Rare variants in GPR3 in POI patients: a case series with review of literature
Related Experiment Video
Updated: Jul 11, 2025
Fertility Preservation in Patients with Severe Ovarian Dysfunction
Published on: March 25, 2021
Shuting Ren1, Feng Zhang1,2, Lingyue Shang1
1Obstetrics and Gynecology Hospital, NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), State Key Laboratory of Genetic, Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China.
Background:
Premature ovarian insufficiency (POI) is a highly heterogeneous disease, and up to 25% of the cases can be explained by genetic causes. G protein-coupled receptor 3 (GPR3) plays an important role in oocyte arrest, and Gpr3-deficient mice exhibited POI-like phenotypes.
Case Presentation:
We identified two heterozygous missense variants of GPR3: NM_005281: c.C973T (p.R325C) and c.G772A (p.A258T) in two sporadic Han Chinese POI cases through whole exome sequencing and genetic analysis. The two patients were diagnosed as POI in their late 20s, presenting elevated serum levels of follicle stimulating hormone and secondary amenorrhea. Both variants are very rare in the population databases of ExAC, gnomAD and PGG.Han. The affected amino acids are conserved across species and the mutated amino acids are predicted deleterious with bioinformatics prediction tools and the protein three-dimensional structure analysis.
Conclusions:
It is the first report of rare GPR3 variants associated with POI women, providing an important piece of evidence for GPR3 as a candidate gene which should be screened in POI. This finding suggested the necessity of including GPR3 in etiology study and genetic counseling of POI patients.
Insights
Rare variants in the G protein-coupled receptor 3 (GPR3) gene were identified in women with premature ovarian insufficiency (POI). This finding highlights GPR3 as a potential genetic cause for POI and a target for screening.
Area of Science:
- Genetics
- Reproductive Biology
- Endocrinology
Background:
- Premature ovarian insufficiency (POI) is a complex condition with up to 25% of cases having a genetic basis.
- G protein-coupled receptor 3 (GPR3) is implicated in oocyte arrest, and its deficiency in mice leads to POI-like symptoms.
Conclusions:
- This is the first report linking rare GPR3 variants to premature ovarian insufficiency (POI) in women.
- GPR3 is proposed as a candidate gene for POI, warranting screening in affected individuals.
- The findings emphasize the importance of including GPR3 in the etiological studies and genetic counseling for POI patients.
