GDF3 Gene: Growth Differentiation Factor 3
Key regulator of embryonic development and adipogenesis, implicated in Klippel-Feil syndrome and cancer
Gene Information Card
| Symbol | GDF3 |
|---|---|
| Full Name | Growth Differentiation Factor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 9573 ncbi.nlm.nih.gov/gene/9573 |
| Ensembl ID | ENSG00000184344 |
| UniProt ID | Q9NR23 |
| OMIM ID | 606522 |
| HGNC ID | 4220 |
| Aliases | MCOP6, KFS4, MCOPCB6, VGR-2 |
Description
GDF3 (Growth Differentiation Factor 3) is a member of the transforming growth factor-beta (TGF-β) superfamily. It encodes a secreted ligand that binds to TGF-β receptors, regulating embryonic development, mesoderm formation, and adipocyte differentiation. Mutations in GDF3 are associated with Klippel-Feil syndrome 4 (KFS4) and microphthalmia/coloboma. Altered expression is observed in several cancers, including melanoma and breast cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Klippel-Feil syndrome 4 (KFS4) | Missense mutations impair ligand-receptor signaling, disrupting somitogenesis and vertebral segmentation. | OMIM #616549; PMID: 26026792 |
| Microphthalmia with coloboma 6 (MCOP6) | Loss-of-function variants reduce BMP signaling, affecting eye development. | OMIM #613703; PMID: 21258341 |
| Melanoma | GDF3 overexpression promotes tumor growth and metastasis via TGF-β pathway activation. | COSMIC; PMID: 25605248 |
| Breast cancer | Epigenetic silencing of GDF3 correlates with poor prognosis and invasive phenotype. | PMID: 24154872 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Bone marrow | 8.3 | Low |
| Placenta | 6.7 | Low |
| Testis | 4.2 | Low |
| Skeletal muscle | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression in recombinant systems |
| MCF7 | 3.5 | Low expression; upregulated in invasive sublines |
| A375 | 22.1 | High expression in melanoma cell line |
| HepG2 | 1.2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.401C>T (p.Pro134Leu) | Missense | Rare (0.0004 in gnomAD) | Loss of function; associated with KFS4 |
| c.2T>C (p.Met1Thr) | Start loss | Very rare | Complete loss of protein; linked to MCOP6 |
| c.106G>A (p.Gly36Arg) | Missense | 0.0001 | Reduced BMP signaling activity |
| c.647G>A (p.Arg216His) | Missense | 0.0002 | Uncertain significance; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Pro134Leu) and start-loss variants impair protein secretion or receptor binding, reducing downstream SMAD signaling.
Gain of Function (GOF)
Not well documented; overexpression in melanoma may act as a gain-of-function through increased TGF-β pathway activation.
Dominant Negative (DN)
Some missense variants (e.g., p.Gly36Arg) may form non-functional dimers with wild-type GDF3, interfering with normal signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-beta signaling pathway (KEGG: hsa04350)
• Signaling by TGF-beta family members (Reactome: R-HSA-9006936)
• BMP signaling pathway (Reactome: R-HSA-201451)
Protein Summary
GDF3 is a secreted protein of 366 amino acids (precursor) that undergoes proteolytic processing to generate a mature C-terminal domain containing a conserved cysteine knot motif. It functions as a homodimer or heterodimer with other TGF-β ligands (e.g., GDF1, NODAL) to activate SMAD2/3 and SMAD1/5/8 pathways. GDF3 plays critical roles in mesoderm induction, left-right patterning, and adipogenesis. Dysregulation contributes to congenital vertebral defects, ocular malformations, and tumor progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GDF3 Knockout HEK293 Cell Line | EDJ-KQ6642 | Human | 9573 | Details Get a Quote |
| GDF3 Knockout HeLa Cell Line | EDJ-KQ55199 | Human | 9573 | Details Get a Quote |
| GDF3 Knockout A-549 Cell Line | EDJ-KQ63681 | Human | 9573 | Details Get a Quote |
| GDF3 Knockout HCT 116 Cell Line | EDJ-KQ72143 | Human | 9573 | Details Get a Quote |
