Property Summary

NCBI Gene PubMed Count 83
PubMed Score 270.16
PubTator Score 139.28

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (1)

Disease log2 FC p
ovarian cancer 1.200 1.9e-07

Protein-protein Interaction (10)

Gene RIF (62)

PMID Text
26254468 results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals.
25954833 GDF9 c.169G>T (D57Y), c.546G>A (rs1049127), and BMP15 rs79377927 (788_789insTCT) were associated with premature ovarian failure in the Chinese Hui population.
25368253 Reduced expression of growth and differentiation factor-9 is associated with aggressive behaviour of clear-cell renal cell carcinoma.
25253739 The arginine residue in the pre-helix loop of GDF9 homodimer may prevent the inhibition from its pro-domain or directly alter receptor binding, but this residue in GDF9 does not significantly affect the heterodimer activity.
25172094 GDF9 and BMP15 expression is reduced in primordial, primary, and secondary follicles in ovarian tissues of PCOS patients.
25139161 Data suggest up-regulation of mRNA for GDF9 and BMP15 (bone morphogenetic protein 15) in cumulus granulosa cells serves as biomarker for oocyte maturation, fertilization, embryo quality, and pregnancy in couples undergoing ICSI for male infertility.
24939957 Eleven unique copy number changes are identified in a total of 11 patients, including a tandem duplication of 475 bp, containing part of the GDF9 gene promoter region.
24840335 These results suggest that COCs cultured with recombinant GDF9 in oocyte maturation medium improve oocyte developmental competence and subsequent developmental competence of cloned embryo in cattle.
24438375 Alterations to hGDF9 synthesis and activity can contribute to the most common ovarian pathologies.
24430093 GDF-9 and GDF-15 levels may influence bone parameters in polycystic ovary syndrome
24413384 Oocyte-derived GDF9 does not alter gap junction intercellular communication activity between human granulosa cells.
23851219 genetic association studies in population of Han women in China: Data suggest that a mutation in precursor region of GDF9 (R146C) is associated with premature ovarian failure (POF); R146C mutation found in 3 women with POF but absent in controls.
23523567 FOXL2 expression is required for GDF-9 stimulation of follistatin transcription.
23382188 findings that GDF9:BMP15 heterodimers are the most bioactive ligands in mice and humans compared with homodimers explain many puzzling genetic and physiological data and have important implications for improving female fertility in mammals
23060562 It was shown that human kidney tumours have a reduced or loss of expression of GDF9. In vitro, GDF9 overexpression suppresses the invasiveness, growth and migration of kidney cancer cells.
23011157 CDC6 and GDF-9 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.
22825968 BMP15 and GDF9 transcript levels increase in mature oocytes from women with polycystic ovary syndrome after ovarian stimulation, and might inhibit the progesterone secretion by follicular cells
22234469 GDF9 may contribute to the variation observed in follicular development, ovulation rate, and fecundity between mammals
22159313 GDF-9 levels are inversely correlated with the growth, adhesion and migration of bladder cancer cells in vitro.
21829661 GDF9 decreases basal and activin A-induced FST and FSTL3 expression, and this explains, in part, its enhancing effects on activin A-induced inhibin beta(B)-subunit mRNA expression and inhibin B production in hGL cells
21669410 The expression of GDF9 and BMP15 in oocytes from patients with polycystic ovary syndrome cannot reach the normal level even after ovarian stimulation.
21632818 In the samples from girls/women, the number of developing follicles was greater with GDF9 or BMP15 alone than with no BMP15 or GDF9.
21496799 Higher mature GDF9 levels in the follicular fluid were significantly correlated with oocyte nuclear maturation and embryo quality.
21226076 Integral role of GDF-9 and BMP-15 in ovarian function.
21116689 GDF-9 signaling via ALK-5, can promote cell invasiveness
21042764 GDF-9 can promote the motile and adhesive capacity of PC-3 prostate cancer cells by up-regulating expression of FAK and paxillin in a Smad dependent manner, suggesting a pro-tumourigenic role for GDF-9 in prostate cancer.
20734064 Observational study of gene-disease association. (HuGE Navigator)
20705511 Mutational analysis of the coding region of GDF9 among 216 Chinese polycystic ovary syndrome patients. Five novel missense mutations were discovered namely c.15C>G, c.118T>G, c.133A>G, c.1025A>T and c.1275C>A.
20660033 GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor.
20547206 Impaired production of BMP15 and GDF9 mature proteins derived from proproteins with mutation in the proregion.
20458753 Cell growth was significantly increased in the GDF9 over-expressing cells compared to the two controls; apoptosis was decreased in the presence of GDF9.
20451184 GDF-9 c.G546A, but not c.G169A or c.C447T, is correlated with the poor ovarian stimulation and in vitro fertilization outcomes in women with diminished ovarian reserve.
20451184 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20427239 The detection of GDF9 and TGFbetaR1 at both at the protein and mRNA levels suggests that GDF9 may have functions in human preantral follicles.
20237496 Observational study of gene-disease association. (HuGE Navigator)
20236105 data demonstrate that polymorphisms in major folliculogenesis genes, GDF9, BMP15, AMH, and AMHR2, are not associated with polycystic ovary syndrome susceptibility.
20236105 Observational study of gene-disease association. (HuGE Navigator)
20067794 Data show that Golgi apparatus casein kinase (G-CK) catalyzes the phosphorylation of rhBMP-15 and rhGDF-9.
19931079 GDF-9 concentration in women with severe endometriosis was lower than in those without
19846738 We report here for the first time autocrine roles for endogenous GDF9 in human granulosa-lutein cells in enhancing activin A-induced beta(B)-subunit mRNA and inhibin B levels
19505950 GDF9 regulates the expression of R-SMAD2/3-responsive reporter genes through ALK4, 5 or 7 in extra-ovarian (adrenocortical and Sertoli) cells with similar potency and signalling pathway to its actions on granulosa cells
19438907 2 synonymous mutations (c.447C>T, c.546G>A) & a novel missense variant (c.169G>T) were found in both premature ovarian failure patients & control subjects in the coding region of GDF9, indicating them as a novel polymorphism
19376510 Reduced GDF-9 expression in cumulus granulosa cells of patients with polycystic ovary syndrome (PCOS) appears to be associated with decreased long-term developmental potential of the oocytes of patients with PCOS.
19366876 GDF-9 stimulates granulosa cell proliferation by stimulating cyclin D(1) and E and suppressing p15(INK4B) and p16(INK4A) via both Smad-dependent and Smad-independent pathways
19111296 Human granulosa-lutein cell GDF-9 expression may play a role in folliculogenesis dependent on follicle-stimulating hormone in the in vitro fertilization cycle.
18854109 The transition from resting to growing follicles leading to the development of secondary follicles showed the normal expression patterns of GDF-9 and AMH.
18162287 This study is the first characterization of purified biologically active human GDF9 and as such is of importance for studies on human fertility.
18006624 phosphorylation state of rhBMP-15 and rhGDF-9 is a determinant of their agonistic and antagonistic activities
17482612 Observational study of gene-disease association. (HuGE Navigator)
17482612 Substitution of hydrophobic amino acid residue alanine for hydrophilic threonine may disrupt growth differentiation factor 9 function in women with premature ovarian failure.
17453295 GDF9 may act as a growth inhibitor in breast cancer.Losing GDF9 during cancer progression may increase its aggressiveness.
17156781 GDF9 mutations may be one explanation for POF, albeit uncommon.
17027369 Observational study of gene-disease association. (HuGE Navigator)
17027369 Mutational screening of the bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes in a population with premature ovarian failure (POF) identified no new mutations.
16954162 new variants in the GDF9 gene that are significantly more common in mothers of DZ twins than controls, suggesting that rare GDF9 variants contribute to the likelihood of DZ twinning.
16645022 Observational study of gene-disease association. (HuGE Navigator)
16645022 although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in premature ovarian failure
16278619 Observational study of gene-disease association. (HuGE Navigator)
16278619 This case-control study revealed eight mutations in the GDF9 gene in women with premature ovarian failure
14970198 BMP-15 and GDF-9 have roles in fertility; critical sequences are determined by mutagenesis
12446716 interaction with bone morphogenetic protein-15
12135884 Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9

AA Sequence

MARPNKFLLWFCCFAWLCFPISLGSQASGGEAQIAASAELESGAMPWSLLQHIDERDRAGLLPALFKVLS      1 - 70
VGRGGSPRLQPDSRALHYMKKLYKTYATKEGIPKSNRSHLYNTVRLFTPCTRHKQAPGDQVTGILPSVEL     71 - 140
LFNLDRITTVEHLLKSVLLYNINNSVSFSSAVKCVCNLMIKEPKSSSRTLGRAPYSFTFNSQFEFGKKHK    141 - 210
WIQIDVTSLLQPLVASNKRSIHMSINFTCMKDQLEHPSAQNGLFNMTLVSPSLILYLNDTSAQAYHSWYS    211 - 280
LHYKRRPSQGPDQERSLSAYPVGEEAAEDGRSSHHRHRRGQETVSSELKKPLGPASFNLSEYFRQFLLPQ    281 - 350
NECELHDFRLSFSQLKWDNWIVAPHRYNPRYCKGDCPRAVGHRYGSPVHTMVQNIIYEKLDSSVPRPSCV    351 - 420
PAKYSPLSVLTIEPDGSIAYKEYEDMIATKCTCR                                        421 - 454
//

Text Mined References (83)

PMID Year Title
26254468 2015 Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-? Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality.
25954833 2015 Single nucleotide polymorphisms in premature ovarian failure-associated genes in a Chinese Hui population.
25368253 2014 Reduced expression of growth and differentiation factor-9 (GDF9) is associated with aggressive behaviour of human clear-cell renal cell carcinoma and poor patient survival.
25253739 2014 Amino acid 72 of mouse and human GDF9 mature domain is responsible for altered homodimer bioactivities but has subtle effects on GDF9:BMP15 heterodimer activities.
25172094 2014 Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome.
25139161 2014 Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization, and embryo quality in humans.
24939957 2014 Identification of a duplication within the GDF9 gene and novel candidate genes for primary ovarian insufficiency (POI) by a customized high-resolution array comparative genomic hybridization platform.
24840335 2014 Recombinant human growth differentiation factor-9 improves oocyte reprogramming competence and subsequent development of bovine cloned embryos.
24438375 2014 Aberrant GDF9 expression and activation are associated with common human ovarian disorders.
24430093 2015 Association of plasma GDF-9 or GDF-15 levels with bone parameters in polycystic ovary syndrome.
24413384 2014 Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells.
23851219 2013 Identification of a mutation in GDF9 as a novel cause of diminished ovarian reserve in young women.
23650403 2013 Growth differentiation factor 9:bone morphogenetic protein 15 (GDF9:BMP15) synergism and protein heterodimerization.
23567549 2013 Granulosa cell tumor mutant FOXL2C134W suppresses GDF-9 and activin A-induced follistatin transcription in primary granulosa cells.
23523567 2013 Essential but differential role of FOXL2wt and FOXL2C134W in GDF-9 stimulation of follistatin transcription in co-operation with Smad3 in the human granulosa cell line COV434.
23382188 2013 Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions.
23060562 2012 Loss of expression of growth differentiation factor-9 (GDF9) in human kidney cancer and regulation of growth and migration of kidney cancer cells by GDF9.
23011157 2012 Expression of CDC6 and GDF-9 and their clinicopathological significances in benign and malignant lesions of the gallbladder.
22825968 2012 Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation.
22234469 2012 Activation of latent human GDF9 by a single residue change (Gly 391 Arg) in the mature domain.
22159313 2012 Growth differentiation factor-9 expression is inversely correlated with an aggressive behaviour in human bladder cancer cells.
21970812 2012 The ratio of growth differentiation factor 9: bone morphogenetic protein 15 mRNA expression is tightly co-regulated and differs between species over a wide range of ovulation rates.
21829661 2011 Growth differentiation factor 9 (GDF9) suppresses follistatin and follistatin-like 3 production in human granulosa-lutein cells.
21669410 2011 Abnormal expression of growth differentiation factor 9 and bone morphogenetic protein 15 in stimulated oocytes during maturation from women with polycystic ovary syndrome.
21632818 2011 Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9.
21496799 2011 Influence of follicular fluid GDF9 and BMP15 on embryo quality.
21226076 2011 Integral role of GDF-9 and BMP-15 in ovarian function.
21116689 2011 Growth and differentiation factor 9 (GDF-9) induces epithelial-mesenchymal transition in prostate cancer cells.
21042764 2010 Growth and differentiation factor-9 promotes adhesive and motile capacity of prostate cancer cells by up-regulating FAK and Paxillin via Smad dependent pathway.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20705511 2010 Identification of novel missense mutations of GDF9 in Chinese women with polycystic ovary syndrome.
20660033 2010 Growth differentiation factor 9 reverses activin A suppression of steroidogenic acute regulatory protein expression and progesterone production in human granulosa-lutein cells.
20547206 2010 Impaired production of BMP-15 and GDF-9 mature proteins derived from proproteins WITH mutations in the proregion.
20458753 2010 GDF-9 promotes the growth of prostate cancer cells by protecting them from apoptosis.
20451184 2010 G546A polymorphism of growth differentiation factor-9 contributes to the poor outcome of ovarian stimulation in women with diminished ovarian reserve.
20427239 2010 Expression of growth-differentiating factor 9 and its type 1 receptor in human ovaries.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20236105 2010 Association study of four key folliculogenesis genes in polycystic ovary syndrome.
20067794 2010 Golgi apparatus casein kinase phosphorylates bioactive Ser-6 of bone morphogenetic protein 15 and growth and differentiation factor 9.
19931079 2010 Growth differentiation factor 9 concentration in the follicular fluid of infertile women with endometriosis.
19846738 2009 Effects of endogenous growth differentiation factor 9 on activin A-induced inhibin B production in human granulosa-lutein cells.
19505950 2009 Extra-ovarian expression and activity of growth differentiation factor 9.
19438907 2010 Analyses of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) mutation in Chinese women with premature ovarian failure.
19423755 2009 Growth differentiation factor 9 enhances activin a-induced inhibin B production in human granulosa cells.
19376510 2010 Expression of growth differentiation factor-9 and bone morphogenetic protein-15 in oocytes and cumulus granulosa cells of patients with polycystic ovary syndrome.
19366876 2009 Effects of growth differentiation factor 9 on cell cycle regulators and ERK42/44 in human granulosa cell proliferation.
19111296 2009 Granulosa-lutein cell growth differentiation factor-9 (GDF-9) messenger RNA and protein expression in in vitro fertilization (IVF) cycles: relation to characteristics of ovulation induction and IVF.
18854109 2008 Growth differentiation factor-9 and anti-Müllerian hormone expression in cultured human follicles from frozen-thawed ovarian tissue.
18633140 2008 The proregion of mouse BMP15 regulates the cooperative interactions of BMP15 and GDF9.
18162287 2008 Characterization of recombinant human growth differentiation factor-9 signaling in ovarian granulosa cells.
18063682 2008 The cooperative effect of growth and differentiation factor-9 and bone morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily through BMP receptor II.
18006624 2008 Phosphorylation of bone morphogenetic protein-15 and growth and differentiation factor-9 plays a critical role in determining agonistic or antagonistic functions.
17482612 2007 Analyses of GDF9 mutation in 100 Chinese women with premature ovarian failure.
17453295 2007 The role of growth differentiation factor-9 (GDF-9) and its analog, GDF-9b/BMP-15, in human breast cancer.
17156781 2007 Growth differentiating factor-9 mutations may be associated with premature ovarian failure.
17027369 2006 Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure.
16954162 2006 Novel variants in growth differentiation factor 9 in mothers of dizygotic twins.
16645022 2006 Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.
16603567 Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16278619 Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure.
16169070 2005 A human protein-protein interaction network: a resource for annotating the proteome.
15607004 2004 A deletion mutation in GDF9 in sisters with spontaneous DZ twins.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15383276 2004 A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease.
15372022 2004 The DNA sequence and comparative analysis of human chromosome 5.
14970198 2004 Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9.
12574210 2003 Growth differentiation factor-9 induces Smad2 activation and inhibin B production in cultured human granulosa-luteal cells.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12446716 2003 Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep.
12135884 2002 Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9.
12050262 2002 Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-stimulated steroidogenesis in human granulosa and theca cells.
11889206 2002 Aberrant expression of growth differentiation factor-9 in oocytes of women with polycystic ovary syndrome.
11788667 2002 Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture.
11604237 2001 Stage-dependent role of growth differentiation factor-9 in ovarian follicle development.
11376106 2001 Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function.
11056243 2000 Mutation analysis of the growth differentiation factor-9 and -9B genes in patients with premature ovarian failure and polycystic ovary syndrome.
10443672 1999 Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis.
10067849 1999 Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles.
9564873 1998 Expression of growth differentiation factor-9 messenger ribonucleic acid in ovarian and nonovarian rodent and human tissues.
8849725 1996 Growth differentiation factor-9 is required during early ovarian folliculogenesis.
8429021 1993 GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines.
7760846 1995 Oocyte-specific expression of growth/differentiation factor-9.