GDF9 (growth differentiation factor 9)

Gene

• Entrez ID: 2661
• Gene name: Growth differentiation factor 9
• Gene symbol: GDF9
• Synonyms (NCBI Gene): POF14
• Chromosome: 5
• Chromosome location: 5q31.1
• Summary: This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1216260561	G>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017790	hsa-miR-335-5p	Microarray	18185580
MIRT019338	hsa-miR-148b-3p	Microarray	17612493
MIRT1015749	hsa-miR-124	CLIP-seq
MIRT1015750	hsa-miR-1244	CLIP-seq
MIRT1015751	hsa-miR-199a-3p	CLIP-seq
MIRT1015752	hsa-miR-199b-3p	CLIP-seq
MIRT1015753	hsa-miR-3129-5p	CLIP-seq
MIRT1015754	hsa-miR-3622a-5p	CLIP-seq
MIRT1015755	hsa-miR-4423-3p	CLIP-seq
MIRT1015756	hsa-miR-4432	CLIP-seq
MIRT1015757	hsa-miR-4789-3p	CLIP-seq
MIRT1015758	hsa-miR-499-5p	CLIP-seq
MIRT1015759	hsa-miR-506	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001555	Process	Oocyte growth	IEA
GO:0005125	Function	Cytokine activity	IBA
GO:0005125	Function	Cytokine activity	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0007178	Process	Cell surface receptor protein serine/threonine kinase signaling pathway	IBA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS	7760846
GO:0007292	Process	Female gamete generation	IEA
GO:0007292	Process	Female gamete generation	TAS	7760846, 8849725
GO:0008083	Function	Growth factor activity	IEA
GO:0008083	Function	Growth factor activity	TAS	8849725
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	19366876
GO:0030308	Process	Negative regulation of cell growth	IEA
GO:2000870	Process	Regulation of progesterone secretion	IDA	12050262
GO:2000870	Process	Regulation of progesterone secretion	IMP	20660033

Other IDs

• MIM: 601918
• HGNC: 4224
• e!Ensembl: ENSG00000164404

Protein

• UniProt ID: O60383
• Protein name: Growth/differentiation factor 9 (GDF-9)
• Protein function: Required for ovarian folliculogenesis. Promotes primordial follicle development. Stimulates granulosa cell proliferation. Promotes cell transition from G0/G1 to S and G2/M phases, through an increase of CCND1 and CCNE1 expression, and RB1 phosph
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00019	TGF_beta	352 → 453	Transforming growth factor beta like domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in ovarian granulosa cells. Present in oocytes of primary follicles (at protein level). {ECO:0000269|PubMed:10443672, ECO:0000269|PubMed:12050262}.
• Sequence:

  MARPNKFLLWFCCFAWLCFPISLGSQASGGEAQIAASAELESGAMPWSLLQHIDERDRAG
  LLPALFKVLSVGRGGSPRLQPDSRALHYMKKLYKTYATKEGIPKSNRSHLYNTVRLFTPC
  TRHKQAPGDQVTGILPSVELLFNLDRITTVEHLLKSVLLYNINNSVSFSSAVKCVCNLMI
  KEPKSSSRTLGRAPYSFTFNSQFEFGKKHKWIQIDVTSLLQPLVASNKRSIHMSINFTCM
  KDQLEHPSAQNGLFNMTLVSPSLILYLNDTSAQAYHSWYSLHYKRRPSQGPDQERSLSAY
  PVGEEAAEDGRSSHHRHRRGQETVSSELKKPLGPASFNLSEYFRQFLLPQNECELHDFRL
  SFSQLKWDNWIVAPHRYNPRYCKGDCPRAVGHRYGSPVHTMVQNIIYEKLDSSVPRPSCV
  PAKYSPLSVLTIEPDGSIAYKEYEDMIATKCTCR

• Sequence length: 454

Pathways

KEGG:

Cytokine-cytokine receptor interaction

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Genetic non-acquired premature ovarian failure	Likely pathogenic	rs751894227	RCV001661766	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature ovarian failure 14	Likely pathogenic; Pathogenic	rs2150042519, rs2532351267, rs373477788, rs745755437, rs1216260561	RCV001729991 RCV003991742 RCV004595815 RCV004595816 RCV000656489	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GDF9-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN FAILURE, PREMATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYSTIC OVARY SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature ovarian failure	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	23011157		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	22159313		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	35436939	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	23011157	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	22159313		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	25368253		★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	28831646	Associate	★☆☆☆☆ Found in Text Mining only
Gallbladder Carcinoma	Gallbladder cancer	BEFREE	23011157		★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis, 45,X	Gonadal Dysgenesis	BEFREE	31151408		★☆☆☆☆ Found in Text Mining only
granulosa cell tumor	Granulosa Cell Tumor	BEFREE	23567549		★☆☆☆☆ Found in Text Mining only
Hereditary hemochromatosis	Hereditary Hemochromatosis	BEFREE	29028960		★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	BEFREE	22825968		★☆☆☆☆ Found in Text Mining only
Hyperplasia	Hyperplasia	Pubtator	23011157	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Neoplasm	Kidney Neoplasm	BEFREE	23060562		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	23011157	Inhibit	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of kidney	Kidney Cancer	BEFREE	23060562		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	20458753, 21042764		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	22159313		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	17453295		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	22159313, 23060562		★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Primary ovarian failure	Ovarian Failure	Orphanet			★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Ovarian diseases	Pubtator	20451184	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Ovarian Diseases	BEFREE	24438375		★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	BEFREE	11056243, 16278619, 16645022, 16719785, 17027369, 17156781, 17482612, 20547206, 20705511, 24438375, 24939957, 25954833, 29044499, 29916099, 31392662, 31607184		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Failure, Premature	Ovarian Failure	LHGDN	16278619, 16645022, 17482612		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Failure, Premature	Ovarian Failure	GENOMICS_ENGLAND_DG	17156781		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	33036707, 38358476	Associate	★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	11056243, 11889206, 19376510, 20236105, 20705511, 21669410, 22825968, 23912750, 24438375, 25172094, 28860512, 28903889, 31211369, 31287539		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	19376510, 20236105, 21669410, 22825968, 23912750, 31287539	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	CTD_human_DG	22825968		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	25172094	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature Menopause	Premature Menopause	BEFREE	11056243, 16278619, 16645022, 16719785, 17027369, 17156781, 17482612, 20705511, 24438375, 25954833, 29044499, 31392662, 31607184		★☆☆☆☆ Found in Text Mining only
PREMATURE OVARIAN FAILURE 14	Premature Ovarian Failure	UNIPROT_DG	16278619, 16645022, 16954162, 17156781, 17482612, 19438907, 29044499		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary physiologic amenorrhea	Physiologic Amenorrhea	BEFREE	16278619		★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	20458753, 21042764		★☆☆☆☆ Found in Text Mining only
Renal carcinoma	Renal Carcinoma	BEFREE	23060562		★☆☆☆☆ Found in Text Mining only
Sclerocystic Ovaries	Sclerocystic Ovaries	CTD_human_DG	22825968		★☆☆☆☆ Found in Text Mining only
Secondary physiologic amenorrhea	Secondary Physiologic Amenorrhea	BEFREE	16278619		★☆☆☆☆ Found in Text Mining only
Shwachman syndrome	Shwachman Syndrome	BEFREE	31147040		★☆☆☆☆ Found in Text Mining only
Subfertility	Subfertility	BEFREE	28903889		★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner Syndrome	BEFREE	31151408		★☆☆☆☆ Found in Text Mining only