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
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Genomic context

Location:: 10q11.22

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	10	NC_000010.11 (47322454..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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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 Functions

What's a GeneRIF?

Bone morphogenetic protein 9, and its genetic variants contribute to susceptibility of idiopathic pulmonary arterial hypertension.
Title: Bone morphogenetic protein 9, and its genetic variants contribute to susceptibility of idiopathic pulmonary arterial hypertension.
lncRNA Rmst acts as an important mediator of BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by antagonizing Notch-targeting microRNAs.
Title: lncRNA Rmst acts as an important mediator of BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by antagonizing Notch-targeting microRNAs.
Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension.
Title: Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension.
Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases.
Title: Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases.
Homozygous GDF2-Related Hereditary Hemorrhagic Telangiectasia in a Chinese Family.
Title: Homozygous GDF2-Related Hereditary Hemorrhagic Telangiectasia in a Chinese Family.
BMP9/10 in Pulmonary Vascular Complications of Liver Disease.
Title: BMP9/10 in Pulmonary Vascular Complications of Liver Disease.
Study findings suggest that fused suture progenitor cells have elevated osteogenic potential. BMP9 could regulate the expression of multiple osteoblast and osteoclast differentiation-related genes, and NELL-1, in both suture progenitor cells, indicating that BMP9 may play a role in craniosynostosis.
Title: Differential Responsiveness to BMP9 between Patent and Fused Suture Progenitor Cells from Craniosynostosis Patients.
Hepatic BMP9 expression was down-regulated in patients who are diabetic. BMP9 overexpression ameliorated triglyceride accumulation and inhibited the expression of lipogenic genes in HepG2 cells treated with a fatty acid mixture. BMP9 is an important regulator of hepatic glucose and lipid metabolism.
Title: Role of bone morphogenetic protein-9 in the regulation of glucose and lipid metabolism.
Findings demonstrate that GDF2 mutations result in BMP9 loss of function and are likely causal for pulmonary arterial hypertension. These mutations lead to reduced circulating levels of both BMP9 and BMP10.
Title: Characterization of GDF2 Mutations and Levels of BMP9 and BMP10 in Pulmonary Arterial Hypertension.
CRISPR/Cas9-mediated deletion of EGFL7 highlights the critical role of EGFL7 in BMP9-induced endothelial sprouting and the promotion of angiogenesis.
Title: EGFL7 Mediates BMP9-Induced Sprouting Angiogenesis of Endothelial Cells Derived from Human Embryonic Stem Cells.

Submit: New GeneRIF Correction See all GeneRIFs (87)

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)

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: 265 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

Process	Evidence Code	Pubs
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
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 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
vasculogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
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

4965..10099

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_016204.4 → 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, ENST00000581492.3

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