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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GDF6
growth differentiation factor 6
Chromosome 8 Β· 8q22.1
NCBI Gene: 392255Ensembl: ENSG00000156466.11HGNC: HGNC:4221UniProt: A0A0S2A5D6
48PubMed Papers
25Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisHighly Constrained
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of chondrocyte differentiationactivin receptor signaling pathwaymetanephros developmentpositive regulation of DNA-templated transcriptionKlippel-Feil syndrome 1, autosomal dominantisolated microphthalmia 4Leber congenital amaurosis 17Isolated anophthalmia - microphthalmia
✦AI Summary

GDF6 (growth differentiation factor 6) is a member of the bone morphogenetic protein (BMP) family that serves dual functions through distinct molecular domains. The mature BMP domain regulates skeletal development and joint formation by activating SMAD1/5/8 signaling pathways, with enhanced GDF6 activity causing joint fusion disorders like multiple synostoses syndrome 1. The prodomain functions independently as a ligand for CD99, regulating Src kinase activity and cellular proliferation in contexts such as Ewing sarcoma 2. In eye development, GDF6 is essential for controlling retinal size through regulation of apoptosis, with mutations causing microphthalmia in both zebrafish models and human patients 3. GDF6 also promotes angiogenesis and wound healing, with its expression being regulated by miRNA-155-5p from M1-polarized macrophages 4. In cancer, GDF6 exhibits context-dependent roles, functioning as both a tumor suppressor and oncogene across different malignancies through activation of PI3K-Akt/VEGF pathways 5. Additionally, GDF6 contributes to intervertebral disc maintenance by promoting extracellular matrix stability 6 and plays a role in innate immune responses through FTO-mediated m6A modifications 7. The evolutionary significance of GDF6 is highlighted by its regulation through the primate-specific TOSPEAK gene, which controls laryngeal and wrist development 8.

Sources cited
1
Enhanced GDF6 activity causes joint fusion through upregulated BMP signaling and excess chondrogenesis
PMID: 36744814
2
GDF6 prodomain binds CD99 to regulate Src kinase activity and cellular proliferation
PMID: 33147457
3
GDF6 mutations cause microphthalmia through increased apoptosis during retinal development
PMID: 21070663
4
GDF6 promotes angiogenesis and wound healing, regulated by miRNA-155-5p
PMID: 38074896
5
GDF6 has context-dependent roles in cancer through PI3K-Akt/VEGF pathway activation
PMID: 40699648
6
GDF6 promotes extracellular matrix stability in intervertebral disc cells
PMID: 39920317
7
GDF6 contributes to antiviral immunity through FTO-mediated m6A modifications
PMID: 39474078
8
TOSPEAK gene regulates GDF6 enhancers controlling laryngeal and wrist development
PMID: 35885978
Disease Associationsβ“˜25
Klippel-Feil syndrome 1, autosomal dominantOpen Targets
0.78Strong
isolated microphthalmia 4Open Targets
0.75Strong
Leber congenital amaurosis 17Open Targets
0.71Strong
Isolated anophthalmia - microphthalmiaOpen Targets
0.71Strong
multiple synostoses syndromeOpen Targets
0.60Moderate
microphthalmia, isolated, with colobomaOpen Targets
0.58Moderate
microphthalmiaOpen Targets
0.58Moderate
multiple synostoses syndrome 4Open Targets
0.57Moderate
congenital anomaly of kidney and urinary tractOpen Targets
0.44Moderate
congenital hydronephrosisOpen Targets
0.44Moderate
Klippel-Feil syndromeOpen Targets
0.42Moderate
Leber congenital amaurosisOpen Targets
0.37Weak
hearing loss, autosomal recessive 118, with cochlear aplasiaOpen Targets
0.37Weak
isolated Klippel-Feil syndromeOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.36Weak
Hereditary late-onset Parkinson diseaseOpen Targets
0.33Weak
diverticular diseaseOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.26Weak
osteoarthritis, hipOpen Targets
0.21Weak
total hip arthroplastyOpen Targets
0.21Weak
Deafness, autosomal recessive, 118, with cochlear aplasiaUniProt
Klippel-Feil syndrome 1, autosomal dominantUniProt
Leber congenital amaurosis 17UniProt
Microphthalmia, isolated, 4UniProt
Multiple synostoses syndrome 4UniProt
Pathogenic Variants5
NM_001001557.4(GDF6):c.1318_1320del (p.Val440del)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 440
NM_001001557.4(GDF6):c.986_1005del (p.Pro329fs)Likely pathogenic
Klippel-Feil syndrome 1, autosomal dominant
β˜…β˜†β˜†β˜†2021β†’ Residue 329
NM_001001557.4(GDF6):c.1330T>A (p.Tyr444Asn)Pathogenic
Multiple synostoses syndrome 4
β˜…β˜†β˜†β˜†2018β†’ Residue 444
NM_001001557.4(GDF6):c.73C>T (p.Gln25Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 25
NM_001001557.4(GDF6):c.876G>Y (p.Glu292Asp)Pathogenic
Leber congenital amaurosis 17
β˜†β˜†β˜†β˜†2013β†’ Residue 292
View on ClinVar β†—
Related Genes
ACVR2BProtein interaction96%BMPR1AProtein interaction96%BMPR1BProtein interaction96%BMPR2Protein interaction95%CHRDProtein interaction95%NOGProtein interaction95%
Tissue Expression6 tissues
Heart
100%
Brain
20%
Liver
18%
Bone Marrow
9%
Lung
5%
Ovary
5%
Gene Interaction Network
Click a node to explore
GDF6ACVR2BBMPR1ABMPR1BBMPR2CHRDNOG
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6KF10
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.34Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.15 [0.07–0.34]
RankingsWhere GDF6 stands among ~20K protein-coding genes
  • #9,077of 20,598
    Most Researched48
  • #3,586of 5,498
    Most Pathogenic Variants5
  • #1,485of 17,882
    Most Constrained (LOEUF)0.34 Β· top 10%
Genes detectedGDF6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Dual-Faced Role of GDF6 in Cancer: Mechanistic Insights into Its Context-Dependent Regulation of Metastasis and Immune Evasion Across Human Malignancies.
PMID: 40699648
Curr Issues Mol Biol Β· 2025
1.00
2
The GDF6-FTO axis modulates the innate immune and inflammatory response to human respiratory syncytial virus.
PMID: 39474078
iScience Β· 2024
0.90
3
Defective Joint Development and Maintenance in GDF6-Related Multiple Synostoses Syndrome.
PMID: 36744814
J Bone Miner Res Β· 2023
0.80
4
Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing.
PMID: 38074896
Mol Ther Nucleic Acids Β· 2023
0.70
5
Effects of GDF6 on active protein synthesis by cells of degenerated intervertebral disc.
PMID: 39920317
Eur Spine J Β· 2025
0.60