AREG

Summary

AREG (amphiregulin, HGNC:651) is a protein-coding gene on chromosome 4q13.3, encoding Amphiregulin (P15514). Ligand of the EGF receptor/EGFR. In precision oncology, AREG Expression confers sensitivity to Panitumumab in Colorectal Cancer (CIViC Level B); 3 further curated variant–drug associations are listed below. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a member of the epidermal growth factor family. It is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells and fibroblasts. It is related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). The protein interacts with the EGF/TGF-alpha receptor to promote the growth of normal epithelial cells, and it inhibits the growth of certain aggressive carcinoma cell lines. It also functions in mammary gland, oocyte and bone tissue development. This gene is associated with a psoriasis-like skin phenotype, and is also associated with other pathological disorders, including various types of cancers and inflammatory conditions.

Source: NCBI Gene 374 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Kennedy disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 17
• Clinical variants (ClinVar): 1,116 total — 251 pathogenic, 109 likely-pathogenic
• Druggable target: yes
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001657

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:651
Approved symbol	AREG
Name	amphiregulin
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	AR, CRDGF
Ensembl gene	ENSG00000109321
Ensembl biotype	protein_coding
OMIM	104640
Entrez	374

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000395748, ENST00000502307, ENST00000511560, ENST00000953445

RefSeq mRNA: 1 — MANE Select: NM_001657 NM_001657

CCDS: CCDS3565

Canonical transcript exons

ENST00000395748 — 6 exons

Exon	Start	End
ENSE00001522686	74454759	74455005
ENSE00001826979	74445136	74445406
ENSE00002443152	74449047	74449248
ENSE00002449861	74452544	74452655
ENSE00002506705	74446534	74446782
ENSE00003635241	74450380	74450532

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.7550 / max 5068.0649, expressed in 1038 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
203221	93.9043	1024
203233	0.2773	136
203223	0.2595	137
203225	0.1780	80
203222	0.0792	32
203224	0.0390	15
203241	0.0178	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of urinary bladder	UBERON:0001259	98.14	gold quality
endometrium epithelium	UBERON:0004811	97.25	gold quality
right lung	UBERON:0002167	96.24	gold quality
gluteal muscle	UBERON:0002000	95.88	gold quality
gall bladder	UBERON:0002110	94.07	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.87	gold quality
cervix squamous epithelium	UBERON:0006922	90.72	gold quality
amniotic fluid	UBERON:0000173	90.63	gold quality
placenta	UBERON:0001987	90.50	gold quality
esophagus squamous epithelium	UBERON:0006920	90.41	gold quality
esophagus mucosa	UBERON:0002469	89.73	gold quality
upper lobe of left lung	UBERON:0008952	89.49	gold quality
upper lobe of lung	UBERON:0008948	89.17	gold quality
squamous epithelium	UBERON:0006914	88.70	gold quality
epithelium of esophagus	UBERON:0001976	88.67	gold quality
cervix epithelium	UBERON:0004801	88.33	gold quality
rectum	UBERON:0001052	88.28	gold quality
left uterine tube	UBERON:0001303	87.99	gold quality
buccal mucosa cell	CL:0002336	87.41	gold quality
omental fat pad	UBERON:0010414	87.21	gold quality
peritoneum	UBERON:0002358	87.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.06	gold quality
gingival epithelium	UBERON:0001949	84.99	gold quality
lower lobe of lung	UBERON:0008949	84.83	gold quality
vermiform appendix	UBERON:0001154	84.69	gold quality
mucosa of stomach	UBERON:0001199	84.12	gold quality
lower esophagus mucosa	UBERON:0035834	84.03	gold quality
lung	UBERON:0002048	83.90	gold quality
mucosa of transverse colon	UBERON:0004991	83.83	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	14831.48
E-MTAB-10855	yes	12845.91
E-MTAB-10885	yes	11316.14
E-CURD-46	yes	8479.43
E-CURD-126	yes	6832.49
E-HCAD-24	yes	6676.22
E-MTAB-6653	yes	6040.99
E-MTAB-8884	yes	5742.09
E-MTAB-9435	yes	4700.31
E-CURD-88	yes	4311.55
E-GEOD-149689	yes	2204.26
E-GEOD-76312	yes	279.39
E-MTAB-6701	yes	123.42
E-MTAB-8142	yes	69.69
E-HCAD-4	yes	42.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AGR2, AHR, AP1, AR, BRCA1, CREB1, DMTF1, EGR1, ESR1, F2RL1, JUN, NFIL3, SATB1, SP1, TP53, WT1

miRNA regulators (miRDB)

35 targeting AREG, 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-190A-3P	100.00	80.35	5520
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-640	98.44	66.93	644
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• (TARP) expression in prostate cancer cells leads to an increased growth rate and induction of caveolins and amphiregulin. (PMID:11719440)
• mRNA expression in atrophic gastritis before and after Helicobacter pylori eradication (PMID:11859273)
• H358 cells secrete a high level of amphiregulin that, in combination with IGF1, prevents serum deprivation apoptosis (PMID:12356750)
• Review. The activation of EGFR in response to smoke involves cleavage of amphiregulin by ADAM 17. (PMID:12568494)
• amphiregulin binds to EGF receptor and has a role in stimulation of lung epithelial cells upon exposure to tobacco smoke (PMID:12711607)
• Data show that in squamous cell carcinoma cells, stimulation with G protein-coupled receptor agonists specifically results in cleavage and release of amphiregulin (AR) by TACE. (PMID:12743035)
• Amphiregulin(AR) overexpressing cells (HaCaT-AR) displayed autonomous proliferation in serum-free media. HaCaT-AR cells formed rapidly growing tumors with AR expression similar to keratoacanthoma. (PMID:14633617)
• epidermal AR expression as a possible mediator of innate cutaneous immunity and epidermal proliferation and also as a potential trigger of both cutaneous psoriasis and psoriatic arthritis. (PMID:15186320)
• amphiregulin- and ErbB1-dependent mechanism by which autocrine ERK activation is maintained in normal keratinocytes (PMID:15254267)
• AR is under strong regulation by the cAMP pathway in various cell types (PMID:15284208)
• upregulation of the epiregulin and amphiregulin expression is part of the signal transduction pathway which leads to ovulation and luteinization in the human ovary (PMID:15474502)
• an early-response growth factor that may contribute to the initial phases of liver regeneration. (PMID:15685553)
• Amphiregulin was secreted by human mast cells after aggregation of FcepsilonRI. Amphiregulin may be new target molecule for treatment of overproduction of sputum in bronchial asthma. (PMID:15696081)
• Mast cells secreted amphiregulin on IgE cross-linking, and amphiregulin induced proliferation of lung fibroblasts. Local release of amphiregulin by mast cells could play role in lung fibrosis by promoting proliferation of lung fibroblasts. (PMID:15696083)
• AREG gene expressed by purified primary myeloma cells, and expression higher than in normal bone marrow (BM) plasma cells or plasmablastic cells; AREG plays an important role in biology of multiple myeloma (PMID:15735670)
• AR and IGF1 cooperate to prevent apoptosis by activating a specific PKC-p90(rsk)-dependent pathway, which leads to Bad and Bax inactivation. (PMID:15767261)
• Enhanced transmigration of human neutrophils through polarized epithelial cell monolayers of MDCK cells after administration of AR, further supporting aspecific role for AR in pathogenesis of psoriasis. (PMID:15955087)
• Data suggest that parathyroid hormone-induced amphiregulin mRNA expression is mediated primarily through cyclic AMP-protein kinase A-CREB signaling. (PMID:16088955)
• Results suggest that hypoxia promotes intestinal epithelial amphiregulin expression in a CREB-dependent manner, an event that may contribute to increased proliferation. (PMID:16207795)
• The mechanism of deoxycholic acid-induced epideermal growth factor receptor activation is ligand-dependent and is controlled, at least in part, at the level of amphiregulin release from the basolateral cell membrane. (PMID:16213893)
• HAT induces amphiregulin production through the PAR-2 mediated ERK pathway, and then causes amphiregulin release by a TACE-dependent mechanism (PMID:16336275)
• Amphiregulin and HB-EGF mediate retinoic acid-mediated epidermal hyperplasia (PMID:16470170)
• results show that TACE undergoes phosphorylation that regulates release of amphiregulin upon GRP treatment; a signaling cascade of GRP-Src-PI3-K-PDK1-TACE-amphiregulin-EGFR with multiple points of interaction, translocation & phosphorylation is suggested (PMID:16641105)
• findings demonstrated that PGE2 may mimic LH action at least in part by the activation of amphiregulin and epiregulin biosynthesis in human granulosa cells (PMID:16888076)
• Amphiregulin (AR) up-regulates a number of genes involved in cell motility and invasion in MCF10A cells, suggesting that an AR autocrine loop contributes to the aggressive breast cancer phenotype. (PMID:17035230)
• AREG is up-regulated in tumor cells of SCC but not BCC of the skin. AREG is also overexpressed in asymptomatic epidermis adjacent to both SCC and BCC, relative to normal skin. (PMID:17525275)
• MIP-3alpha-mediated ERK1/2 activation in Caco-2 cells appeared to require metalloproteinase-dependent release of the endogenous EGFR ligand amphiregulin and transactivation of the EGFR. (PMID:17548638)
• After exposure to cisplatin, the resistant breast cancer cells secrete amphiregulin protein by short interfering RNA resulting in a nearly complete reversion of the resistant phenotype. (PMID:17942395)
• TNFalpha may play a key role in cooperation with HB-EGF and AREG in the proliferation of epidermal keratinocytes at the psoriatic skin lesions. (PMID:17960400)
• AREG is preferentially expressed in breast tumors co-expressing HER2/HER4. AREG is associated with estradiol receptors, small tumour size, low histoprognostic grading, high HER4 levels. (PMID:17962208)
• amphiregulin-specific EGF-R fate results from decreased hSprouty2 degradation and reduced Cbl recruitment to underphosphorylated EGF-R, two effects that impair EGF-R trafficking to lysosomes (PMID:18045238)
• Amphiregulin was expressed most dominantly among EGF receptor ligands tested and may mediate the hCG signal in human oocyte maturation. Elaborate interaction between AR and hCG may be required for an optimal oocyte maturation. (PMID:18325497)
• The expression of amphiregulin was increased in the secretory phase of human endometrium, and may play an important role in human implantation. (PMID:18560449)
• serum amphiregulin in patients with advanced non-squamous, non-small cell lung cancer (PMID:18811692)
• Amphiregulin has a protective effect against apoptosis in the human corpus luteum. (PMID:18835871)
• plasma-membrane-anchored growth factor pro-amphiregulin binds A-type lamin and regulates global transcription (PMID:18946024)
• interleukin-4 and amphiregulin have roles in the proliferation of human airway smooth muscle cells and cytokine release (PMID:18955794)
• Amphiregulin plays a crucial role in UV-induced EGFR activation and is overexpressed in skin cancer cell lines (PMID:19003995)
• Use of AREG as a biomarker in non-small cell lung cancershould be encouraged since AREG is correlated with a poor prognosis, resistance to treatments and to apoptosis. (PMID:19070973)
• These findings suggest that mitochondrial dysfunction induced Ca(2+) mobilization, and reactive oxygen species overproduction, which modulated the chemo-resistance and migration of hepatoma cells through the induction and activation of amphiregulin. (PMID:19337692)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Areg	ENSMUSG00000029378
rattus_norvegicus	Areg	ENSRNOG00000002754

Paralogs (5): HBEGF (ENSG00000113070), EREG (ENSG00000124882), TGFA (ENSG00000163235), BTC (ENSG00000174808), EPGN (ENSG00000182585)

Protein

Protein identifiers

Amphiregulin — P15514 (reviewed: P15514)

Alternative names: Colorectum cell-derived growth factor

All UniProt accessions (2): P15514, D6RFX5

UniProt curated annotations — full annotation on UniProt →

Function. Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts.

Subunit / interactions. The immature precursor interacts with CNIH.

Subcellular location. Membrane.

Induction. By phorbol 12-myristate 13-acetate (PMA).

Miscellaneous. AR is a protein containing cysteines in disulfide linkage(s) that are essential for its biological activity. AR may contain oligosaccharides and/or lipid moieties that are not obligatory for the biological activity.

Similarity. Belongs to the amphiregulin family.

RefSeq proteins (1): NP_001648* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain

UniProt features (25 total): compositionally biased region 3, glycosylation site 3, disulfide bond 3, strand 3, propeptide 2, sequence variant 2, turn 2, region of interest 2, signal peptide 1, chain 1, helix 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2RNL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15514-F1	68.00	0.18

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): 146–159, 154–170, 172–181

Glycosylation sites (3): 30, 113, 119

Function

Pathways and Gene Ontology

Reactome pathways

45 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-204005	COPII-mediated vesicle transport
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-5694530	Cargo concentration in the ER
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
R-HSA-9818030	NFE2L2 regulating tumorigenic genes
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-1643713	Signaling by EGFR in Cancer
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-2262752	Cellular responses to stress
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation

MSigDB gene sets: 1019 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, ATF_B, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_SINGLE_FERTILIZATION, BROWNE_HCMV_INFECTION_4HR_UP, MODULE_92, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, FARMER_BREAST_CANCER_CLUSTER_7

GO Biological Process (19): epidermal growth factor receptor signaling pathway (GO:0007173), G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), positive regulation of keratinocyte proliferation (GO:0010838), glial cell proliferation (GO:0014009), neuron projection development (GO:0031175), response to estradiol (GO:0032355), ERBB2-EGFR signaling pathway (GO:0038134), positive regulation of phosphorylation (GO:0042327), response to hydrogen peroxide (GO:0042542), response to peptide hormone (GO:0043434), negative regulation of osteoblast differentiation (GO:0045668), response to glucocorticoid (GO:0051384), response to cAMP (GO:0051591), dichotomous subdivision of terminal units involved in mammary gland duct morphogenesis (GO:0060598), mammary gland branching involved in thelarche (GO:0060744), mammary gland alveolus development (GO:0060749), epithelial cell proliferation involved in mammary gland duct elongation (GO:0060750)

GO Molecular Function (6): cytokine activity (GO:0005125), epidermal growth factor receptor binding (GO:0005154), 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 (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), endoplasmic reticulum membrane (GO:0005789), cell surface (GO:0009986), ER to Golgi transport vesicle membrane (GO:0012507), clathrin-coated endocytic vesicle membrane (GO:0030669), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Signaling by EGFR	5
ER to Golgi Anterograde Transport	2
Developmental Lineages of the Mammary Gland	2
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
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
response to oxygen-containing compound	3
signal transduction	2
cell population proliferation	2
branch elongation involved in mammary gland duct branching	2
receptor ligand activity	2
signaling receptor activator activity	2
ERBB signaling pathway	1
G protein-coupled receptor activity	1
cell communication	1
signaling	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
positive regulation of epithelial cell proliferation	1
gliogenesis	1
neuron development	1
plasma membrane bounded cell projection organization	1
response to lipid	1
epidermal growth factor receptor signaling pathway	1
ERBB2 signaling pathway	1
phosphorylation	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1
response to reactive oxygen species	1
response to hormone	1
response to nitrogen compound	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
response to corticosteroid	1
response to purine-containing compound	1
response to organophosphorus	1
dichotomous subdivision of an epithelial terminal unit	1
thelarche	1
branching involved in mammary gland duct morphogenesis	1
anatomical structure development	1
mammary gland lobule development	1
mammary gland epithelial cell proliferation	1

Protein interactions and networks

STRING

2691 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AREG	EGF	P01133	997
AREG	EGFR	P00533	996
AREG	EREG	O14944	995
AREG	BTC	P35070	986
AREG	ERBB3	P21860	981
AREG	ERBB4	Q15303	978
AREG	TGFA	P01135	934
AREG	ERBB2	P04626	888
AREG	ICAM1	P05362	886
AREG	EPGN	Q6UW88	884
AREG	NRG1	P98202	770
AREG	LHCGR	P22888	766
AREG	NRG2	O14511	742
AREG	ANGPTL4	Q9BY76	725
AREG	NRG4	Q8WWG1	725

IntAct

31 interactions, top by confidence:

A	B	Type	Score
S100A4	AREG	psi-mi:“MI:0407”(direct interaction)	0.680
AREG		psi-mi:“MI:0915”(physical association)	0.560
	AREG	psi-mi:“MI:0915”(physical association)	0.560
AREG	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	AREG	psi-mi:“MI:0915”(physical association)	0.560
AREG	ADCY9	psi-mi:“MI:0914”(association)	0.530
AREG	E2	psi-mi:“MI:0915”(physical association)	0.490
AREG	EGFR	psi-mi:“MI:0407”(direct interaction)	0.440
S100A2	AREG	psi-mi:“MI:0407”(direct interaction)	0.440
S100A5	AREG	psi-mi:“MI:0407”(direct interaction)	0.440
	TMEM223	psi-mi:“MI:0914”(association)	0.350
FOXA1	AREG	psi-mi:“MI:0914”(association)	0.350
CCND3	AREG	psi-mi:“MI:2364”(proximity)	0.270
AREG	E2	psi-mi:“MI:0915”(physical association)	0.000
AREG	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
AREG	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
AREG	ptsA	psi-mi:“MI:0915”(physical association)	0.000
AREG	UBQLN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): KRTAP10-3 (Two-hybrid), ADCY9 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), AREG (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), AREG (Co-localization), AREG (Affinity Capture-MS), ADCY9 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), SNX11 (Affinity Capture-MS), KRTAP10-8 (Two-hybrid), CYSRT1 (Two-hybrid), AREG (Affinity Capture-MS), AREG (Reconstituted Complex), ADCY9 (Affinity Capture-MS)

ESM2 similar proteins: A1A4K1, B1H3G4, E9PV24, O35988, O61704, O75167, O93383, P14209, P14599, P15514, P24338, P31431, P31955, P34741, P34900, P34901, P43322, P43407, P49414, P49416, P50605, P55808, P58239, Q02297, Q0VFF9, Q1RMT9, Q27913, Q56A20, Q58DD4, Q5RAT9, Q5RCS3, Q5RE35, Q5REP3, Q5XG99, Q6DBW9, Q6GR51, Q6PKG0, Q6ZQ58, Q7SXB3, Q7TMJ8

Diamond homologs: A0A6G9KJM3, O14944, P01134, P01135, P0DQX9, P0DSL4, P15514, P24338, P31955, P35070, P48030, P55244, P98135, P98138, Q01580, Q05928, Q06175, Q06186, Q06922, Q09118, Q17QD6, Q5EG71, Q61521, Q6PFE7, Q8IYR6, Q99075, Q9J524, Q9QYM9, Q9QYV1, Q9TTC5, Q9UIK5, Q9W7C5, Q9Z0L5, A0A7H0DMZ6, O57166, P01136, P0DOP9, P0DOQ0, P20494, Q6RZT5

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
AREG	up-regulates	EGFR	binding
SRC	up-regulates	AREG	cleavage
WT1	“up-regulates quantity by expression”	AREG	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	AREG	“transcriptional regulation”
SATB1	“down-regulates quantity by repression”	AREG	“transcriptional regulation”
ADAM17	“up-regulates activity”	AREG	cleavage
AREG	up-regulates	ERBB2	phosphorylation
AREG	“up-regulates activity”	EGFR	binding
DMTF1	“up-regulates quantity by expression”	AREG	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1116 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	251
Likely pathogenic	109
Uncertain significance	227
Likely benign	288
Benign	107

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068775	NM_000044.6(AR):c.2225G>T (p.Trp742Leu)	Pathogenic
1071361	NC_000023.10:g.(?66905832)(66905988_?)del	Pathogenic
1071362	NC_000023.10:g.(?66863078)(66943703_?)del	Pathogenic
1072748	NM_000044.6(AR):c.1737del (p.Cys580fs)	Pathogenic
1076800	NM_000044.6(AR):c.1063G>T (p.Glu355Ter)	Pathogenic
1202584	NM_000044.6(AR):c.2607+2T>G	Pathogenic
1202585	NM_000044.6(AR):c.2657A>T (p.His886Leu)	Pathogenic
1244244	NM_000044.6(AR):c.2486A>T (p.Asp829Val)	Pathogenic
1298359	NM_000044.6(AR):c.2255G>A (p.Trp752Ter)	Pathogenic
1298364	NM_000044.6(AR):c.1567G>T (p.Glu523Ter)	Pathogenic
1298367	NM_000044.6(AR):c.175C>T (p.Gln59Ter)	Pathogenic
1338498	NM_000044.6(AR):c.675_678del (p.Asn224_Tyr225insTer)	Pathogenic
1341693	NM_000044.6(AR):c.2226G>A (p.Trp742Ter)	Pathogenic
1342730	NM_000044.6(AR):c.2494C>T (p.Arg832Ter)	Pathogenic
1344487	NM_000044.6(AR):c.2126G>A (p.Gly709Glu)	Pathogenic
1344505	NM_000044.6(AR):c.2407dup (p.Gln803fs)	Pathogenic
1394063	NM_000044.6(AR):c.2319_2321dup (p.Tyr774Ter)	Pathogenic
1410848	NM_000044.6(AR):c.1477C>T (p.Gln493Ter)	Pathogenic
1421027	NM_000044.6(AR):c.358C>T (p.Gln120Ter)	Pathogenic
1437090	NM_000044.6(AR):c.1885+2T>G	Pathogenic
1454388	NC_000023.10:g.(?66941655)(66943683_?)del	Pathogenic
1454419	NM_000044.6(AR):c.1707del (p.Cys570fs)	Pathogenic
1454671	NM_000044.6(AR):c.829_833dup (p.Val279fs)	Pathogenic
1455502	NM_000044.6(AR):c.2512G>T (p.Glu838Ter)	Pathogenic
1460010	NC_000023.10:g.(?66931224)(66931551_?)del	Pathogenic
1460367	NM_000044.6(AR):c.2515C>A (p.Leu839Ile)	Pathogenic
1470535	NM_000044.6(AR):c.1A>T (p.Met1Leu)	Pathogenic
151774	GRCh38/hg38 Xq12(chrX:67532311-68353901)x1	Pathogenic
1518028	NM_000044.6(AR):c.2750del (p.Phe917fs)	Pathogenic
1526808	GRCh37/hg19 Xq12-13.1(chrX:65734663-68081523)	Pathogenic

SpliceAI

575 predictions. Top by Δscore:

Variant	Effect	Δscore
4:74446518:A:AG	acceptor_gain	1.0000
4:74446519:T:G	acceptor_gain	1.0000
4:74446528:CTGCA:C	acceptor_loss	1.0000
4:74446529:T:A	acceptor_gain	1.0000
4:74446529:TGCA:T	acceptor_loss	1.0000
4:74446530:GCA:G	acceptor_loss	1.0000
4:74446531:CAG:C	acceptor_loss	1.0000
4:74446532:A:AG	acceptor_gain	1.0000
4:74446532:AG:A	acceptor_gain	1.0000
4:74446533:G:GA	acceptor_gain	1.0000
4:74446533:G:GT	acceptor_gain	1.0000
4:74446533:GG:G	acceptor_gain	1.0000
4:74446533:GGC:G	acceptor_gain	1.0000
4:74446533:GGCC:G	acceptor_gain	1.0000
4:74446533:GGCCA:G	acceptor_gain	1.0000
4:74446780:GAG:G	donor_gain	1.0000
4:74446780:GAGGT:G	donor_loss	1.0000
4:74446781:AGG:A	donor_loss	1.0000
4:74446783:G:C	donor_loss	1.0000
4:74446783:G:GG	donor_gain	1.0000
4:74446783:GT:G	donor_loss	1.0000
4:74446784:T:A	donor_loss	1.0000
4:74449045:A:AG	acceptor_gain	1.0000
4:74449046:G:GA	acceptor_gain	1.0000
4:74449046:GTT:G	acceptor_gain	1.0000
4:74450374:TTGCA:T	acceptor_loss	1.0000
4:74450375:TGCA:T	acceptor_loss	1.0000
4:74450376:GCA:G	acceptor_loss	1.0000
4:74450377:CAGA:C	acceptor_loss	1.0000
4:74450378:A:AG	acceptor_gain	1.0000

AlphaMissense

1649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:74449196:T:A	C154S	0.997
4:74449197:G:C	C154S	0.997
4:74450408:T:A	C181S	0.997
4:74450409:G:C	C181S	0.997
4:74449211:T:A	C159S	0.996
4:74449212:G:C	C159S	0.996
4:74449172:T:A	C146S	0.994
4:74449173:G:C	C146S	0.994
4:74449197:G:A	C154Y	0.993
4:74449206:G:T	G157V	0.993
4:74449196:T:C	C154R	0.992
4:74449198:C:G	C154W	0.992
4:74449206:G:A	G157E	0.992
4:74450381:T:A	C172S	0.992
4:74450382:G:C	C172S	0.992
4:74449244:T:A	C170S	0.991
4:74449245:G:C	C170S	0.991
4:74449211:T:C	C159R	0.990
4:74450408:T:C	C181R	0.989
4:74449173:G:A	C146Y	0.988
4:74449196:T:G	C154G	0.988
4:74449245:G:A	C170Y	0.988
4:74449197:G:T	C154F	0.987
4:74450400:G:T	G178V	0.987
4:74450409:G:A	C181Y	0.987
4:74450409:G:T	C181F	0.986
4:74449244:T:C	C170R	0.985
4:74450381:T:C	C172R	0.985
4:74450406:G:C	R180P	0.985
4:74449213:C:G	C159W	0.984

dbSNP variants (sampled 300 via entrez): RS1000042196 (4:74450284 T>A,C), RS1000485195 (4:74445545 C>T), RS1000658719 (4:74449688 G>C), RS1000778599 (4:74447347 G>A), RS1000835953 (4:74445904 T>A), RS1001232134 (4:74447055 C>T), RS1001332648 (4:74446023 G>T), RS1001333937 (4:74452833 C>T), RS1001384107 (4:74452629 A>G), RS1001679242 (4:74446301 A>T), RS1001825458 (4:74444047 C>T), RS1002175059 (4:74446743 C>A,G,T), RS1002944971 (4:74447941 T>C), RS1003002508 (4:74454261 T>C,G), RS1003054563 (4:74453924 A>G)

Disease associations

OMIM: gene MIM:104640 | disease phenotypes: MIM:313200, MIM:300068, MIM:167000, MIM:300633, MIM:307300, MIM:312100, MIM:312300, MIM:301120, MIM:176807, MIM:400044

GenCC curated gene-disease

Disease	Classification	Inheritance
androgen insensitivity syndrome	Definitive	X-linked
Kennedy disease	Definitive	X-linked
partial androgen insensitivity syndrome	Strong	X-linked
complete androgen insensitivity syndrome	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Kennedy disease	Definitive	XL

Mondo (15): Kennedy disease (MONDO:0010735), androgen insensitivity syndrome (MONDO:0019154), ovarian cancer (MONDO:0008170), male infertility (MONDO:0005372), prostate cancer (MONDO:0008315), hypospadias 1, X-linked (MONDO:0010384), partial androgen insensitivity syndrome (MONDO:0010720), prostate cancer, hereditary, X-linked 3 (MONDO:0971170), primary ovarian failure (MONDO:0005387), complete androgen insensitivity syndrome (MONDO:0021023), prostate cancer, hereditary (MONDO:0700275), disorder of sexual differentiation (MONDO:0002145), posterior hypospadias (MONDO:0019848), Castleman-Kojima disease (MONDO:0018702), 46,XY complete gonadal dysgenesis (MONDO:0010765)

Orphanet (13): Kennedy disease (Orphanet:481), Androgen insensitivity syndrome (Orphanet:754), Complete androgen insensitivity syndrome (Orphanet:99429), Rare ovarian cancer (Orphanet:213500), Familial prostate cancer (Orphanet:1331), OBSOLETE: Familial hypospadias (Orphanet:440), Partial androgen insensitivity syndrome (Orphanet:90797), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), Difference of sex development (Orphanet:90771), Non-syndromic posterior hypospadias (Orphanet:95706), TAFRO syndrome (Orphanet:457077), 46,XY complete gonadal dysgenesis (Orphanet:242), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000250_1	Male-pattern baldness	5.000000e-11
GCST000283_7	LDL cholesterol	2.000000e-07
GCST001148_3	Prostate cancer	1.000000e-08
GCST001297_1	Male-pattern baldness	3.000000e-22
GCST001548_8	Male-pattern baldness	2.000000e-91
GCST001585_33	Breast size	5.000000e-08
GCST002667_1	Mammographic density (dense area)	2.000000e-10
GCST002667_2	Mammographic density (dense area)	8.000000e-10
GCST003455_38	Spherical equivalent (joint analysis main effects and education interaction)	6.000000e-10
GCST003480_2	Balding	2.000000e-08
GCST003979_8	Excessive daytime sleepiness	4.000000e-08
GCST003983_1	Male-pattern baldness	1.000000e-247
GCST003985_7	Breast size	9.000000e-13
GCST005116_58	Male-pattern baldness	3.000000e-35
GCST006661_218	Male-pattern baldness	5.000000e-178
GCST006988_20	Blond vs. brown/black hair color	1.000000e-22
GCST90020091_14	Estradiol levels	6.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005941	mammographic density measurement
EFO:0006503	dense area measurement
EFO:0004784	self reported educational attainment
EFO:0007825	balding measurement
EFO:0007875	excessive daytime sleepiness measurement
EFO:0003924	hair color
EFO:0004697	estradiol measurement

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D013734	Androgen-Insensitivity Syndrome	C12.050.351.875.253.096.500; C12.200.706.316.096.500; C12.800.316.096.500; C16.131.939.316.096.500; C16.320.322.061; C19.391.119.096.500
D055534	Bulbo-Spinal Atrophy, X-Linked	C10.228.854.468.399; C10.574.500.175; C10.574.562.500.374; C10.668.467.500.186; C16.320.322.076; C16.320.400.100
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D006061	Gonadal Dysgenesis, 46,XY	C12.050.351.875.253.096.687; C12.050.351.875.253.309.388; C12.200.706.316.096.687; C12.200.706.316.309.388; C12.800.316.096.687; C12.800.316.309.388; C16.131.939.316.096.687; C16.131.939.316.309.388; C19.391.119.096.687; C19.391.119.309.388
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C567482	Hypospadias 1, X-Linked (supp.)
C538435	Lubs syndrome (supp.)
C537243	Prostate cancer, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3731 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 5 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
AREG Expression	Panitumumab	Colorectal Cancer	Sensitivity/Response	CIViC B	EID1020
AREG Expression	Cetuximab	Colorectal Cancer	Sensitivity/Response	CIViC B	EID788
AREG Expression	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC B	EID781 +1
AREG Expression	Docetaxel + Cetuximab	Head And Neck Squamous Cell Carcinoma	Resistance	CIViC B	EID846

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11942466	Efficacy	3	cetuximab;irinotecan;panitumumab	Colorectal Neoplasms
rs11942466	Efficacy	3	capecitabine;radiotherapy	Rectal Neoplasms
rs13104811	Efficacy	3	cetuximab;irinotecan;panitumumab	Colorectal Neoplasms
rs1353295	Efficacy	3	cetuximab;irinotecan;panitumumab	Colorectal Neoplasms
rs9996584	Efficacy	3	cetuximab;irinotecan;panitumumab	Colorectal Neoplasms

PharmGKB variants

10 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1353295	AREG	3	1.75	1	cetuximab;irinotecan;panitumumab
rs1615111	AREG		0.00	0
rs2132065	AREG		0.00	0
rs3913032	AREG		0.00	0
rs6447003	AREG		0.00	0
rs9996584	AREG	3	4.50	1	cetuximab;irinotecan;panitumumab
rs10034692	AREG		0.00	0
rs11725706	AREG		0.00	0
rs11942466	AREG	3	5.50	2	capecitabine;radiotherapy;cetuximab;irinotecan;panitumumab
rs13104811	AREG	3	2.25	1	cetuximab;irinotecan;panitumumab

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.46	IC50	350	nM	CHEMBL62259
6.33	IC50	470	nM	CHEMBL154706
6.02	IC50	950	nM	CHEMBL347440
6.01	IC50	970	nM	CHEMBL406939
5.83	IC50	1470	nM	CHEMBL435462

PubChem BioAssay actives

5 with measured affinity, of 5 total; 5 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
(3R)-2-[ethoxy-(4-methoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	220635: In vitro amphiregulin shedding inhibition	ic50	0.3500	uM
(3R)-2-[2-fluoroethoxy-(4-methoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	220635: In vitro amphiregulin shedding inhibition	ic50	0.4700	uM
(3R)-N-hydroxy-2-[(4-methoxyphenyl)-(2,2,2-trifluoroethoxy)phosphoryl]-3,4-dihydro-1H-isoquinoline-3-carboxamide	220635: In vitro amphiregulin shedding inhibition	ic50	0.9500	uM
(3R)-N-hydroxy-2-[(4-methoxyphenyl)-(3,3,3-trifluoropropoxy)phosphoryl]-3,4-dihydro-1H-isoquinoline-3-carboxamide	220635: In vitro amphiregulin shedding inhibition	ic50	0.9700	uM
(3R)-2-[2,2-difluoroethoxy-(4-methoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	220635: In vitro amphiregulin shedding inhibition	ic50	1.4700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases phosphorylation, affects expression, increases reaction, decreases reaction (+1 more)	21
Benzo(a)pyrene	affects methylation, increases expression	8
Particulate Matter	increases abundance, increases expression, increases secretion, decreases expression, decreases reaction	7
Fulvestrant	decreases reaction, increases expression, decreases expression	6
Tetrachlorodibenzodioxin	increases expression, increases secretion, affects reaction, increases activity, affects expression (+2 more)	6
bisphenol A	affects expression, increases expression, affects cotreatment, decreases expression	5
Gefitinib	affects cotreatment, increases phosphorylation, affects response to substance, decreases response to substance, decreases reaction (+1 more)	5
Air Pollutants	increases expression, increases abundance, increases secretion, decreases expression	4
Colforsin	increases expression, decreases reaction	4
Methotrexate	affects cotreatment, increases expression, decreases expression	4
Smoke	decreases expression, decreases nitrosation, increases abundance	4
Tobacco Smoke Pollution	decreases expression, increases expression	4
sodium arsenite	decreases expression, increases expression	3
Cadmium	decreases expression, increases abundance, increases expression, decreases reaction	3
Calcitriol	increases expression, decreases reaction	3
Tamoxifen	affects cotreatment, increases expression, decreases reaction	3
Valproic Acid	increases reaction, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	3
Genistein	increases expression	3
Raloxifene Hydrochloride	affects cotreatment, increases expression, decreases expression	3
afimoxifene	decreases expression, increases expression	2
nickel sulfate	decreases expression, increases expression	2
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases reaction, increases expression	2
batimastat	decreases reaction, increases cleavage, increases secretion, decreases secretion	2
U 0126	decreases reaction, increases expression, decreases secretion	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Decitabine	increases expression	2
Acetaminophen	decreases expression	2
Cannabidiol	increases expression	2
Chlorpromazine	decreases expression	2

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL824094	Functional	In vitro amphiregulin shedding inhibition	New strategy for antedrug application: development of metalloproteinase inhibitors as antipsoriatic drugs. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8BF	Abcam HCT 116 AREG KO	Cancer cell line	Male
CVCL_B9DI	Abcam A-549 AREG KO	Cancer cell line	Male
CVCL_D2DW	Abcam MCF-7 AREG KO	Cancer cell line	Female
CVCL_D7KB	Ubigene A-549 AREG KO	Cancer cell line	Male
CVCL_D8HG	Ubigene HCT 116 AREG KO	Cancer cell line	Male
CVCL_D9XS	Ubigene HeLa AREG KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00851461	PHASE4	COMPLETED	Effect of Goserelin (Zoladex®) in Spinal and Bulbar Muscular Atrophy
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
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