GDF5 Gene

Name	growth differentiation factor 5
Description	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 the development of numerous tissue and cell types, including cartilage, joints, brown fat, teeth, and the growth of neuronal axons and dendrites. Mutations in this gene are associated with acromesomelic dysplasia, brachydactyly, chondrodysplasia, multiple synostoses syndrome, proximal symphalangism, and susceptibility to osteoarthritis. [provided by RefSeq, Aug 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Growth differentiation factor‐5 (GDF5) is a secreted member of the transforming growth factor‐β superfamily with key roles in skeletal development, joint formation, and cartilage homeostasis. It is expressed in early joint interzones and along developing skeletal elements, where it acts as a pro‐chondrogenic signal that helps establish joint boundaries and regulate the differentiation and maturation of chondrocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Genetic studies have shown that common variants located in the GDF5 promoter, most notably the rs143383 single‐nucleotide polymorphism, significantly influence GDF5 transcription in multiple joint tissues. The risk allele is associated with reduced gene expression, thereby contributing to osteoarthritis susceptibility as well as variation in adult height."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "5"}]}, {"type": "t", "text": " Moreover, rare mutations that alter the receptor‐binding affinities of GDF5 have been linked to skeletal malformations such as brachydactyly type A2 and symphalangism, reflecting not only its critical function in regulating cell fate during limb patterning but also its sensitivity to quantitative alterations in signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition to its roles in embryonic joint development, emerging evidence indicates that GDF5 also modulates repair processes; for example, GDF5 deficiency leads to delayed tendon healing associated with perturbations in cellular recruitment and extracellular matrix remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, the regulation of GDF5 expression is further refined by epigenetic mechanisms, such as DNA methylation at CpG sites created by promoter variants, which in turn modulate the differential allelic expression observed in synovial joint tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Together, these studies underscore the multifaceted role of GDF5 in skeletal growth and joint integrity, and highlight how both genetic and epigenetic alterations in its regulation can have profound effects on musculoskeletal health.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephen H Settle, Ryan B Rountree, Abhishek Sinha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0012-1606(02)00022-2"}], "href": "https://doi.org/10.1016/s0012-1606(02"}, {"type": "t", "text": "00022-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12606286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12606286"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yoshinari Miyamoto, Akihiko Mabuchi, Dongquan Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/2005"}], "href": "https://doi.org/10.1038/2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17384641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17384641"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Serena Sanna, Anne U Jackson, Ramaiah Nagaraja, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants in the GDF5-UQCC region are associated with variation in human height."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.74"}], "href": "https://doi.org/10.1038/ng.74"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18193045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18193045"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lorraine Southam, Julio Rodriguez-Lopez, James M Wilkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An SNP in the 5'-UTR of GDF5 is associated with osteoarthritis susceptibility in Europeans and with in vivo differences in allelic expression in articular cartilage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddm174"}], "href": "https://doi.org/10.1093/hmg/ddm174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17616513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17616513"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kay Chapman, Atsushi Takahashi, Ingrid Meulenbelt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn038"}], "href": "https://doi.org/10.1093/hmg/ddn038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18299287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18299287"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Petra Seemann, Raphaela Schwappacher, Klaus W Kjaer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI25118"}], "href": "https://doi.org/10.1172/JCI25118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16127465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16127465"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A Chhabra, D Tsou, R T Clark, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GDF-5 deficiency in mice delays Achilles tendon healing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Orthop Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0736-0266(03)00049-4"}], "href": "https://doi.org/10.1016/S0736-0266(03"}, {"type": "t", "text": "00049-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12919870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12919870"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Louise N Reynard, Catherine Bui, Elizabeth G Canty-Laird, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr253"}], "href": "https://doi.org/10.1093/hmg/ddr253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21642387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21642387"}]}]}]}
Synonyms	SYM1B, SYNS2, OS5, BMP-14, LAP4, BDA1C, LAP-4, BMP14, CDMP1
Proteins	GDF5_HUMAN
NCBI Gene ID	8200
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GDF5 has 5,867 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for GDF5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GDF5 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GDF5 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of GDF5 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of GDF5 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of GDF5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of GDF5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GDF5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of GDF5 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GDF5 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GDF5 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of GDF5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GDF5 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of GDF5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GDF5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GDF5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of GDF5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with GDF5 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with GDF5 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GDF5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GDF5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GDF5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with GDF5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of GDF5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GDF5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with GDF5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GDF5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving GDF5 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with GDF5 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with GDF5 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GDF5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with GDF5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with GDF5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GDF5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GDF5 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GDF5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GDF5 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing GDF5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GDF5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with GDF5 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of GDF5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with GDF5 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.