GDF9 (Growth Differentiation Factor 9)
Key regulator of ovarian folliculogenesis and female fertility
Gene Information Card
| Symbol | GDF9 |
|---|---|
| Full Name | Growth Differentiation Factor 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | 2661 ncbi.nlm.nih.gov/gene/2661 |
| Ensembl ID | ENSG00000164404 |
| UniProt ID | Q9UK05 |
| OMIM ID | 601918 |
| HGNC ID | 4224 |
| Aliases | GDF-9, MGC138118 |
Description
GDF9 (Growth Differentiation Factor 9) is a member of the transforming growth factor-beta (TGF-beta) superfamily. It is expressed predominantly in oocytes and plays an essential role in ovarian folliculogenesis, including granulosa cell proliferation, cumulus expansion, and oocyte maturation. GDF9 is critical for female fertility; mutations and polymorphisms are associated with premature ovarian failure (POF) and dizygotic twinning.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Premature Ovarian Failure 6 (POF6) | Loss-of-function mutations in GDF9 disrupt oocyte-granulosa cell signaling, leading to follicular atresia and early menopause. | OMIM #618468; ClinVar pathogenic variants |
| Non-obstructive Azoospermia (male infertility) | Rare GDF9 variants may impair spermatogenesis via altered TGF-beta signaling. | PMID: 25657166 |
| Dizygotic Twinning | Certain GDF9 polymorphisms (e.g., rs254286) are associated with increased likelihood of dizygotic twinning. | PMID: 16990545 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Ovary | 12.5 | High |
| Testis | 1.2 | Low |
| Pituitary | 0.8 | Low |
| Uterus | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Oocyte (primary) | 15.0 | Highest expression in germinal vesicle stage |
| Granulosa cells | 0.3 | Low; paracrine action from oocyte |
| KGN (granulosa tumor) | 0.1 | Minimal |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.392C>T (p.Ser131Phe) | Missense | Rare | Loss of function; associated with POF6 |
| c.646G>A (p.Gly216Arg) | Missense | 0.01% | Dominant-negative effect on TGF-beta signaling |
| c.103A>G (p.Thr35Ala) | Missense | 0.5% | Polymorphism linked to twinning |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., Ser131Phe) impair protein secretion or receptor binding, reducing downstream SMAD2/3 signaling.
Gain of Function (GOF)
Not reported for GDF9.
Dominant Negative (DN)
Gly216Arg variant forms non-functional dimers that inhibit wild-type GDF9 activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-beta signaling pathway (KEGG hsa04350)
• Oocyte meiosis (KEGG hsa04114)
• Signaling by TGF-beta family members (Reactome R-HSA-9006936)
Protein Summary
GDF9 is a secreted growth factor synthesized as a preproprotein. After proteolytic cleavage, the mature C-terminal domain forms homodimers that bind to BMPR2 and ACVR1B (ALK4) receptors, activating SMAD2/3 signaling. It is essential for follicular development beyond the primary stage, cumulus cell expansion, and oocyte meiotic competence.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GDF9 Knockout HEK293 Cell Line | EDJ-KQ4695 | Human | 2661 | Details Get a Quote |
| GDF9 Knockout HeLa Cell Line | EDJ-KQ53325 | Human | 2661 | Details Get a Quote |
| GDF9 Knockout A-549 Cell Line | EDJ-KQ61808 | Human | 2661 | Details Get a Quote |
| GDF9 Knockout HCT 116 Cell Line | EDJ-KQ70294 | Human | 2661 | Details Get a Quote |
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