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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GDF9
growth differentiation factor 9
Chromosome 5 Β· 5q31.1
NCBI Gene: 2661Ensembl: ENSG00000164404.9HGNC: HGNC:4224UniProt: B4DXG3
111PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of progesterone secretionpositive regulation of cell population proliferationcytokine activitycell surface receptor protein serine/threonine kinase signaling pathway46,XX gonadal dysgenesisgenetic non-acquired premature ovarian failureprimary ovarian insufficiencyIsolated CoQ-cytochrome C reductase deficiency
✦AI Summary

GDF9 (growth differentiation factor 9) is a critical oocyte-secreted growth factor that regulates ovarian folliculogenesis and female fertility 1. The protein belongs to the TGF-Ξ² superfamily and plays essential roles in controlling follicular development through paracrine signaling between oocytes and surrounding granulosa cells 2. GDF9 promotes granulosa cell proliferation and differentiation, regulates follicular survival, and supports oocyte maturation 2. Together with BMP15, GDF9 modulates cumulus cell expansion, which is critical for normal ovulation 34. The factor also influences steroid hormone synthesis and creates an optimal follicular environment supporting oocyte developmental competence 1. Mutations in GDF9 are associated with primary ovarian insufficiency (POI), a condition characterized by premature ovarian failure before age 40 56. Additionally, GDF9 variants are significantly more frequent in mothers of dizygotic twins, suggesting a role in hyperovulation 7. Dysregulation of GDF9 expression has been implicated in polycystic ovary syndrome, where altered oocyte maturation genes including GDF9 contribute to follicular arrest and ovulation dysfunction 8. These findings establish GDF9 as a master regulator of ovarian function with significant clinical implications for reproductive health.

Sources cited
1
GDF9 is an oocyte-secreted factor with leading role in ovarian function control, modulating granulosa cells and oocyte quality
PMID: 29544636
2
GDF9 belongs to TGF-Ξ² superfamily, contributes to follicular development through paracrine signaling, and regulates proliferation/differentiation and oocyte maturation
PMID: 31607184
3
GDF9 plays a leading role in cumulus cell expansion process critical for normal fertility
PMID: 15917343
4
GDF9 works with BMP15 to control cumulus cell differentiation and participates in late maturation process
PMID: 16959524
5
GDF9 is associated with primary ovarian insufficiency as a causative genetic factor
PMID: 26243799
6
GDF9 mutations are linked to nonsyndromic POI and implicated in ovarian development pathways
PMID: 34794894
7
GDF9 mutations are significantly more frequent in mothers of dizygotic twins
PMID: 18024802
8
GDF9 expression is decreased in follicles with androgen excess, contributing to ovarian dysfunction in PCOS
PMID: 35237237
Disease Associationsβ“˜21
46,XX gonadal dysgenesisOpen Targets
0.73Strong
genetic non-acquired premature ovarian failureOpen Targets
0.33Weak
primary ovarian insufficiencyOpen Targets
0.22Weak
Isolated CoQ-cytochrome C reductase deficiencyOpen Targets
0.15Weak
mitochondrial complex III deficiency nuclear type 1Open Targets
0.12Weak
polycystic ovary syndromeOpen Targets
0.12Weak
Testicular regression syndromeOpen Targets
0.07Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.07Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.06Suggestive
endometriosisOpen Targets
0.06Suggestive
ovarian dysgenesis 10Open Targets
0.06Suggestive
ovarian dysgenesis 9Open Targets
0.06Suggestive
Familial hyperprolactinemiaOpen Targets
0.06Suggestive
familial hyperprolactinemiaOpen Targets
0.06Suggestive
ovarian dysgenesis 11Open Targets
0.06Suggestive
Hypergonadotropic hypogonadism - cataract syndromeOpen Targets
0.06Suggestive
hypergonadotropic hypogonadism-cataract syndromeOpen Targets
0.06Suggestive
premature ovarian failure 18Open Targets
0.06Suggestive
premature ovarian failure 8Open Targets
0.06Suggestive
46,XY sex reversal 11Open Targets
0.06Suggestive
Premature ovarian failure 14UniProt
Pathogenic Variants6
NM_005260.7(GDF9):c.759_762del (p.Phe254fs)Likely pathogenic
Premature ovarian failure 14
β˜…β˜†β˜†β˜†2024β†’ Residue 254
NM_005260.7(GDF9):c.783del (p.Ser262fs)Likely pathogenic
Premature ovarian failure 14
β˜…β˜†β˜†β˜†2024β†’ Residue 262
NM_005260.7(GDF9):c.1364A>C (p.Ter455Ser)Likely pathogenic
Premature ovarian failure 14
β˜…β˜†β˜†β˜†2021β†’ Residue 455
NM_005260.7(GDF9):c.1121C>T (p.Pro374Leu)Pathogenic
Premature ovarian failure 14
β˜†β˜†β˜†β˜†2024β†’ Residue 374
NM_005260.7(GDF9):c.794T>G (p.Leu265Ter)Pathogenic
Premature ovarian failure 14
β˜†β˜†β˜†β˜†2024β†’ Residue 265
NM_005260.7(GDF9):c.946C>T (p.Arg316Cys)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 316
View on ClinVar β†—
Related Genes
ZP3Protein interaction100%ZP2Protein interaction100%ZP4Protein interaction98%ZAR1Protein interaction97%FSTProtein interaction89%RFPL4AProtein interaction88%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
56%
Brain
49%
Heart
42%
Ovary
35%
Lung
21%
Gene Interaction Network
Click a node to explore
GDF9ZP3ZP2ZP4ZAR1FSTRFPL4A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O60383
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.13LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.80 [0.57–1.13]
RankingsWhere GDF9 stands among ~20K protein-coding genes
  • #4,272of 20,598
    Most Researched111 Β· top quartile
  • #3,339of 5,498
    Most Pathogenic Variants6
  • #11,679of 17,882
    Most Constrained (LOEUF)1.13
Genes detectedGDF9
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics of primary ovarian insufficiency: new developments and opportunities.
PMID: 26243799
Hum Reprod Update Β· 2015
1.00
2
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
0.90
3
Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development.
PMID: 35237237
Front Endocrinol (Lausanne) Β· 2022
0.80
4
Molecular Aspects and Clinical Relevance of GDF9 and BMP15 in Ovarian Function.
PMID: 29544636
Vitam Horm Β· 2018
0.70
5
Dizygotic twinning.
PMID: 18024802
Hum Reprod Update Β· 2008
0.60