GDF2 (Growth Differentiation Factor 2)
Bone Morphogenetic Protein 9 (BMP9) – Key Regulator of Angiogenesis and Iron Homeostasis
Gene Information Card
| Symbol | GDF2 |
|---|---|
| Full Name | Growth Differentiation Factor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q11.22 |
| NCBI Gene ID | 2658 ncbi.nlm.nih.gov/gene/2658 |
| Ensembl ID | ENSG00000107864 |
| UniProt ID | Q9UK05 |
| OMIM ID | 605120 |
| HGNC ID | 4223 |
| Aliases | BMP9, BMP-9, HHT5, MGC117399 |
Description
GDF2 (Growth Differentiation Factor 2) encodes bone morphogenetic protein 9 (BMP9), a member of the TGF-beta superfamily. BMP9 is a circulating ligand that binds to ALK1 (ACVRL1) and BMPR2 receptors, regulating angiogenesis, endothelial cell quiescence, and iron homeostasis via hepcidin expression. Loss-of-function mutations in GDF2 cause hereditary hemorrhagic telangiectasia type 5 (HHT5), characterized by vascular malformations and epistaxis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Hemorrhagic Telangiectasia Type 5 (HHT5) | Loss-of-function mutations in GDF2 impair BMP9/ALK1 signaling, leading to defective endothelial cell junction integrity and abnormal angiogenesis. | OMIM #615506; ClinVar; NCBI |
| Pulmonary Arterial Hypertension (PAH) | Reduced BMP9 levels or activity contribute to pulmonary vascular remodeling via disrupted BMPR2 signaling. | ClinVar; NCBI; OMIM |
| Iron-refractory Iron Deficiency Anemia (IRIDA) | BMP9 regulates hepcidin; GDF2 mutations may alter systemic iron homeostasis. | UniProt; NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Lung | 3.1 | Low |
| Kidney | 1.8 | Low |
| Heart | 0.9 | Not detected |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | 15.2 | High expression |
| HUVEC (umbilical vein endothelial) | 2.4 | Low expression |
| A549 (lung carcinoma) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.988C>T (p.Arg330*) | Nonsense | Rare | Loss of function; truncation of mature BMP9 domain |
| c.1121G>A (p.Arg374His) | Missense | Rare | Impaired receptor binding and signaling |
| c.1061G>A (p.Cys354Tyr) | Missense | Rare | Disrupts disulfide bond; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg330*, p.Cys354Tyr) that reduce or abolish BMP9 secretion, receptor binding, or downstream SMAD signaling.
Gain of Function (GOF)
Not reported in GDF2.
Dominant Negative (DN)
Not established; HHT5 inheritance is autosomal dominant with haploinsufficiency as the proposed mechanism.
View complete mutation data：
Gene Ontology (GO)
Pathways
• BMP signaling pathway (Reactome: R-HSA-201451)
• TGF-beta signaling pathway (KEGG: hsa04350)
• Signaling by BMP (Reactome: R-HSA-201451)
• Hepcidin regulation by BMP/SMAD (Reactome: R-HSA-8956321)
Protein Summary
BMP9 (GDF2) is a secreted homodimeric ligand of the TGF-beta superfamily. Synthesized primarily in the liver, it circulates as a latent complex. Upon proteolytic activation, BMP9 binds with high affinity to ALK1 and BMPR2, activating SMAD1/5/8 signaling. It promotes endothelial cell quiescence, maintains vascular integrity, and induces hepcidin expression in hepatocytes to regulate iron absorption. Mutations cause HHT5 and contribute to PAH.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GDF2 Knockout HEK293 Cell Line | EDJ-KQ4694 | Human | 2658 | Details Get a Quote |
| GDF2 Knockout HeLa Cell Line | EDJ-KQ53323 | Human | 2658 | Details Get a Quote |
| GDF2 Knockout A-549 Cell Line | EDJ-KQ61806 | Human | 2658 | Details Get a Quote |
| GDF2 Knockout HCT 116 Cell Line | EDJ-KQ70292 | Human | 2658 | Details Get a Quote |
