth factor induces keratin 16 expression through cooperation of transcription factors Sp1 and c-Jun (PMID:12954631)
• epidermal growth factor internalization does not require either clathrin or AP-2 (PMID:12960147)
• Biological dressing effect of cultured epidermal sheets(CESs) is mediated by EGF family, TGF-beta, and VEGF. Ability of EGF to enhance growth factor production in CESs. (PMID:14507446)
• EGF and angiotensin II activation of phospholipase Cgamma through src is mediated by GIT1 (PMID:14523024)
• There was decreased EGF mRNA expression in the stenotic tissue after clinical ureteropelvic junction obstruction. Alteration of EGF expression may be involved in the pathogenesis of congenital hydronephrosis. (PMID:14614718)
• Soluble protein components of the cytosol from A431 cells are shown to dramatically enhance binding of the EGFR to F-actin in a saturable, concentration-dependent fashion. (PMID:14651960)
• EGF signaling through MAPK increases TIF2/GRIP1 coactivation of androgen receptor transactivation in recurrent prostate cancer (PMID:14662770)
• Etk activation is essential for transducing the EGF-induced apoptotic signaling in breast cancer cells. (PMID:14676838)
• Fibroblast proliferation, differentiation into myofibroblasts, & increased collagen synthesis are regulated via a CTGF-dependent pathway in concert with either EGF or IGF-2. (PMID:15003992)
• EGF-mediated induction of fibronectin expression occurs at the post-transcriptional level and involves PKCdelta signaling pathway. (PMID:15175028)
• epidermal growth factor-induced chemotaxis requires sphingosine-1-phosphate phosphatase 1 (PMID:15180992)
• Supplementation of enteral feeds with EGF reduces incidence of intestinal inflammation and necrotizing enterocolitis. Review. (PMID:15183666)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	egf	ENSDARG00000052739
mus_musculus	Egf	ENSMUSG00000028017
rattus_norvegicus	Egf	ENSRNOG00000053979
drosophila_melanogaster	Lrp4	FBGN0030706
caenorhabditis_elegans		WBGENE00004374

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), NID1 (ENSG00000116962), LRP1 (ENSG00000123384), LDLR (ENSG00000130164), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), LRP12 (ENSG00000147650), VLDLR (ENSG00000147852), LRP8 (ENSG00000157193), LRP5 (ENSG00000162337), LRP1B (ENSG00000168702), LRP10 (ENSG00000197324)

Protein

Protein identifiers

Pro-epidermal growth factor — P01133 (reviewed: P01133)

All UniProt accessions (2): P01133, A0A494C018

UniProt curated annotations — full annotation on UniProt →

Function. EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. Can induce neurite outgrowth in motoneurons of the pond snail Lymnaea stagnalis in vitro.

Subunit / interactions. Interacts with EGFR and promotes EGFR dimerization. Interacts with RHBDF2. Interacts with RHBDF1; may retain EGF in the endoplasmic reticulum and regulates its degradation through the endoplasmic reticulum-associated degradation (ERAD).

Subcellular location. Membrane.

Tissue specificity. Expressed in kidney, salivary gland, cerebrum and prostate.

Post-translational modifications. O-glycosylated with core 1-like and core 2-like glycans. It is uncertain if Ser-954 or Thr-955 is O-glycosylated. The modification here shows glycan heterogeneity: HexHexNAc (major) and Hex2HexNAc2 (minor).

Disease relevance. Hypomagnesemia 4 (HOMG4) [MIM:611718] A disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to moderate psychomotor retardation, and brisk tendon reflexes. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
P01133-1	1	yes
P01133-2	2
P01133-3	3

RefSeq proteins (4): NP_001171601, NP_001171602, NP_001343950, NP_001954* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000033	LDLR_classB_rpt	Repeat
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR016317	Pro-epidermal_GF	Family
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR049883	NOTCH1_EGF-like	Domain
IPR050778

Pfam: PF00008, PF00058, PF07645, PF14670

UniProt features (91 total): disulfide bond 27, sequence variant 15, domain 9, repeat 9, glycosylation site 9, strand 5, region of interest 4, chain 2, topological domain 2, splice variant 2, turn 2, signal peptide 1, compositionally biased region 1, transmembrane region 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
1NQL	X-RAY DIFFRACTION	2.8
1JL9	X-RAY DIFFRACTION	3
7SYD	ELECTRON MICROSCOPY	3.1
1IVO	X-RAY DIFFRACTION	3.3
7SYE	ELECTRON MICROSCOPY	3.3
7SZ0	ELECTRON MICROSCOPY	3.3
3NJP	X-RAY DIFFRACTION	3.3
8HGO	ELECTRON MICROSCOPY	3.31
7SZ1	ELECTRON MICROSCOPY	3.4
8HGS	ELECTRON MICROSCOPY	3.81
7OM4	X-RAY DIFFRACTION	6.05
1P9J	SOLUTION NMR
2KV4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01133-F1	70.66	0.21

Antibody-complex structures (SAbDab): 1 — 7OM4

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 (27): 318–330, 325–339, 341–354, 360–371, 367–380, 382–395, 401–412, 408–421, 423–436, 439–451, 447–461, 463–476, 745–756, 752–765, 767–780, 835–846, 840–855, 857–868, 874–888, 881–897 …

Glycosylation sites (9): 38, 104, 117, 148, 324, 404, 596, 815, 926

Function

Pathways and Gene Ontology

Reactome pathways

36 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-1227986	Signaling by ERBB2
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1236394	Signaling by ERBB4
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1251932	PLCG1 events in ERBB2 signaling
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-1963640	GRB2 events in ERBB2 signaling
R-HSA-1963642	PI3K events in ERBB2 signaling
R-HSA-212718	EGFR interacts with phospholipase C-gamma
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5637810	Constitutive Signaling by EGFRvIII
R-HSA-5638303	Inhibition of Signaling by Overexpressed EGFR
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6785631	ERBB2 Regulates Cell Motility
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847993	ERBB2 Activates PTK6 Signaling
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8863795	Downregulation of ERBB2 signaling
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9013507	NOTCH3 Activation and Transmission of Signal to the Nucleus
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9664565	Signaling by ERBB2 KD Mutants
R-HSA-9665348	Signaling by ERBB2 ECD mutants

MSigDB gene sets: 512 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, chr4q25, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_HINDBRAIN_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, REACTOME_GAB1_SIGNALOSOME, PID_TELOMERASE_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOCC_VACUOLAR_MEMBRANE

GO Biological Process (42): angiogenesis (GO:0001525), positive regulation of endothelial cell proliferation (GO:0001938), positive regulation of receptor internalization (GO:0002092), ubiquitin-dependent protein catabolic process (GO:0006511), epidermal growth factor receptor signaling pathway (GO:0007173), positive regulation of cell population proliferation (GO:0008284), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), positive regulation of peptidyl-threonine phosphorylation (GO:0010800), protein ubiquitination (GO:0016567), cerebellar granule cell precursor proliferation (GO:0021930), positive regulation of cerebellar granule cell precursor proliferation (GO:0021940), positive regulation of cell migration (GO:0030335), ERBB2-EGFR signaling pathway (GO:0038134), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), positive regulation of phosphorylation (GO:0042327), positive regulation of DNA binding (GO:0043388), positive regulation of MAPK cascade (GO:0043410), positive regulation of mitotic nuclear division (GO:0045840), positive regulation of DNA-templated transcription (GO:0045893), regulation of receptor signaling pathway via JAK-STAT (GO:0046425), branching morphogenesis of an epithelial tube (GO:0048754), epithelial cell proliferation (GO:0050673), negative regulation of secretion (GO:0051048), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), mammary gland alveolus development (GO:0060749), ubiquitin-dependent endocytosis (GO:0070086), ERK1 and ERK2 cascade (GO:0070371), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of calcium ion import (GO:0090279), negative regulation of cholesterol efflux (GO:0090370), positive regulation of hyaluronan biosynthetic process (GO:1900127), positive regulation of protein localization to early endosome (GO:1902966), positive regulation of epithelial tube formation (GO:1905278), regulation of protein localization to cell surface (GO:2000008), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060), cell population proliferation (GO:0008283), positive regulation of macromolecule metabolic process (GO:0010604), system development (GO:0048731), positive regulation of epithelial cell proliferation (GO:0050679)

GO Molecular Function (7): guanyl-nucleotide exchange factor activity (GO:0005085), epidermal growth factor receptor binding (GO:0005154), calcium ion binding (GO:0005509), growth factor activity (GO:0008083), transmembrane receptor protein tyrosine kinase activator activity (GO:0030297), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), clathrin-coated endocytic vesicle membrane (GO:0030669), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Signaling by ERBB2	5
Signaling by EGFR	5
Signaling by Receptor Tyrosine Kinases	3
Response to elevated platelet cytosolic Ca2+	1
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Signaling by EGFRvIII in Cancer	1
Signaling by Overexpressed Wild-Type EGFR in Cancer	1
MAPK1/MAPK3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epidermal growth factor receptor signaling pathway	2
signaling receptor activator activity	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
regulation of receptor internalization	1
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
ERBB signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of protein phosphorylation	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
protein modification by small protein conjugation	1
cell proliferation in external granule layer	1
cerebellar granule cell precursor proliferation	1
regulation of cerebellar granule cell precursor proliferation	1
positive regulation of neural precursor cell proliferation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
ERBB2 signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
phosphorylation	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1

Protein interactions and networks

STRING

8188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EGF	EGFR	P00533	999
EGF	ERBB2	P04626	998
EGF	ERBB3	P21860	998
EGF	AREG	P15514	997
EGF	ERBB4	Q15303	997
EGF	FGF7	P21781	993
EGF	GRB2	P29354	993
EGF	NTRK1	P04629	991
EGF	FGF8	P55075	991
EGF	FGF10	O15520	990
EGF	FGF4	P08620	989
EGF	FGF22	Q9HCT0	989
EGF	FGF6	P10767	989
EGF	HBEGF	Q99075	989
EGF	FGF18	O76093	989
EGF	FGF3	P11487	989
EGF	FGF5	P12034	989

IntAct

42 interactions, top by confidence:

A	B	Type	Score
EGF	EGFR	psi-mi:“MI:0407”(direct interaction)	0.970
EGFR	EGF	psi-mi:“MI:0407”(direct interaction)	0.970
EGFR	EGF	psi-mi:“MI:0915”(physical association)	0.970
EGF	EGFR	psi-mi:“MI:0915”(physical association)	0.970
EGFR	EGF	psi-mi:“MI:2364”(proximity)	0.970
EGF	MGST1	psi-mi:“MI:0915”(physical association)	0.560
APP	EGF	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (37): LMNA (Affinity Capture-Western), EGF (Co-localization), EGF (Co-localization), EGF (Co-localization), EGF (Affinity Capture-Luminescence), EGF (Co-crystal Structure), EGF (Co-crystal Structure), EGF (Reconstituted Complex), EGF (Reconstituted Complex), EGF (Reconstituted Complex), EGF (Co-localization), EGF (Co-localization), EGF (Affinity Capture-Western), EGF (Reconstituted Complex), EGF (Affinity Capture-Western)

ESM2 similar proteins: A0A2K5V015, A1YIY0, A8MUZ8, A8MWA4, B8JI71, O08569, P01133, P0DJ43, P14370, P14585, P17630, P19070, P48357, P82279, P97435, Q07444, Q0D2K5, Q28066, Q28660, Q29RU2, Q4KUS1, Q5G872, Q5R6R1, Q5RCW9, Q5T1H1, Q5UKY4, Q5Z5Q3, Q60736, Q63515, Q63722, Q6DFV8, Q6GMZ9, Q6V0K7, Q6ZN79, Q7TSY4, Q811Q4, Q8N2E2, Q8VHS2, Q90Y54, Q95MI4

Diamond homologs: A2AJ76, A2AR95, A2ARV4, A2VEC9, A4IHY6, A4QPB2, B3EWZ6, B4IXJ2, C0HL13, G3V928, O43897, O57460, O88307, P01130, P01131, P01133, P07225, P0DSP1, P10493, P13497, P14543, P15306, P20063, P27590, P35950, P35951, P35952, P53813, P86091, P98063, P98118, P98157, P98158, P98160, P98164, P98167, Q00918, Q00968, Q04833, Q07954

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
SLC34A2	down-regulates	EGF
EGF	up-regulates	ERBB2	binding
EGF	“up-regulates activity”	EGFR	binding
EGF	up-regulates	EGFR	binding
ADAM10	“up-regulates activity”	EGF	cleavage
EGF	“up-regulates quantity by expression”	HBB	“transcriptional regulation”
EGF	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	332
Likely benign	156
Benign	117

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
16614	NM_001963.6(EGF):c.3209C>T (p.Pro1070Leu)	Pathogenic
3065614	NM_001963.6(EGF):c.1189+1G>A	Likely pathogenic

SpliceAI

4540 predictions. Top by Δscore:

Variant	Effect	Δscore
4:109943366:GAAA:G	donor_gain	1.0000
4:109944000:G:GT	donor_gain	1.0000
4:109945100:T:A	acceptor_gain	1.0000
4:109960990:G:GG	donor_gain	1.0000
4:109961859:TTAG:T	acceptor_loss	1.0000
4:109961861:A:AG	acceptor_gain	1.0000
4:109961861:A:G	acceptor_loss	1.0000
4:109961862:G:C	acceptor_loss	1.0000
4:109961862:G:GA	acceptor_gain	1.0000
4:109961862:GA:G	acceptor_gain	1.0000
4:109961862:GAA:G	acceptor_gain	1.0000
4:109961862:GAAC:G	acceptor_gain	1.0000
4:109961862:GAACT:G	acceptor_gain	1.0000
4:109961880:C:CA	acceptor_gain	1.0000
4:109961983:GCG:G	donor_gain	1.0000
4:109961984:CGGT:C	donor_loss	1.0000
4:109961985:GGTG:G	donor_loss	1.0000
4:109961986:G:GA	donor_loss	1.0000
4:109961986:G:GG	donor_gain	1.0000
4:109961987:TGAG:T	donor_loss	1.0000
4:109961988:GAGT:G	donor_loss	1.0000
4:109963169:GTA:G	acceptor_loss	1.0000
4:109963171:A:AG	acceptor_gain	1.0000
4:109963172:G:A	acceptor_loss	1.0000
4:109963172:G:GG	acceptor_gain	1.0000
4:109963172:GGTT:G	acceptor_gain	1.0000
4:109963295:TCAGG:T	donor_loss	1.0000
4:109963296:CAGGT:C	donor_loss	1.0000
4:109963297:AGGTT:A	donor_loss	1.0000
4:109963298:GGT:G	donor_loss	1.0000

AlphaMissense

7943 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:109960911:T:A	C371S	0.989
4:109960912:G:C	C371S	0.989
4:109999707:T:A	C1012S	0.988
4:109999708:G:C	C1012S	0.988
4:109960983:T:A	C395S	0.985
4:109960984:G:C	C395S	0.985
4:109960878:T:A	C360S	0.983
4:109960879:G:C	C360S	0.983
4:109960899:T:A	C367S	0.982
4:109960900:G:C	C367S	0.982
4:109980010:T:A	W698R	0.982
4:109980010:T:C	W698R	0.982
4:109960956:T:C	F386L	0.981
4:109960958:T:A	F386L	0.981
4:109960958:T:G	F386L	0.981
4:109979995:T:C	F693L	0.981
4:109979997:T:A	F693L	0.981
4:109979997:T:G	F693L	0.981
4:109960940:C:G	C380W	0.980
4:109976154:T:A	W658R	0.980
4:109976154:T:C	W658R	0.980
4:109976187:G:C	A669P	0.979
4:109960944:T:C	C382R	0.978
4:109976151:T:G	Y657D	0.978
4:109960938:T:A	C380S	0.976
4:109960939:G:C	C380S	0.976
4:109994825:T:A	C984S	0.975
4:109994826:G:C	C984S	0.975
4:109994876:T:A	C1001S	0.975
4:109994877:G:C	C1001S	0.975

dbSNP variants (sampled 300 via entrez): RS1000012351 (4:110009393 G>A), RS1000060525 (4:109914978 G>A,T), RS1000083582 (4:109970686 C>A,T), RS1000128057 (4:110009687 A>G), RS1000132511 (4:109971136 TCAA>T), RS1000143949 (4:109997170 G>A,T), RS1000177080 (4:109997460 T>A,G), RS1000181928 (4:109911535 C>T), RS1000190490 (4:109920687 T>A), RS10002835 (4:109927648 C>G,T), RS10002971 (4:109974894 A>C), RS1000322480 (4:109945642 G>A,T), RS1000328296 (4:109990392 A>T), RS1000363853 (4:109934212 A>G), RS1000480879 (4:109995171 T>G)

Disease associations

OMIM: gene MIM:131530 | disease phenotypes: MIM:611718

GenCC curated gene-disease

Disease	Classification	Inheritance
familial primary hypomagnesemia with normocalciuria and normocalcemia	Supportive	Autosomal dominant
renal hypomagnesemia 4	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
renal hypomagnesemia 4	Limited	AR

Mondo (4): renal hypomagnesemia 4 (MONDO:0012717), cholangiocarcinoma (MONDO:0019087), hereditary renal cell carcinoma (MONDO:0003008), familial primary hypomagnesemia with normocalciuria and normocalcemia (MONDO:0018101)

Orphanet (2): OBSOLETE: Familial primary hypomagnesemia with normocalciuria and normocalcemia (Orphanet:34527), Cholangiocarcinoma (Orphanet:70567)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0002342	Moderate intellectual disability
HP:0002917	Hypomagnesemia

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000519_8	Hair morphology	9.000000e-06
GCST004603_270	Platelet count	3.000000e-16
GCST004607_224	Plateletcrit	8.000000e-19
GCST004619_33	Reticulocyte fraction of red cells	5.000000e-10
GCST004622_166	Reticulocyte count	3.000000e-10
GCST005987_34	Albumin-globulin ratio	2.000000e-11
GCST005990_47	Non-albumin protein levels	2.000000e-10
GCST005991_81	Platelet count	2.000000e-28
GCST006011_25	Mean corpuscular volume	7.000000e-10
GCST006585_1646	Blood protein levels	5.000000e-62
GCST008159_73	Waist-to-hip ratio adjusted for BMI	1.000000e-06
GCST012032_2	Platelet count	3.000000e-09
GCST90002385_256	High light scatter reticulocyte count	2.000000e-13
GCST90002386_3	High light scatter reticulocyte percentage of red cells	2.000000e-12
GCST90002388_352	Lymphocyte count	6.000000e-20
GCST90002391_22	Mean corpuscular hemoglobin concentration	3.000000e-17
GCST90002393_136	Monocyte count	2.000000e-18
GCST90002394_63	Monocyte percentage of white cells	3.000000e-09
GCST90002397_20	Mean spheric corpuscular volume	9.000000e-33
GCST90002399_382	Neutrophil percentage of white cells	1.000000e-11
GCST90002400_437	Plateletcrit	2.000000e-36
GCST90002400_438	Plateletcrit	4.000000e-10
GCST90002401_150	Platelet distribution width	1.000000e-18
GCST90002402_743	Platelet count	3.000000e-27
GCST90002405_41	Reticulocyte count	3.000000e-18
GCST90002406_92	Reticulocyte fraction of red cells	4.000000e-17
GCST90016667_28	Spleen volume	4.000000e-14

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0005038	hair morphology
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0005128	albumin:globulin ratio measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004587	lymphocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007984	platelet component distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018281	Cholangiocarcinoma	C04.557.470.200.025.450
C536851	Familial renal cell carcinoma (supp.)
C567127	Hypomagnesemia 4, Renal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5734 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
EGF EXPRESSION	Cetuximab	Head And Neck Squamous Cell Carcinoma	Resistance	CIViC D	EID826

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4444903	Efficacy	3	cetuximab	Colorectal Neoplasms;Rectal Neoplasms

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs929446	EGF		0.00	0
rs2074390	EGF		0.00	0
rs4444903	EGF	3	3.25	1	cetuximab
rs4698803	EGF		0.00	0
rs6533485	EGF		0.00	0
rs6850557	EGF		0.00	0
rs11568972	EGF		0.00	0
rs11568993	EGF		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
U 0126	decreases reaction, increases expression, increases secretion, decreases response to substance, increases reaction (+2 more)	15
RTKI cpd	decreases secretion, increases secretion, increases reaction, affects localization, decreases reaction (+5 more)	14
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases secretion, decreases activity, decreases secretion (+3 more)	13
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases activity, increases secretion, increases reaction (+4 more)	12
Gefitinib	increases abundance, affects localization, decreases reaction, affects binding, increases reaction (+3 more)	10
Quercetin	increases secretion, decreases expression, decreases phosphorylation, decreases reaction, increases response to substance (+2 more)	8
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	affects localization, decreases reaction, increases activity, increases expression, increases phosphorylation	7
Estradiol	increases reaction, increases phosphorylation, affects activity, affects cotreatment, decreases reaction (+2 more)	7
Valproic Acid	affects cotreatment, decreases expression, decreases reaction, increases activity, increases reaction (+2 more)	6
Erlotinib Hydrochloride	increases phosphorylation, affects binding, decreases reaction, decreases response to substance, increases reaction (+1 more)	5
Resveratrol	increases reaction, decreases phosphorylation, increases phosphorylation, affects reaction, decreases activity (+5 more)	5
Luteolin	decreases phosphorylation, decreases reaction, increases expression, increases reaction, increases phosphorylation (+2 more)	5
sodium arsenite	decreases reaction, increases phosphorylation, increases reaction, decreases expression, increases expression	4
epigallocatechin gallate	affects binding, decreases reaction, increases reaction, increases activity, increases expression (+2 more)	4
pyrazolanthrone	decreases response to substance, increases reaction, decreases reaction, increases expression, increases secretion	4
Acetylcysteine	increases expression, affects cotreatment, increases secretion, decreases expression, decreases reaction	4
Curcumin	increases expression, increases phosphorylation, increases secretion, decreases activity, decreases reaction	4
trichostatin A	affects cotreatment, decreases expression	3
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression, affects cotreatment, affects binding, decreases reaction, increases phosphorylation	3
AG 1879	affects cotreatment, decreases reaction, increases expression, increases phosphorylation	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, decreases reaction, decreases response to substance, increases reaction (+1 more)	3
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases reaction, increases phosphorylation	3
Fulvestrant	affects activity, affects cotreatment, decreases reaction, increases expression	3
Lipopolysaccharides	decreases reaction, increases secretion, affects cotreatment, affects response to substance, increases expression	3
Tamoxifen	decreases response to substance, increases activity, increases response to substance, decreases reaction, affects activity (+2 more)	3
Tetrachlorodibenzodioxin	affects binding, decreases reaction, increases expression	3
Tretinoin	decreases activity, affects cotreatment, increases expression	3
nonachlor	affects binding, affects cotreatment, decreases reaction, increases phosphorylation	2
triphenyl phosphate	affects expression, increases expression	2
bisphenol A	increases secretion, decreases expression, increases expression	2

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1031405	Binding	Inhibition of human EGF at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9DY	A31-IS11 EGF-2	Spontaneously immortalized cell line	Sex unspecified
CVCL_A9DZ	LA9-IS11 EGF-2	Spontaneously immortalized cell line	Male
CVCL_B1QS	Abcam HeLa EGF KO	Cancer cell line	Female
CVCL_B8F2	Abcam HCT 116 EGF KO	Cancer cell line	Male
CVCL_B8V4	Abcam MCF-7 EGF KO	Cancer cell line	Female
CVCL_B9HA	Abcam A-549 EGF KO	Cancer cell line	Male
CVCL_D7P7	Ubigene A-549 EGF KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00168987	PHASE4	COMPLETED	Influence of an Oral Nutritional Supplement Rich in Omega-3 Fatty Acids on Functional State and Quality of Life in Malnourished Patients With Gastroenterological Tumors
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00797121	PHASE4	UNKNOWN	Preoperative Biliary Drainage for Resectable Hilar Cholangiocarcinoma
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01256047	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Hepatectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02174575	PHASE4	WITHDRAWN	Anesthetic Agents and Acute Kidney Injury After Liver Resection Surgery
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT00540735	PHASE3	TERMINATED	Efficiency Evaluation of Photodynamic Therapy With Photofrin® on Unresectable Type III or IV Cholangiocarcinomas
NCT00653978	PHASE3	UNKNOWN	Unilateral Versus Bilateral Stents for Bismuth Type II and III Malignant Hilar Strictures
NCT00809081	PHASE3	UNKNOWN	Early Enteral Feeding After Pylorus Preserving Pancreatoduodenectomy
NCT00869635	PHASE3	COMPLETED	S-1 and Photodynamic Therapy in Cholangiocarcinoma
NCT00907413	PHASE3	TERMINATED	Photodynamic Therapy (PDT) Trial for Palliation of Cholangiocarcinoma
NCT01926236	PHASE3	COMPLETED	Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers
NCT02170090	PHASE3	ACTIVE_NOT_RECRUITING	Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
NCT02548195	PHASE3	UNKNOWN	Oxaliplatin+Gemcitabine vs Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma
NCT02773485	PHASE3	UNKNOWN	Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma
NCT02853474	PHASE3	COMPLETED	Early Palliative Care in Patients With Metastatic Upper Gastrointestinal Cancers Treated With First-line Chemotherapy
NCT02989857	PHASE3	COMPLETED	Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)
NCT03656536	PHASE3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma
NCT03773302	PHASE3	TERMINATED	Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
NCT03779035	PHASE3	UNKNOWN	Adjuvant Chemotherapy for Biliary Tract Cancer After Curative Resection
NCT04093362	PHASE3	TERMINATED	Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements
NCT04157985	PHASE3	COMPLETED	Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
NCT05823311	PHASE3	RECRUITING	Lenvatinib, Tislelizumab Combined with Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma
NCT05876754	PHASE3	RECRUITING	An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
NCT05948475	PHASE3	RECRUITING	Study of Tinengotinib VS. Physician’s Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma
NCT07155525	PHASE3	RECRUITING	Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas
NCT07328919	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations
NCT00286013	PHASE2	COMPLETED	Feasibility of Radiotherapy and Concomitant Gemcitabine and Oxaliplatin in Locally Advanced Pancreatic Cancer and Distal Cholangiocarcinoma
NCT00290316	PHASE2	UNKNOWN	Accuracy of Endoscopic Ultrasound for Detection of Tumors of the Liver
NCT00350753	PHASE2	COMPLETED	Avastin and Tarceva for Upper Gastrointestinal Cancers
NCT00356161	PHASE2	UNKNOWN	HAI Via Interventionally Implanted Port Catheter Systems
NCT00660140	PHASE2	COMPLETED	Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer
NCT00713687	PHASE2	WITHDRAWN	Gemcitabine/Oxaliplatin and Photodynamic Therapy in Cholangiocarcinoma
NCT00779454	PHASE2	COMPLETED	Combined Biological Treatment and Chemotherapy for Patients With Inoperable Cholangiocarcinoma
NCT00832637	PHASE2	TERMINATED	Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers
NCT00948935	PHASE2	COMPLETED	Study of Gemcitabine, Irinotecan and Panitumumab in Patients With Advanced and Metastatic Biliary Tract Adenocarcinoma