EREG (Epiregulin) Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the EREG gene, its protein product, expression patterns, associated diseases, and mutations.
Gene Information Card
| Symbol | EREG |
|---|---|
| Full Name | Epiregulin |
| Gene Type | Protein coding |
| Chromosomal Location | 4q13.3 |
| NCBI Gene ID | 2069 ncbi.nlm.nih.gov/gene/2069 |
| Ensembl ID | ENSG00000124882 |
| UniProt ID | O14944 |
| OMIM ID | 602061 |
| HGNC ID | 3443 |
| Aliases | EPR, ER |
Description
EREG (epiregulin) is a member of the epidermal growth factor (EGF) family of growth factors. It is synthesized as a type I transmembrane protein precursor that is cleaved to release a soluble mature peptide. Epiregulin binds to the epidermal growth factor receptor (EGFR/ERBB1) and ERBB4, and can also activate ERBB2/ERBB3 heterodimers, leading to cell proliferation, differentiation, and survival. It plays roles in normal physiology, including wound healing and tissue repair, and is implicated in various cancers and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Overexpression of EREG activates EGFR signaling, promoting tumor growth and metastasis. | High expression correlates with poor prognosis; therapeutic target for anti-EGFR therapies. |
| Head and neck squamous cell carcinoma | EREG upregulation contributes to EGFR-driven tumor progression. | Elevated EREG expression in tumors; associated with resistance to EGFR inhibitors. |
| Lung cancer | EREG promotes tumor cell proliferation via autocrine/paracrine EGFR activation. | Expression detected in non-small cell lung cancer; potential biomarker. |
| Psoriasis | EREG is overexpressed in psoriatic skin, contributing to epidermal hyperproliferation. | Increased mRNA and protein levels in lesional skin. |
| Ovarian cancer | EREG stimulates cancer cell growth and invasion through EGFR signaling. | High expression in ovarian tumors; associated with aggressive disease. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 12.3 | Medium |
| Skin | 8.9 | Medium |
| Lung | 5.2 | Low |
| Liver | 3.1 | Low |
| Kidney | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 15.2 | High expression |
| MCF7 (Breast carcinoma) | 8.7 | Moderate expression |
| HeLa (Cervical carcinoma) | 6.3 | Low expression |
| HepG2 (Hepatocellular carcinoma) | 2.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.499G>A (p.Gly167Arg) | Missense | Rare (0.01%) | Potential impact on protein function; not well characterized |
| c.1-?_*?del (whole gene deletion) | Deletion | Very rare | Loss of function; may affect development |
| c.602C>T (p.Pro201Leu) | Missense | Not reported in large cohorts | Unknown effect; likely benign |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in EREG are rare and may impair EGFR signaling, potentially affecting development or tissue repair. No specific pathogenic loss-of-function variants are documented in ClinVar.
Gain of Function (GOF)
Gain-of-function mutations are not well-defined; however, overexpression (not mutation) is the primary mechanism in cancer.
Dominant Negative (DN)
No dominant-negative mutations have been reported for EREG.
View complete mutation data：
Gene Ontology (GO)
| • growth factor activity | • epidermal growth factor receptor binding |
| • protein binding | • cell surface receptor signaling pathway |
| • positive regulation of cell proliferation | • positive regulation of MAPK cascade |
| • wound healing |
Pathways
• EGFR tyrosine kinase inhibitor resistance
• ErbB signaling pathway
• MAPK signaling pathway
• PI3K-Akt signaling pathway
• Rap1 signaling pathway
• Ras signaling pathway
Protein Summary
Epiregulin is a 46-amino acid mature peptide (after cleavage) that shares structural homology with EGF. It is synthesized as a 169-amino acid precursor with a transmembrane domain. The mature protein contains six conserved cysteine residues forming three disulfide bonds, characteristic of EGF-like ligands. It binds EGFR and ERBB4 with lower affinity than EGF but can induce potent mitogenic responses. Epiregulin is involved in cell proliferation, differentiation, and survival, and is implicated in tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EREG Knockout HEK293 Cell Line | EDJ-KQ656 | Human | 2069 | Details Get a Quote |
| EREG Knockout A-549 Cell Line | EDJ-KQ18090 | Human | 2069 | Details Get a Quote |
| EREG Knockout HCT 116 Cell Line | EDJ-KQ19163 | Human | 2069 | Details Get a Quote |
| EREG Knockout HeLa Cell Line | EDJ-KQ19164 | Human | 2069 | Details Get a Quote |
| EREG Knockout U-87MG ATCC Cell Line | EDJ-KZ22 | Human | 2069 | Details Get a Quote |
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