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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FSHR
follicle stimulating hormone receptor
Chromosome 2 Β· 2p16.3
NCBI Gene: 2492Ensembl: ENSG00000170820.12HGNC: HGNC:3969UniProt: B4DXB5
349PubMed Papers
22Diseases
7Drugs
34Pathogenic Variants
FUNCTIONAL ROLE
Receptor
RESEARCH IMPACT
Highly Studied
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionpositive regulation of ERK1 and ERK2 cascadecellular response to follicle-stimulating hormone stimulusplasma membrane46,XX gonadal dysgenesisovarian hyperstimulation syndromeinfertilityanovulation
✦AI Summary

FSHR (follicle-stimulating hormone receptor) is a G protein-coupled receptor that binds follicle-stimulating hormone (FSH) and plays crucial roles in reproductive and metabolic processes 123. Upon FSH binding, FSHR primarily activates GΞ±s protein, leading to increased cAMP production and activation of downstream PI3K-AKT and ERK1/ERK2 signaling pathways 2. The receptor undergoes oligomerization and can form heterodimers with other GPCRs, enabling trans-activation and biased signaling 4. In reproductive tissues, FSHR is essential for spermatogenesis in males and folliculogenesis in females, with complete FSHR loss causing follicular development blockade at the primary stage 5. Core fucosylation by FUT8 is critical for FSHR function, as it enhances FSH-FSHR binding and downstream signaling 6. Beyond reproduction, FSHR is expressed in pancreatic Ξ²-cells where FSH regulates glucose-stimulated insulin secretion in a bell-curve manner through cAMP/PKA and calcium pathways 7. Clinically, FSHR polymorphisms are associated with male infertility risk, particularly combined genotypes showing increased susceptibility 89. The FSHR/GPER expression ratio serves as a biomarker distinguishing mature from immature follicles in assisted reproduction 10. Disease associations include ovarian dysgenesis and ovarian hyperstimulation syndrome.

Sources cited
1
FSHR is a G protein-coupled receptor for FSH
PMID: 11847099
2
FSHR activates downstream PI3K-AKT and ERK1/ERK2 signaling pathways through cAMP production
PMID: 24058690
3
FSHR binds follicle-stimulating hormone
PMID: 24692546
4
FSHR is expressed in pancreatic Ξ²-cells and regulates glucose-stimulated insulin secretion through GΞ±s/cAMP/PKA and calcium pathways
PMID: 37914684
5
Complete FSHR loss results in follicular development blockade at primary stage and FSHR is essential for spermatogenesis
PMID: 34884539
6
FSHR undergoes oligomerization, forms heterodimers with other GPCRs, and exhibits trans-activation and biased signaling
PMID: 30619090
7
Core fucosylation by FUT8 enhances FSH-FSHR binding and downstream signaling
PMID: 38280716
8
FSHR polymorphisms are associated with male infertility risk, particularly combined genotypes
PMID: 26125757
9
FSHR Thr307Ala-Asn680Ser polymorphisms show association with male infertility risk
PMID: 29738186
10
FSHR/GPER ratio distinguishes mature from immature follicles in controlled ovarian cycles
PMID: 40663384
Disease Associationsβ“˜22
46,XX gonadal dysgenesisOpen Targets
0.77Strong
ovarian hyperstimulation syndromeOpen Targets
0.73Strong
infertilityOpen Targets
0.61Moderate
anovulationOpen Targets
0.56Moderate
female infertilityOpen Targets
0.56Moderate
primary ovarian insufficiencyOpen Targets
0.55Moderate
hypogonadismOpen Targets
0.53Moderate
genetic non-acquired premature ovarian failureOpen Targets
0.50Moderate
hypogonadotropic hypogonadismOpen Targets
0.48Moderate
male infertilityOpen Targets
0.47Moderate
46 XX gonadal dysgenesisOpen Targets
0.39Weak
alcohol drinkingOpen Targets
0.38Weak
amenorrheaOpen Targets
0.37Weak
polycystic ovary syndromeOpen Targets
0.34Weak
ovarian dysfunctionOpen Targets
0.34Weak
ovarian neoplasmOpen Targets
0.33Weak
OligomenorrheaOpen Targets
0.32Weak
MenorrhagiaOpen Targets
0.32Weak
PolymenorrheaOpen Targets
0.32Weak
chondrocalcinosisOpen Targets
0.31Weak
Ovarian dysgenesis 1UniProt
Ovarian hyperstimulation syndromeUniProt
Pathogenic Variants34
NM_000145.4(FSHR):c.1121T>A (p.Ile374Asn)Likely pathogenic
Dizygotic twins|Hereditary xanthinuria type 1
β˜…β˜†β˜†β˜†2025β†’ Residue 374
NM_000145.4(FSHR):c.940_941del (p.Leu314fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 314
NM_000145.4(FSHR):c.507del (p.Phe170fs)Likely pathogenic
Ovarian dysgenesis 1
β˜…β˜†β˜†β˜†2023β†’ Residue 170
NM_000145.4(FSHR):c.396dup (p.Lys133Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 133
NM_000145.4(FSHR):c.1109G>A (p.Trp370Ter)Likely pathogenic
Ovarian dysgenesis 1;Ovarian hyperstimulation syndrome
β˜…β˜†β˜†β˜†2021β†’ Residue 370
NM_000145.4(FSHR):c.1862C>T (p.Ala621Val)Likely pathogenic
Ovarian dysgenesis 1
β˜…β˜†β˜†β˜†2020β†’ Residue 621
NM_000145.4(FSHR):c.1384G>C (p.Ala462Pro)Likely pathogenic
Ovarian dysgenesis 1
β˜…β˜†β˜†β˜†2020β†’ Residue 462
NM_000145.4(FSHR):c.2T>C (p.Met1Thr)Pathogenic
Amenorrhea
β˜…β˜†β˜†β˜†2017β†’ Residue 1
NM_000145.4(FSHR):c.1336G>A (p.Gly446Ser)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2014β†’ Residue 446
NM_000145.4(FSHR):c.564_565del (p.Ala189fs)Pathogenic
Ovarian dysgenesis 1
β˜…β˜†β˜†β˜†β†’ Residue 189
NM_000145.4(FSHR):c.1255G>C (p.Ala419Pro)Likely pathogenic
Ovarian hyperstimulation syndrome;Dizygotic twins;Ovarian dysgenesis 1
β˜…β˜†β˜†β˜†β†’ Residue 419
NM_000145.4(FSHR):c.445C>T (p.Leu149Phe)Likely pathogenic
Ovarian hyperstimulation syndrome
β˜†β˜†β˜†β˜†2025β†’ Residue 149
NM_000145.4(FSHR):c.566C>T (p.Ala189Val)Pathogenic
Ovarian dysgenesis 1
β˜†β˜†β˜†β˜†2020β†’ Residue 189
NM_000145.4(FSHR):c.1763T>C (p.Ile588Thr)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 588
NM_000145.4(FSHR):c.884C>T (p.Ser295Phe)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 295
NM_000145.4(FSHR):c.1396G>A (p.Glu466Lys)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 466
NM_000145.4(FSHR):c.1679_1685del (p.Asn560fs)Pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 560
NM_000145.4(FSHR):c.349C>T (p.Gln117Ter)Pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 117
NM_000145.4(FSHR):c.683C>T (p.Thr228Ile)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 228
NM_000145.4(FSHR):c.374T>G (p.Leu125Arg)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 125
View on ClinVar β†—
Drug Targets7
CORIFOLLITROPIN ALFAApproved
Follicle stimulating hormone receptor agonist
infertility
FOLLITROPINApproved
Follicle stimulating hormone receptor agonist
primary ovarian insufficiency
FOLLITROPIN ALFAApproved
Follicle stimulating hormone receptor agonist
FOLLITROPIN BETAApproved
Follicle stimulating hormone receptor agonist
FOLLITROPIN DELTAApproved
Follicle stimulating hormone receptor agonist
anovulation
MENOTROPINSApproved
Follicle stimulating hormone receptor agonist
female infertility
UROFOLLITROPINApproved
Follicle stimulating hormone receptor agonist
female infertility
Related Genes
GPHB5Protein interaction100%HSD3B1Protein interaction100%GCGProtein interaction98%CGAProtein interaction98%TSHBProtein interaction98%GNASProtein interaction93%
Tissue Expression6 tissues
Ovary
100%
Heart
82%
Brain
4%
Lung
2%
Bone Marrow
2%
Liver
0%
Gene Interaction Network
Click a node to explore
FSHRGPHB5HSD3B1GCGCGATSHBGNAS
PROTEIN STRUCTURE
Preparing viewer…
PDB4AY9 Β· 2.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.07LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.83 [0.65–1.07]
RankingsWhere FSHR stands among ~20K protein-coding genes
  • #907of 20,598
    Most Researched349 Β· top 5%
  • #209of 1,025
    FDA-Approved Drug Targets7 Β· top quartile
  • #1,687of 5,498
    Most Pathogenic Variants34
  • #10,813of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedFSHR
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.
PMID: 37914684
Nat Commun Β· 2023
1.00
2
The Roles of Luteinizing Hormone, Follicle-Stimulating Hormone and Testosterone in Spermatogenesis and Folliculogenesis Revisited.
PMID: 34884539
Int J Mol Sci Β· 2021
0.90
3
FSHR Trans-Activation and Oligomerization.
PMID: 30619090
Front Endocrinol (Lausanne) Β· 2018
0.80
4
Association between sequence variants in the FSHR gene and reproductive outcomes following IVF in predicted normoresponders.
PMID: 37130623
Reprod Biomed Online Β· 2023
0.76
5
Effects of
PMID: 34659133
Front Endocrinol (Lausanne) Β· 2021
0.72