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 c... See more...

Aliases for AREG Gene

Aliases for AREG Gene

  • Amphiregulin 2 3 4 5
  • Colorectum Cell-Derived Growth Factor 3 4
  • Schwannoma-Derived Growth Factor 2 3
  • Amphiregulin B 2 3
  • AREGB 3 4
  • CRDGF 3 4
  • SDGF 3 4
  • AR 3 4

External Ids for AREG Gene

Previous HGNC Symbols for AREG Gene

  • SDGF
  • AREGB

Previous GeneCards Identifiers for AREG Gene

  • GC04P075300
  • GC04P075550
  • GC04P075711
  • GC04P075777
  • GC04P075675
  • GC04P071121

Summaries for AREG Gene

Entrez Gene Summary for AREG Gene

  • 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. [provided by RefSeq, Apr 2014]

CIViC Summary for AREG Gene

GeneCards Summary for AREG Gene

AREG (Amphiregulin) is a Protein Coding gene. Diseases associated with AREG include Ovarian Cystadenoma and Colorectal Cancer. Among its related pathways are Metabolism of proteins and ERK Signaling. Gene Ontology (GO) annotations related to this gene include cytokine activity and epidermal growth factor receptor binding. An important paralog of this gene is HBEGF.

UniProtKB/Swiss-Prot Summary for AREG Gene

  • 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.

Gene Wiki entry for AREG Gene

Additional gene information for AREG Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AREG Gene

Genomics for AREG Gene

GeneHancer (GH) Regulatory Elements for AREG Gene

Promoters and enhancers for AREG Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J074444 Promoter/Enhancer 0.8 EPDnew Ensembl dbSUPER 500.7 +1.9 1903 4.8 AREG piR-40176-021
GH04J074092 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 12.5 -348.2 -348208 8.6 CTCF TCF12 GTF2E2 PHF8 ZIC2 POLR2A ZBTB10 ZBTB11 TCF7 TAF7 CXCL2 CXCL3 ANKRD17 ENSG00000250220 CXCL8 EREG MTHFD2L AREG HMGA1P2 lnc-CXCL3-3
GH04J074617 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 6.4 +180.8 180803 16.6 EP300 CTCF TCF12 POLR2G JUND FOS REST RFX1 RUNX1 RAD21 EPGN EREG AREG piR-46381-057 piR-48369-134
GH04J074363 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 5.5 -78.5 -78475 5.8 EP300 TCF12 ZBTB5 POLR2A ZNF263 ZBTB26 CTBP1 EZH2 KDM5B KDM1A EREG PARM1-AS1 EPGN AREG piR-33422-319
GH04J074407 Enhancer 1.1 FANTOM5 Ensembl ENCODE dbSUPER 7 -34.8 -34834 6.5 CREB1 ZNF316 FOS FOSL1 ZNF513 MAFK STAT3 MAFG BHLHE40 BCL3 HSALNG0035212 AREG CXCL2 piR-31470-368
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AREG on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for AREG

Top Transcription factor binding sites by QIAGEN in the AREG gene promoter:
  • AML1a
  • AP-1
  • ATF-2
  • c-Jun
  • C/EBPalpha
  • POU2F1a
  • STAT3

Genomic Locations for AREG Gene

Genomic Locations for AREG Gene
chr4:74,445,098-74,455,009
(GRCh38/hg38)
Size:
9,912 bases
Orientation:
Plus strand
chr4:75,310,851-75,320,726
(GRCh37/hg19)
Size:
9,876 bases
Orientation:
Plus strand

Genomic View for AREG Gene

Genes around AREG on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AREG Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AREG Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AREG Gene

Proteins for AREG Gene

  • Protein details for AREG Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P15514-AREG_HUMAN
    Recommended name:
    Amphiregulin
    Protein Accession:
    P15514
    Secondary Accessions:
    • Q5U026

    Protein attributes for AREG Gene

    Size:
    252 amino acids
    Molecular mass:
    27895 Da
    Quaternary structure:
    • The immature precursor interacts with CNIH.
    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.

    Three dimensional structures from OCA and Proteopedia for AREG Gene

neXtProt entry for AREG Gene

Post-translational modifications for AREG Gene

  • Glycosylation at Asn30, Ser41, Thr52, Ser53, Asn113, Asn119, and Thr169
  • Modification sites at PhosphoSitePlus

Other Protein References for AREG Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Boster Bio Antibodies for AREG

No data available for DME Specific Peptides for AREG Gene

Domains & Families for AREG Gene

Gene Families for AREG Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted membrane proteins

Protein Domains for AREG Gene

Blocks:
  • Type I EGF
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for AREG Gene

GenScript: Design optimal peptide antigens:
  • Colorectum cell-derived growth factor (AREG_HUMAN)
  • Amphiregulin (Schwannoma-derived growth factor) (Q5U026_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P15514

UniProtKB/Swiss-Prot:

AREG_HUMAN :
  • Belongs to the amphiregulin family.
Family:
  • Belongs to the amphiregulin family.
genes like me logo Genes that share domains with AREG: view

Function for AREG Gene

Molecular function for AREG Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
By phorbol 12-myristate 13-acetate (PMA).
GENATLAS Biochemistry:
amphiregulin,27.9kDa,bifunctional protein possessing an epithelial cell growth regulator (EGF family) and a tumor-inhibitory activity

Phenotypes From GWAS Catalog for AREG Gene

Gene Ontology (GO) - Molecular Function for AREG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IEA --
GO:0005154 epidermal growth factor receptor binding IEA,IBA 21873635
GO:0005515 protein binding IPI 19740107
GO:0008083 growth factor activity IBA,TAS 21873635
genes like me logo Genes that share ontologies with AREG: view
genes like me logo Genes that share phenotypes with AREG: view

Animal Models for AREG Gene

MGI Knock Outs for AREG:
  • Areg Areg<tm1Dle>
  • Areg Areg<tm2b(EUCOMM)Hmgu>

miRNA for AREG Gene

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for AREG Gene

Localization for AREG Gene

Subcellular locations from UniProtKB/Swiss-Prot for AREG Gene

Membrane; Single-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AREG gene
Compartment Confidence
extracellular 5
nucleus 4
endoplasmic reticulum 4
golgi apparatus 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endosome 2
cytosol 2
lysosome 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for AREG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA,TAS 12743035
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with AREG: view

Pathways & Interactions for AREG Gene

PathCards logo

SuperPathways for AREG Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
2 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
3 ERK Signaling
.61
.61
.58
.51
.49
4 Transport to the Golgi and subsequent modification
5 Nanog in Mammalian ESC Pluripotency
.61
.61
.59
.48
genes like me logo Genes that share pathways with AREG: view

Pathways by source for AREG Gene

2 GeneGo (Thomson Reuters) pathways for AREG Gene
  • Development EGFR signaling pathway
  • Development ERBB-family signaling
1 R&D Systems pathway for AREG Gene
55 Qiagen pathways for AREG Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR

SIGNOR curated interactions for AREG Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for AREG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0006888 ER to Golgi vesicle-mediated transport TAS --
GO:0007165 signal transduction TAS --
GO:0007173 epidermal growth factor receptor signaling pathway TAS,IEA --
GO:0007186 G protein-coupled receptor signaling pathway IDA 12743035
genes like me logo Genes that share ontologies with AREG: view

Drugs & Compounds for AREG Gene

(32) Drugs for AREG Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cetuximab Approved Pharma EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors 852
Capecitabine Approved, Investigational Pharma RNA processing inhibitor and thymidylate synthase inhibitor, F-pyrimidines 1594
Irinotecan Approved, Investigational Pharma Topoisomerase I inhibitor, TOPO I inhibitor, Topoisomerase 1 Inhibitors 1353
Panitumumab Approved, Investigational Pharma EGFR inhibitor, EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors 234
radiotherapy Pharma 0

(23) Additional Compounds for AREG Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with AREG: view

Transcripts for AREG Gene

mRNA/cDNA for AREG Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for AREG Gene

No ASD Table

Relevant External Links for AREG Gene

GeneLoc Exon Structure for
AREG

Expression for AREG Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for AREG Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for AREG Gene

This gene is overexpressed in Whole Blood (x7.0).

Protein differential expression in normal tissues from HIPED for AREG Gene

This gene is overexpressed in Liver (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AREG Gene



Protein tissue co-expression partners for AREG Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for AREG

SOURCE GeneReport for Unigene cluster for AREG Gene:

Hs.270833

Evidence on tissue expression from TISSUES for AREG Gene

  • Nervous system(4.3)
  • Lung(3.1)
  • Skin(2.6)
  • Intestine(2.5)
  • Stomach(2.1)
genes like me logo Genes that share expression patterns with AREG: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for AREG Gene

Orthologs for AREG Gene

This gene was present in the common ancestor of chordates.

Orthologs for AREG Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia AREG 31 30
  • 99.07 (n)
OneToMany
dog
(Canis familiaris)
Mammalia LOC475176 30
  • 86.75 (n)
-- 31
  • 83 (a)
OneToMany
cow
(Bos Taurus)
Mammalia LOC538751 30
  • 85.77 (n)
-- 31
  • 78 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Areg 17 31 30
  • 78.1 (n)
rat
(Rattus norvegicus)
Mammalia Areg 30
  • 76.19 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 53 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 52 (a)
OneToMany
chicken
(Gallus gallus)
Aves AREGB 30
  • 59.15 (n)
AREG 31
  • 45 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 39 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100145251 30
  • 54.9 (n)
zebrafish
(Danio rerio)
Actinopterygii AREG 31
  • 22 (a)
OneToMany
Species where no ortholog for AREG was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for AREG Gene

ENSEMBL:
Gene Tree for AREG (if available)
TreeFam:
Gene Tree for AREG (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AREG: view image

Paralogs for AREG Gene

Paralogs for AREG Gene

(2) SIMAP similar genes for AREG Gene using alignment to 2 proteins:

  • AREG_HUMAN
  • D6RFX5_HUMAN
genes like me logo Genes that share paralogs with AREG: view

Variants for AREG Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for AREG Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
790830 Benign: not provided 74,446,570(+) A/G MISSENSE_VARIANT
rs28364979 - p.Tyr81Cys
rs373527160 - p.Asp80Val

Additional dbSNP identifiers (rs#s) for AREG Gene

Structural Variations from Database of Genomic Variants (DGV) for AREG Gene

Variant ID Type Subtype PubMed ID
dgv2829n106 CNV deletion 24896259
esv2664200 CNV deletion 23128226
nsv1009099 CNV gain 25217958
nsv1074187 CNV deletion 25765185
nsv525980 CNV gain 19592680
nsv950052 CNV deletion 24416366

Variation tolerance for AREG Gene

Gene Damage Index Score: 2.15; 38.98% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AREG Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
AREG

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AREG Gene

Disorders for AREG Gene

MalaCards: The human disease database

(27) MalaCards diseases for AREG Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
ovarian cystadenoma
  • cystoma serosum simplex
colorectal cancer
  • crc
psoriasis
breast cancer
  • breast cancer, familial
squamous blepharitis
- elite association - COSMIC cancer census association via MalaCards
Search AREG in MalaCards View complete list of genes associated with diseases

Additional Disease Information for AREG

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Tumor Gene Database
(TGDB)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with AREG: view

No data available for UniProtKB/Swiss-Prot and Genatlas for AREG Gene

Publications for AREG Gene

  1. Colorectum cell-derived growth factor (CRDGF) is homologous to amphiregulin, a member of the epidermal growth factor family. (PMID: 1333777) Culouscou JM … Shoyab M (Growth factors (Chur, Switzerland) 1992) 3 4 23 54
  2. A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin. (PMID: 2017164) Cook PW … Shipley GD (Molecular and cellular biology 1991) 3 4 23 54
  3. Clarification of the C-terminal proteolytic processing site of human Amphiregulin. (PMID: 22967896) Levano KS … Kenny PA (FEBS letters 2012) 3 4 54
  4. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot". (PMID: 20628624) Johnatty SE … Australian Cancer Study (Ovarian Cancer) (PLoS genetics 2010) 3 41 54
  5. BRCA1 represses amphiregulin gene expression. (PMID: 20103632) Lamber EP … Parvin JD (Cancer research 2010) 3 23 54

Products for AREG Gene

Sources for AREG Gene