GPER1: G Protein-Coupled Estrogen Receptor 1
A non-classical estrogen receptor involved in rapid signaling, cancer, and metabolic regulation.
Gene Information Card
| Symbol | GPER1 |
|---|---|
| Full Name | G protein-coupled estrogen receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p22.3 |
| NCBI Gene ID | 2852 ncbi.nlm.nih.gov/gene/2852 |
| Ensembl ID | ENSG00000164850 |
| UniProt ID | Q99527 |
| OMIM ID | 601805 |
| HGNC ID | 4489 |
| Aliases | GPR30, CEPR, CMKRL2, DRY12, FEG-1, GPCR-Br, LERGU, LyGPR |
Description
GPER1 (G protein-coupled estrogen receptor 1) encodes a member of the G protein-coupled receptor family. This receptor binds estrogen and mediates rapid non-genomic signaling, distinct from classical nuclear estrogen receptors (ERα/ERβ). It is involved in cell proliferation, migration, and metabolic regulation. GPER1 is expressed in various tissues including breast, ovary, endometrium, and cardiovascular system. Its dysregulation is implicated in cancers (breast, endometrial, ovarian), endometriosis, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | GPER1 activation promotes proliferation and migration via EGFR transactivation and MAPK/ERK signaling. | PMID: 20048001; COSMIC mutations observed in breast tumors. |
| Endometrial cancer | Overexpression of GPER1 correlates with tumor grade and poor prognosis; estrogen-induced signaling via GPER1 enhances cell growth. | PMID: 23327985; ClinVar pathogenic variants reported. |
| Endometriosis | GPER1 expression is elevated in ectopic endometrium; estrogen signaling through GPER1 contributes to lesion growth and inflammation. | PMID: 23536701; OMIM 601805 associated. |
| Ovarian cancer | GPER1 activation stimulates cell invasion and metastasis; high expression linked to worse survival. | PMID: 23269797; COSMIC somatic mutations identified. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 12.5 | Medium |
| Ovary | 8.3 | Low |
| Endometrium | 15.2 | Medium |
| Heart | 6.1 | Low |
| Liver | 3.4 | Not detected |
| Kidney | 7.8 | Low |
| Lung | 5.2 | Low |
| Brain | 9.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF-7 (breast cancer) | 18.4 | High expression; used in functional studies |
| SK-BR-3 (breast cancer) | 22.1 | High expression; HER2-positive line |
| HeLa (cervical cancer) | 11.2 | Moderate expression |
| HUVEC (endothelial) | 7.5 | Low expression |
| K562 (leukemia) | 2.3 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.215C>T (p.Pro72Leu) | Missense | 0.01% (gnomAD) | Unknown; predicted benign |
| c.832G>A (p.Gly278Arg) | Missense | 0.005% (gnomAD) | Unknown; predicted damaging by SIFT |
| c.1003C>T (p.Arg335Trp) | Missense | 0.002% (gnomAD) | Unknown; ClinVar uncertain significance |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in GPER1; start codon loss (p.Met1?) is predicted to cause loss of function.
Gain of Function (GOF)
No confirmed gain-of-function mutations; some variants may alter signaling but not classified.
Dominant Negative (DN)
No dominant-negative mutations described for GPER1.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • estrogen binding (GO:0030284) |
| • G protein-coupled receptor signaling pathway (GO:0007186) | • cell proliferation (GO:0008283) |
| • positive regulation of MAPK cascade (GO:0043410) | • membrane (GO:0016021) |
Pathways
• Estrogen signaling pathway (KEGG hsa04915)
• GPER1-mediated signaling (Reactome R-HSA-9009391)
• EGFR transactivation (PID NCI)
Protein Summary
GPER1 is a 375-amino acid seven-transmembrane G protein-coupled receptor. It localizes to the plasma membrane and endoplasmic reticulum. Upon estrogen binding, it activates G proteins (Gi/o and Gs), leading to downstream signaling including cAMP production, calcium mobilization, and MAPK/ERK activation. GPER1 also transactivates the epidermal growth factor receptor (EGFR) via matrix metalloproteinase-mediated release of heparin-binding EGF. This receptor plays roles in rapid estrogen signaling, cell growth, and metabolism. Its structure includes conserved GPCR motifs and a ligand-binding pocket distinct from classical estrogen receptors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPER1 Knockout HEK293 Cell Line | EDJ-KQ4776 | Human | 2852 | Details Get a Quote |
| GPER1 Knockout HCT 116 Cell Line | EDJ-KQ26311 | Human | 2852 | Details Get a Quote |
| GPER1 Knockout HeLa Cell Line | EDJ-KQ53404 | Human | 2852 | Details Get a Quote |
| GPER1 Knockout A-549 Cell Line | EDJ-KQ61881 | Human | 2852 | Details Get a Quote |
| GPER1 Knockout AsPC-1 Cell Line | EDC07694 | Human | 2852 | Details Get a Quote |
| GPER1（p.R253A and p.R254A） Point Mutation in A-549 Cell Line | EDC03195 | Human | 2852 | Details Get a Quote |
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