GDF2 growth differentiation factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GDF2provided by HGNC
Official Full Name: growth differentiation factor 2provided by HGNC
Primary source: HGNC:HGNC:4217
See related: Ensembl:ENSG00000263761 MIM:605120
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BMP9; HHT5; BMP-9
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 gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates cartilage and bone development, angiogenesis and differentiation of cholinergic central nervous system neurons. Mutations in this gene are associated with hereditary hemorrhagic telangiectasia. [provided by RefSeq, Jul 2016]
Expression: Restricted expression toward liver (RPKM 6.7) See more
Orthologs: mouse all

Genomic context

Location:: 10q11.22

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	10	NC_000010.11 (47322490..47327588)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (48413092..48416853, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in heritable pulmonary arterial hypertension.
Title: Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.
Low BMP9 expression is associated with breast cancer.
Title: BMP9 inhibits the growth of breast cancer cells by downregulation of the PI3K/Akt signaling pathway.
BMP-9 was found the most effective to induce osteogenic transdifferentiation of fat tissue in vitro
Title: Osseous differentiation of human fat tissue grafts: From tissue engineering to tissue differentiation.
Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia.
Title: Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia.
levels of the angiogenesis mediators endoglin, HB-EGF, BMP-9 and FGF-2 in patients with severe sepsis and septic shock
Title: Circulating levels of the angiogenesis mediators endoglin, HB-EGF, BMP-9 and FGF-2 in patients with severe sepsis and septic shock.
BMP9 is highly expressed in bladder cancer cells. BMP9 promotes bladder cancer cell proliferation and migration through up-regulation of lncRNA UCA1.
Title: BMP9 Promotes the Proliferation and Migration of Bladder Cancer Cells through Up-Regulating lncRNA UCA1.
Bone morphogenetic protein 9 (BMP9) was identified as a target of miR-149 in MG63 cells, and BMP9 expression was negatively correlated with miR149 level in osteosarcoma clinical samples. miR-149 promotes osteosarcoma progression via targeting BMP9.
Title: miR-149 promotes human osteocarcinoma progression via targeting bone morphogenetic protein 9 (BMP9).
The binding free energies indicate that ALK-3 preferably binds to BMP-2 instead of BMP-9. The structural analysis shows that ALK-3 binding with BMP-2 occurs in a perfectly symmetry pathway, whereas this symmetry is lost for possible ALK-3 interactions with BMP-9
Title: BMP-2 and BMP-9 binding specificities with ALK-3 in aqueous solution with dynamics.
The BMP9-induced phosphorylation of Smad1/5/8 was increased with the overexpression of RUNX3, and yet was decreased with the knockdown of RUNX3. Collectively, our findings suggest that RUNX3 is an essential modulator of the BMP9-induced osteoblast lineage differentiation of mesenchymal stem cells (MSCs).
Title: RUNX3 plays an important role in mediating the BMP9-induced osteogenic differentiation of mesenchymal stem cells.
BMP9 is overexpressed in hepatic stellate cells in a cohort of liver fibrosis patients.
Title: Targeting secreted cytokine BMP9 gates the attenuation of hepatic fibrosis.

Submit: New GeneRIF Correction See all GeneRIFs (66)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Telangiectasia, hereditary hemorrhagic, type 5 MedGen: C3809710 OMIM: 615506 GeneReviews: Hereditary Hemorrhagic Telangiectasia	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated (2016-10-13) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated (2016-10-13) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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ALK1 signaling events, organism-specific biosystem (from Pathway Interaction Database)
ALK1 signaling events, organism-specific biosystem
ALK1 signaling events

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:480542

NoName (e-PCR)
- UniSTS:482109

GDF2_330.2 (e-PCR)
- UniSTS:280695

Homology

Homologs of the GDF2 gene: The GDF2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 209 organisms have orthologs with human gene GDF2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
growth factor activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
transforming growth factor beta receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
BMP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
BMP signaling pathway	TAS Traceable Author Statement more info
SMAD protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
activin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
blood vessel morphogenesis	IDA Inferred from Direct Assay more info	PubMed
branching involved in blood vessel morphogenesis	IDA Inferred from Direct Assay more info	PubMed
cartilage development	TAS Traceable Author Statement more info	PubMed
cell development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular iron ion homeostasis	TAS Traceable Author Statement more info	PubMed
cellular response to BMP stimulus	IDA Inferred from Direct Assay more info	PubMed
negative regulation of DNA biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of DNA replication	TAS Traceable Author Statement more info	PubMed
negative regulation of angiogenesis	TAS Traceable Author Statement more info	PubMed
negative regulation of blood vessel endothelial cell migration	TAS Traceable Author Statement more info	PubMed
negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
negative regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
negative regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
ossification	TAS Traceable Author Statement more info	PubMed
osteoblast differentiation	IEA Inferred from Electronic Annotation more info
pathway-restricted SMAD protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cartilage development	IEA Inferred from Electronic Annotation more info
positive regulation of endothelial cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of pathway-restricted SMAD protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of pathway-restricted SMAD protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of signaling receptor activity	IEA Inferred from Electronic Annotation more info
vasculogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell	IEA Inferred from Electronic Annotation more info
extracellular exosome	HDA more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: growth/differentiation factor 2

Names: bone morphogenetic protein 9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033916.1 RefSeqGene

Range

5001..10099

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_016204.3 → NP_057288.1 growth/differentiation factor 2 preproprotein

See identical proteins and their annotated locations for NP_057288.1

Status: REVIEWED

Source sequence(s)

AF188285, AK314956, AL731561

Consensus CDS

CCDS73118.1

UniProtKB/Swiss-Prot

Q9UK05

UniProtKB/TrEMBL

B2RC63

Related

ENSP00000463051.1, ENST00000581492.2

Conserved Domains (2) summary

pfam00019
Location:326 → 428

TGF_beta; Transforming growth factor beta like domain

pfam00688
Location:76 → 257

TGFb_propeptide; TGF-beta propeptide