GPER1

Chr 7

G protein-coupled estrogen receptor 1

Also known as: CEPR, CMKRL2, DRY12, FEG-1, GPCR-Br, GPER, GPR30, LERGU

NCBI Gene: 2852ENSG00000164850UniProt: Q99527

This gene encodes a multi-pass membrane protein that localizes to the endoplasmic reticulum and a member of the G-protein coupled receptor 1 family. This receptor binds estrogen and activates multiple downstream signaling pathways, leading to stimulation of adenylate cyclase and an increase in cyclic AMP levels, while also promoting intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. This receptor has been shown to play a role in diverse biological processes, including bone and nervous system development, metabolism, cognition, male fertility and uterine function. [provided by RefSeq, Aug 2017]

123
ClinVar variants
39
Pathogenic / LP
0.57
pLI score
0
Active trials
Clinical Summary— GPER1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 77 VUS of 123 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.69LOEUF
pLI 0.574
Z-score 2.07
OE 0.15 (0.05–0.69)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.11Z-score
OE missense 0.81 (0.72–0.91)
218 obs / 269.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.05–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.72–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 1 / 6.8Missense obs/exp: 218 / 269.2Syn Z: -0.20

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic1
VUS77
Likely Benign5
Benign2
38
Pathogenic
1
Likely Pathogenic
77
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
1
0
1
VUS
0
59
18
0
77
Likely Benign
0
2
2
1
5
Benign
0
2
0
0
2
Total063591123

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GPER1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Role of estrogen receptors in health and disease.
Chen P et al.·Front Endocrinol (Lausanne)
2022Review
G Protein-Coupled Estrogen Receptor, GPER1, Offers a Novel Target for the Treatment of Digestive Diseases.
DeLeon C et al.·Front Endocrinol (Lausanne)
2020Review
GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells.
Bühler M et al.·Life Sci Alliance
2022
GPER1/ACACB are potential target genes associated with intracranial aneurysm and vascular endothelial cell senescence.
Zeng L et al.·Neurosurg Rev
2025
Oestrogen receptor-independent actions of oestrogen in cancer.
Gopinath P et al.·Mol Biol Rep
2023Review
The role of estrogen receptors in lung diseases.
Ekpruke CD et al.·Am J Physiol Lung Cell Mol Physiol
2026Review
Selective Activation of G Protein-coupled Estrogen Receptor 1 Attenuates Atherosclerosis.
Haider MZ et al.·Curr Med Chem
2024Review
Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse.
Hara Y et al.·Physiol Rev
2015Review
G-Protein-coupled Estrogen Receptor 1 (GPER1) Overexpression Affects Aggressiveness of Cervical Carcinoma Cells Depending on Histological Entity.
Hambach L et al.·Cancer Genomics Proteomics
2025
Estrogen Receptor Genes, Cognitive Decline, and Alzheimer Disease.
Oveisgharan S et al.·Neurology
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools