GDF3 (growth differentiation factor 3)

Gene

• Entrez ID: 9573
• Gene name: Growth differentiation factor 3
• Gene symbol: GDF3
• Synonyms (NCBI Gene): KFS3, MCOP7, MCOPCB6
• Chromosome: 12
• Chromosome location: 12p13.31
• 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
rs140926412	G>A,T	Likely-benign, pathogenic	Missense variant, coding sequence variant
rs146973734	C>T	Pathogenic	Missense variant, coding sequence variant
rs387906945	A>C,G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs387906946	G>A	Pathogenic	Missense variant, coding sequence variant
rs780787386	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT736570	hsa-miR-483-3p	Luciferase reporter assay, Western blotting, Microarray, Immunohistochemistry (IHC), qRT-PCR	22223106

Transcription factors

Transcription factor	Regulation	Reference
NANOG	Unknown	22963770

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	IMP	19864492
GO:0001654	Process	Eye development	IMP	19864492
GO:0001701	Process	In utero embryonic development	IEA
GO:0002021	Process	Response to dietary excess	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	IDA	21805089
GO:0005737	Component	Cytoplasm	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007492	Process	Endoderm development	IEA
GO:0007498	Process	Mesoderm development	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0010453	Process	Regulation of cell fate commitment	IDA	18823971
GO:0019901	Function	Protein kinase binding	IPI	21805089
GO:0030509	Process	BMP signaling pathway	IBA
GO:0030514	Process	Negative regulation of BMP signaling pathway	IDA	18823971
GO:0030903	Process	Notochord development	IEA
GO:0032525	Process	Somite rostral/caudal axis specification	IEA
GO:0045600	Process	Positive regulation of fat cell differentiation	IEA
GO:0045600	Process	Positive regulation of fat cell differentiation	ISS
GO:0045605	Process	Negative regulation of epidermal cell differentiation	IDA	18823971
GO:0045662	Process	Negative regulation of myoblast differentiation	IEA
GO:0048513	Process	Animal organ development	IEA
GO:0048859	Process	Formation of anatomical boundary	IEA
GO:0090009	Process	Primitive streak formation	IEA
GO:0090092	Process	Regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	IEA

Other IDs

• MIM: 606522
• HGNC: 4218
• e!Ensembl: ENSG00000184344

Protein

• UniProt ID: Q9NR23
• Protein name: Growth/differentiation factor 3 (GDF-3)
• Protein function: Growth factor involved in early embryonic development and adipose-tissue homeostasis. During embryogenesis controls formation of anterior visceral endoderm and mesoderm and the establishment of anterior-posterior identity through a receptor comp
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00019	TGF_beta	263 → 363	Transforming growth factor beta like domain	Domain

• Sequence:

  MLRFLPDLAFSFLLILALGQAVQFQEYVFLQFLGLDKAPSPQKFQPVPYILKKIFQDREA
  AATTGVSRDLCYVKELGVRGNVLRFLPDQGFFLYPKKISQASSCLQKLLYFNLSAIKERE
  QLTLAQLGLDLGPNSYYNLGPELELALFLVQEPHVWGQTTPKPGKMFVLRSVPWPQGAVH
  FNLLDVAKDWNDNPRKNFGLFLEILVKEDRDSGVNFQPEDTCARLRCSLHASLLVVTLNP
  DQCHPSRKRRAAIPVPKLSCKNLCHRHQLFINFRDLGWHKWIIAPKGFMANYCHGECPFS
  LTISLNSSNYAFMQALMHAVDPEIPQAVCIPTKLSPISMLYQDNNDNVILRHYEDMVVDE
  CGCG

• Sequence length: 364

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CAMPTOCORMIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOBOMATOUS MICROPHTHALMIA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL CYSTIC EYEBALL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EDEMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GDF3-related disorder	Benign; Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART DEFECTS, CONGENITAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hemivertebrae	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Isolated microphthalmia 7	Benign; Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KLIPPEL-FEIL SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Klippel-Feil syndrome 3, autosomal dominant	Likely benign; Benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MICROPHTHALMIA AND MENTAL DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 7	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmia, isolated, with coloboma 6	Conflicting classifications of pathogenicity; Uncertain significance; Benign; Likely benign	ClinVar ClinVar, Disgenet, GenCC ClinVar, Disgenet, GenCC	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MICROPHTHALMIA/COLOBOMA 6	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMOS CO-OCCURRENT WITH CONGENITAL OCULAR COLOBOMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Missing ribs	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Scoliosis	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Supernumerary ribs	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anus, Imperforate	Imperforate anus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arnold-Chiari Malformation, Type I	Arnold-Chiari malformation	BEFREE	23620759		★☆☆☆☆ Found in Text Mining only
Bilateral microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	22488170, 22750649		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	16228988, 25127259	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	22488170	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	27803451	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Embryonal	Embryonal carcinoma	Pubtator	22963770, 27803451	Associate	★☆☆☆☆ Found in Text Mining only
Coloboma	Coloboma	Pubtator	24281366	Associate	★☆☆☆☆ Found in Text Mining only
Coloboma of the Retina	Retinal coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colobomatous microphthalmia	Microphthalmia With Coloboma	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital coloboma of iris	Congenital Coloboma Of Iris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	BEFREE	24859618		★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital torticollis	Congenital Torticollis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	19864492		★☆☆☆☆ Found in Text Mining only
Diabetes Gestational	Gestational diabetes	Pubtator	35547007	Stimulate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	22223106		★☆☆☆☆ Found in Text Mining only
Ectopic anus	Ectopic anus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Embryonal Neoplasm	Embryonal Neoplasm	CTD_human_DG	16168501		★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	BEFREE	19690622		★☆☆☆☆ Found in Text Mining only
Fundus coloboma	Fundus Coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Germ cell tumor	Tumor	BEFREE	14990856, 19396148		★☆☆☆☆ Found in Text Mining only
Germ cell tumor	Tumor	CTD_human_DG	16168501		★☆☆☆☆ Found in Text Mining only
Hemiplegia/hemiparesis	Hemiplegia/hemiparesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of optic disc	Hypoplasia Of Optic Disc	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Isolated Klippel-Feil syndrome	Isolated Klippel-Feil Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Isolated microphthalmia-anophthalmia-coloboma	Isolated Microphthalmia-Anophthalmia-Coloboma	Orphanet			★☆☆☆☆ Found in Text Mining only
Klippel-Feil Syndrome	Klippel Feil syndrome	BEFREE	19864492, 23620759, 26238661		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Klippel-Feil Syndrome	Klippel Feil syndrome	ORPHANET_DG	19864492		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Klippel-Feil Syndrome	Klippel Feil syndrome	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Klippel-Feil Syndrome	Klippel Feil syndrome	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KLIPPEL-FEIL SYNDROME 3, AUTOSOMAL DOMINANT	Klippel Feil syndrome	GENOMICS_ENGLAND_DG	19864492		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
KLIPPEL-FEIL SYNDROME 3, AUTOSOMAL DOMINANT	Klippel Feil syndrome	UNIPROT_DG	19864492		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
KLIPPEL-FEIL SYNDROME 3, AUTOSOMAL DOMINANT	Klippel Feil syndrome	CTD_human_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
KLIPPEL-FEIL SYNDROME, AUTOSOMAL DOMINANT	Klippel Feil syndrome	BEFREE	23620759		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	22488170, 22750649		★☆☆☆☆ Found in Text Mining only
MICROPHTHALMIA, ISOLATED 1	Microphthalmia	ORPHANET_DG	19864492		★☆☆☆☆ Found in Text Mining only
MICROPHTHALMIA, ISOLATED 7	Microphthalmia	UNIPROT_DG	19864492		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 7	Microphthalmia	GENOMICS_ENGLAND_DG	19864492		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 7	Microphthalmia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 7	Microphthalmia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 6	Microphthalmia With Coloboma	GENOMICS_ENGLAND_DG	19864492		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 6	Microphthalmia With Coloboma	UNIPROT_DG	19864492		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 6	Microphthalmia With Coloboma	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 6	Microphthalmia With Coloboma	CTD_human_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Microphthalmos	Microphthalmos	Pubtator	24281366	Associate	★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microphthalmos, Autosomal Recessive	Microphthalmos	ORPHANET_DG	19864492		★☆☆☆☆ Found in Text Mining only
Neck webbing	Neck Webbing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms, Embryonal and Mixed	Neoplasm	CTD_human_DG	16168501		★☆☆☆☆ Found in Text Mining only
Neoplasms, Germ Cell and Embryonal	Neoplasm	CTD_human_DG	16168501		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	15358131, 18480259		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	26474449	Associate	★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	BEFREE	30401983		★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	Pubtator	30401983	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seminoma	Seminoma	Pubtator	16228988	Associate	★☆☆☆☆ Found in Text Mining only
Seminoma	Seminoma	BEFREE	16424014		★☆☆☆☆ Found in Text Mining only
Spina Bifida	Spina Bifida	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sprengel deformity	Sprengel Deformity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Testicular Germ Cell Tumor	Testicular germ cell tumor	Pubtator	17167184, 27803451	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only