GDNF Gene

HGNC Family	Endogenous ligands
Name	glial cell derived neurotrophic factor
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. The recombinant form of this protein, a highly conserved neurotrophic factor, was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. This protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Mutations in this gene may be associated with Hirschsprung disease and Tourette syndrome. This gene encodes multiple protein isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Glial cell line‐derived neurotrophic factor (GDNF) is a pivotal secreted molecule that plays diverse roles during development and in adult tissue maintenance. In the developing kidney, GDNF is produced by the metanephric mesenchyme and serves as a paracrine signal by binding to the RET receptor on the ureteric bud. This interaction is essential for ureteric bud induction, branching morphogenesis, and proper kidney formation, with GDNF participating in positive feedback loops with other factors such as Wnt11."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the testis, GDNF signaling through the RET/GFRA1 receptor complex is critical for the self‐renewal of spermatogonial stem cells; loss or reduction of GDNF activity disrupts proliferation and maintenance of these progenitors, thereby affecting spermatogenesis and male fertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the enteric nervous system, GDNF is required for directing the migration of neural crest–derived progenitors into the gut wall, ensuring proper colonization and establishment of enteric neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, alterations in GDNF‐immunoreactive nerve fiber density have been associated with changes in visceral sensory function, suggesting that GDNF also contributes to the functional organization of gut innervation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the adult brain, GDNF functions as a powerful neurotrophic factor that protects catecholaminergic neurons from toxic insults and promotes their long‐term survival, underscoring its therapeutic potential in neurodegenerative conditions such as Parkinson’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence indicates that GDNF expression is subject to regulation by signals from the microenvironment. For example, TLR2‐dependent pathways in the gut are involved in modulating smooth muscle GDNF levels and RET signaling, thereby impacting enteric nervous system structure and gastrointestinal motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In parallel, members of the GDNF family such as artemin also play roles in guiding sympathetic nerve projections and promoting target innervation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight GDNF’s multifaceted functions in organogenesis, neural migration, stem cell maintenance, and neuronal survival, making it a key molecule in both developmental biology and potential clinical therapies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Arindam Majumdar, Seppo Vainio, Andreas Kispert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.00520"}], "href": "https://doi.org/10.1242/dev.00520"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12783789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12783789"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M Albert Basson, Simge Akbulut, Judy Watson-Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2004.12.004"}], "href": "https://doi.org/10.1016/j.devcel.2004.12.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15691764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15691764"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Odyssé Michos, Lia Panman, Kristina Vintersten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.01251"}], "href": "https://doi.org/10.1242/dev.01251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15201225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15201225"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Cathy K Naughton, Sanjay Jain, Amy M Strickland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.105.047365"}], "href": "https://doi.org/10.1095/biolreprod.105.047365"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16237148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16237148"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jon M Oatley, Mary R Avarbock, Ralph L Brinster "}, {"type": "b", "children": [{"type": "t", "text": "Glial cell line-derived neurotrophic factor regulation of genes essential for self-renewal of mouse spermatogonial stem cells is dependent on Src family kinase signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703474200"}], "href": "https://doi.org/10.1074/jbc.M703474200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17597063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17597063"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Dipa Natarajan, Camelia Marcos-Gutierrez, Vassilis Pachnis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Requirement of signalling by receptor tyrosine kinase RET for the directed migration of enteric nervous system progenitor cells during mammalian embryogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.129.22.5151"}], "href": "https://doi.org/10.1242/dev.129.22.5151"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12399307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12399307"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "C L H Chan, P Facer, J B Davis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0140-6736(03)12392-6"}], "href": "https://doi.org/10.1016/s0140-6736(03"}, {"type": "t", "text": "12392-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12573376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12573376"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Alberto Pascual, María Hidalgo-Figueroa, José I Piruat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absolute requirement of GDNF for adult catecholaminergic neuron survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn.2136"}], "href": "https://doi.org/10.1038/nn.2136"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18536709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18536709"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Paola Brun, Maria Cecilia Giron, Marsela Qesari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2013.08.047"}], "href": "https://doi.org/10.1053/j.gastro.2013.08.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23994200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23994200"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yutaka Honma, Toshiyuki Araki, Scott Gianino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Artemin is a vascular-derived neurotropic factor for developing sympathetic neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(02)00774-2"}], "href": "https://doi.org/10.1016/s0896-6273(02"}, {"type": "t", "text": "00774-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12160745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12160745"}]}]}]}
Synonyms	ATF1, HSCR3, HFB1-GDNF, ATF2
Proteins	GDNF_HUMAN
NCBI Gene ID	2668
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GDNF has 9,446 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

GDNF 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 GDNF 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 GDNF gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of GDNF gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GDNF 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 GDNF 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 GDNF 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 GDNF gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GDNF 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 GDNF gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GDNF gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GDNF gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GDNF 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 GDNF gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GDNF gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GDNF protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GDNF protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing GDNF protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GDNF 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 GDNF 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 GDNF gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GDNF gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GDNF gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GDNF gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GDNF gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GDNF gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving GDNF gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving GDNF gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with GDNF 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 GDNF 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 GDNF 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 GDNF gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GDNF gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for GDNF protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GDNF 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 GDNF gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GDNF 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 GDNF from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GDNF gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with GDNF 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 GDNF gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.