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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AREG
amphiregulin
Chromosome 4 · 4q13.3
NCBI Gene: 374Ensembl: ENSG00000109321.12HGNC: HGNC:651UniProt: P15514
234PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
G protein-coupled receptor signaling pathwayGO:0005615positive regulation of cell population proliferationcell surfacecancerneurodegenerative diseasehair colorPrecordial pain
✦AI Summary

AREG (amphiregulin) is an EGFR ligand that functions as an autocrine and paracrine growth factor with diverse roles in immunity, tissue repair, and disease pathology 1. AREG activates EGFR signaling on multiple target cell types, including keratinocytes, hepatic stellate cells, fibroblasts, and immune cells, triggering downstream pathways such as ERK1/2, PI3K/AKT, and Hippo-YAP signaling 234. AREG is produced by diverse cell populations including regulatory T cells, innate lymphoid cells, mast cells, basophils, and cancer-associated fibroblasts 1546. In chr4 liver disease, Treg cell-derived AREG paradoxically promotes liver fibrosis and metabolic dysfunction via hepatic stellate cell EGFR signaling 4. In cancer contexts, AREG contributes to therapeutic resistance and metastatic progression—radiation-induced AREG reprograms myeloid cells toward immunosuppression 7, while fibroblast-derived AREG maintains cancer stem cell stemness in gastric cancer 6. Conversely, lung ILC-derived AREG promotes epithelial repair after influenza infection 5. In psoriasis, IL-17A drives AREG expression via YAP activation, promoting keratinocyte proliferation 3. Elevated serum AREG serves as a biomarker for persistent atrial fibrillation 8. These findings reveal AREG as a context-dependent regulator with both protective and pathogenic functions.

Sources cited
1
Radiotherapy induces AREG expression in tumor cells, which reprograms myeloid cells toward immunosuppression and promotes metastasis
PMID: 40369065
2
Treg cell-derived AREG activates pro-fibrotic programs in hepatic stellate cells via EGFR signaling and promotes NASH-dependent glucose intolerance
PMID: 38309273
3
Cancer-associated fibroblast-derived AREG promotes gastric cancer stem cell stemness via ERBB2 axis and contributes to drug resistance
PMID: 39950944
4
AREG is an EGF-like molecule produced by multiple leukocyte populations and plays critical roles in type 2-mediated immunity, inflammation, and tissue tolerance
PMID: 25692699
5
IL-17A promotes keratinocyte proliferation in psoriasis through ACT1-dependent activation of YAP-AREG axis
PMID: 35304250
6
AREG is the most upregulated gene in monocytes and macrophages in atrial fibrillation, with elevated serum levels predicting persistent AF
PMID: 39622943
7
AREG upregulates SPARC expression in granulosa cells via EGFR and activates ERK1/2, JNK, p38 MAPK, and PI3K/AKT signaling pathways
PMID: 36462647
8
Lung ILC-derived amphiregulin restores airway epithelial integrity and tissue homeostasis after influenza virus infection
PMID: 21946417
Disease Associationsⓘ20
cancerOpen Targets
0.48Moderate
neurodegenerative diseaseOpen Targets
0.39Weak
hair colorOpen Targets
0.23Weak
Precordial painOpen Targets
0.22Weak
rheumatic heart diseaseOpen Targets
0.20Weak
breast fibrocystic diseaseOpen Targets
0.19Weak
colorectal adenocarcinomaOpen Targets
0.19Weak
refractive errorOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
jaw diseaseOpen Targets
0.11Weak
breast diseaseOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.10Suggestive
infectionOpen Targets
0.10Suggestive
head and neck squamous cell carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
melanomaOpen Targets
0.09Suggestive
ovarian cancerOpen Targets
0.09Suggestive
rheumatoid arthritisOpen Targets
0.09Suggestive
SepsisOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ERBB4Protein interaction100%EGFRProtein interaction100%ERBB3Protein interaction99%ADAM17Protein interaction97%FGFR4Protein interaction95%ERBB2Protein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
68%
Heart
6%
Ovary
4%
Liver
2%
Brain
1%
Gene Interaction Network
Click a node to explore
AREGERBB4EGFRERBB3ADAM17FGFR4ERBB2
PROTEIN STRUCTURE
Preparing viewer…
PDB2RNL · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.82LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.54 [0.37–0.82]
RankingsWhere AREG stands among ~20K protein-coding genes
  • #1,699of 20,598
    Most Researched234 · top 10%
  • #6,977of 17,882
    Most Constrained (LOEUF)0.82
Genes detectedAREG
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Radiation-induced amphiregulin drives tumour metastasis.
PMID: 40369065
Nature · 2025
1.00
2
Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis.
PMID: 38309273
Immunity · 2024
0.90
3
Dissecting the Spatial and Single-Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer.
PMID: 39950944
Adv Sci (Weinh) · 2025
0.80
4
Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair.
PMID: 25692699
Immunity · 2015
0.70
5
AREG and EREG Are Predictive Biomarkers of Response to EGFR Inhibition in Gastroesophageal Cancer.
PMID: 40637454
Cancer Res · 2025
0.68