GDF5 (Growth Differentiation Factor 5)
Key regulator of skeletal and joint development; mutations linked to chondrodysplasias and osteoarthritis
Gene Information Card
| Symbol | GDF5 |
|---|---|
| Full Name | Growth Differentiation Factor 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 8200 ncbi.nlm.nih.gov/gene/8200 |
| Ensembl ID | ENSG00000125965 |
| UniProt ID | P43026 |
| OMIM ID | 601146 |
| HGNC ID | 4220 |
| Aliases | BMP14, CDMP1, LAP4, SYNS2 |
Description
GDF5 (Growth Differentiation Factor 5) is a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. It plays a critical role in skeletal and joint development, particularly in the formation of bones, cartilage, and synovial joints. GDF5 regulates chondrogenesis and osteogenesis through signaling via BMP receptors and SMAD proteins. Mutations in GDF5 are associated with various skeletal dysplasias and osteoarthritis susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brachydactyly type C | Loss-of-function mutations in GDF5 disrupt digit formation, leading to shortened or malformed fingers. | ClinVar; OMIM #113100 |
| Acromesomelic dysplasia, Hunter-Thompson type | Homozygous loss-of-function mutations impair limb development, causing severe shortening of limbs. | OMIM #201250 |
| Osteoarthritis susceptibility | Common variants (e.g., rs143383) reduce GDF5 expression in joints, increasing risk of osteoarthritis. | NCBI Gene; GWAS studies |
| Multiple synostoses syndrome 2 | Gain-of-function mutations enhance BMP signaling, leading to joint fusions and synostoses. | OMIM #610017 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 0.3 | Low |
| Cartilage | 2.1 | Medium |
| Lung | 0.1 | Low |
| Brain | 0.0 | Not detected |
| Heart | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Chondrocytes | 2.5 | Primary articular chondrocytes |
| Osteoblasts | 0.8 | Differentiated osteoblasts |
| Fibroblasts | 0.2 | Skin fibroblasts |
| HEK 293 | 0.0 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1129C>T (p.Arg377Ter) | Nonsense | Rare | Loss of function; truncation of protein |
| c.331C>T (p.Arg111Cys) | Missense | Rare | Reduced BMP signaling; associated with brachydactyly type C |
| rs143383 (5' UTR) | SNP | High (allele frequency ~0.5) | Reduced transcriptional activity; risk factor for osteoarthritis |
| c.1466G>A (p.Arg489Gln) | Missense | Rare | Gain of function; causes multiple synostoses syndrome 2 |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish GDF5 activity lead to brachydactyly type C and acromesomelic dysplasia.
Gain of Function (GOF)
Missense mutations that enhance receptor binding or signaling cause multiple synostoses syndrome 2.
Dominant Negative (DN)
Not clearly documented for GDF5; most mutations act via haploinsufficiency or altered signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-beta signaling pathway (KEGG: hsa04350)
• BMP signaling pathway (Reactome: R-HSA-201451)
• Signaling by BMP (Reactome: R-HSA-201451)
Protein Summary
GDF5 is a secreted ligand of the TGF-beta superfamily. The precursor protein undergoes proteolytic processing to generate a mature dimer that binds to BMP receptors (BMPR1A, BMPR1B, BMPR2). It activates SMAD1/5/8 signaling, promoting chondrogenesis and osteogenesis. The protein is essential for joint formation and digit patterning.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GDF5 Knockout HEK293 Cell Line | EDJ-KQ380 | Human | 8200 | Details Get a Quote |
| GDF5 Knockout HeLa Cell Line | EDJ-KQ54832 | Human | 8200 | Details Get a Quote |
| GDF5 Knockout A-549 Cell Line | EDJ-KQ63323 | Human | 8200 | Details Get a Quote |
| GDF5 Knockout HCT 116 Cell Line | EDJ-KQ71793 | Human | 8200 | Details Get a Quote |
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