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GDNF glial cell derived neurotrophic factor [ Homo sapiens (human) ]

Gene ID: 2668, updated on 13-Apr-2024

Summary

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Official Symbol
GDNFprovided by HGNC
Official Full Name
glial cell derived neurotrophic factorprovided by HGNC
Primary source
HGNC:HGNC:4232
See related
Ensembl:ENSG00000168621 MIM:600837; AllianceGenome:HGNC:4232
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ATF; ATF1; ATF2; HSCR3; HFB1-GDNF
Summary
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]
Expression
Broad expression in placenta (RPKM 1.7), ovary (RPKM 1.5) and 18 other tissues See more
Orthologs
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Genomic context

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Location:
5p13.2
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (37812677..37840041, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (38061739..38089107, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (37812779..37840143, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene WD repeat domain 70 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:37630447-37630947 Neighboring gene RNA, U6 small nuclear 1190, pseudogene Neighboring gene Sharpr-MPRA regulatory region 3878 Neighboring gene Sharpr-MPRA regulatory region 6618 Neighboring gene Sharpr-MPRA regulatory region 9268 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:37724134-37725333 Neighboring gene RNA, U6 small nuclear 484, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr5:37756428-37756676 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:37836250-37837188 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22490 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:37839067-37840004 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:37847590-37848789 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22492 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22493 Neighboring gene GDNF antisense RNA 1 Neighboring gene NANOG hESC enhancer GRCh37_chr5:37938025-37938604 Neighboring gene long intergenic non-protein coding RNA 2117 Neighboring gene long intergenic non-protein coding RNA 2110

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The role of glial cell line-derived neurotrophic factor isoforms in human glial tumors. Revishchin AV, et al. Zh Vopr Neirokhir Im N N Burdenko, 2022. PMID 36534631
  2. GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1. Yu Z, et al. Int J Oncol, 2022 Sep. PMID 35894143, Free PMC Article
  3. Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B. Yang G, et al. Can J Gastroenterol Hepatol, 2022. PMID 35855954, Free PMC Article
  4. Transposon-mediated glial cell line-derived neurotrophic factor overexpression in human adipose tissue-derived mesenchymal stromal cells: A potential approach for neuroregenerative medicine? Rasińska J, et al. J Tissue Eng Regen Med, 2022 Jun. PMID 35278347
  5. Decreased Expression of Glial-Derived Neurotrophic Factor Receptors in Glaucomatous Human Retinas. Akurathi A, et al. Curr Eye Res, 2022 Apr. PMID 34738835

See all (245) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease.
    Title: Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease.
  2. Plasma GDNF levels in spinal dysraphism and its relation with neurological impairment in children: A point of care study.
    Title: Plasma GDNF levels in spinal dysraphism and its relation with neurological impairment in children: A point of care study.
  3. The significance of glial cell line-derived neurotrophic factor analysis in Progressive Supranuclear Palsy.
    Title: The significance of glial cell line-derived neurotrophic factor analysis in Progressive Supranuclear Palsy.
  4. Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate.
    Title: Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate.
  5. Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration.
    Title: Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration.
  6. Finding an Optimal Level of GDNF Overexpression: Insights from Dopamine Cycling.
    Title: Finding an Optimal Level of GDNF Overexpression: Insights from Dopamine Cycling.
  7. High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer.
    Title: High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer.
  8. GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1.
    Title: GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1.
  9. Overexpression of microRNA-211 in Functional Dyspepsia via Downregulation of the Glial Cell Line-Derived Neurotrophic Factor (GDNF) by Increasing Phosphorylation of p38 MAPK Pathway.
    Title: Overexpression of microRNA-211 in Functional Dyspepsia via Downregulation of the Glial Cell Line-Derived Neurotrophic Factor (GDNF) by Increasing Phosphorylation of p38 MAPK Pathway.
  10. [The role of glial cell line-derived neurotrophic factor isoforms in human glial tumors].
    Title: The role of glial cell line-derived neurotrophic factor isoforms in human glial tumors.
Submit: New GeneRIF Correction See all GeneRIFs (180)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hirschsprung disease, susceptibility to, 3
MedGen: C3150974 OMIM: 613711 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association study of recurrent early-onset major depressive disorder.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables chemoattractant activity involved in axon guidance TAS
Traceable Author Statement
more info
 PubMed 
enables glial cell-derived neurotrophic factor receptor binding IEA
Inferred from Electronic Annotation
more info
  
enables growth factor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables growth factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables receptor tyrosine kinase binding IEA
Inferred from Electronic Annotation
more info
  
enables signaling receptor binding TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in adult locomotory behavior TAS
Traceable Author Statement
more info
 PubMed 
involved_in branching involved in ureteric bud morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in chemoattraction of axon IEA
Inferred from Electronic Annotation
more info
  
involved_in commissural neuron axon guidance ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in dorsal spinal cord development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in embryonic organ development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in enteric nervous system development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in glial cell-derived neurotrophic factor receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mRNA stabilization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mesenchymal to epithelial transition involved in metanephros morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in metanephros development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of neuron apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of neuron apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in nervous system development TAS
Traceable Author Statement
more info
 PubMed 
acts_upstream_of_or_within neural crest cell migration IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within neuron projection development IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in neuron projection development TAS
Traceable Author Statement
more info
 PubMed 
involved_in organ induction IEA
Inferred from Electronic Annotation
more info
  
involved_in peripheral nervous system development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in peristalsis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of branching involved in ureteric bud morphogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of branching involved in ureteric bud morphogenesis IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within positive regulation of cell differentiation IGI
Inferred from Genetic Interaction
more info
 PubMed 
acts_upstream_of_or_within positive regulation of cell population proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of dopamine secretion TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of monooxygenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of ureteric bud formation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in postganglionic parasympathetic fiber development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in postsynaptic membrane organization IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of dopamine uptake involved in synaptic transmission IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within regulation of gene expression IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in regulation of morphogenesis of a branching structure ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of semaphorin-plexin signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of stem cell differentiation TAS
Traceable Author Statement
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in sympathetic nervous system development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in ureteric bud formation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular region IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
glial cell line-derived neurotrophic factor
Names
astrocyte-derived trophic factor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011675.2 RefSeqGene

    Range
    4640..32004
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000514.4 → NP_000505.1  glial cell line-derived neurotrophic factor isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_000505.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR, represents use of an alternate promoter, and uses a downstream start codon, compared to variant 3. The resulting isoform (1) has a shorter N-terminus, compared to isoform 3.
    Source sequence(s)
    AC008869, AF053748, AY052832
    Consensus CDS
    CCDS3922.1
    UniProtKB/Swiss-Prot
    B7WPK7, O95448, O95449, O95986, P39905, Q6FH33, Q96L44, Q9UD32, Q9UD33, Q9UMV2, Q9UP67, Q9UP97
    UniProtKB/TrEMBL
    A0A0S2Z3V2
    Related
    ENSP00000317145.2, ENST00000326524.7
    Conserved Domains (1) summary
    cd19380
    Location:115 → 210
    TGF_beta_GDNF; transforming growth factor beta (TGF-beta) like domain found in glial cell line-derived neurotrophic factor (GDNF) and similar proteins

  2. NM_001190468.1 → NP_001177397.1  glial cell line-derived neurotrophic factor isoform 3 precursor

    See identical proteins and their annotated locations for NP_001177397.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
    Source sequence(s)
    AC008869, AJ001897
    Consensus CDS
    CCDS54845.1
    UniProtKB/Swiss-Prot
    P39905
    Related
    ENSP00000409007.1, ENST00000427982.5
    Conserved Domains (1) summary
    cd19380
    Location:132 → 227
    TGF_beta_GDNF; transforming growth factor beta (TGF-beta) like domain found in glial cell line-derived neurotrophic factor (GDNF) and similar proteins

  3. NM_001190469.1 → NP_001177398.1  glial cell line-derived neurotrophic factor isoform 4 precursor

    See identical proteins and their annotated locations for NP_001177398.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice site in the coding region, compared to variant 3. The resulting isoform (4) lacks an internal segment, compared to isoform 3.
    Source sequence(s)
    AC008869, AJ001898
    Consensus CDS
    CCDS54846.1
    UniProtKB/Swiss-Prot
    P39905
    Related
    ENSP00000371248.4, ENST00000381826.8
    Conserved Domains (1) summary
    cd19380
    Location:106 → 201
    TGF_beta_GDNF; transforming growth factor beta (TGF-beta) like domain found in glial cell line-derived neurotrophic factor (GDNF) and similar proteins

  4. NM_001278098.1 → NP_001265027.1  glial cell line-derived neurotrophic factor isoform 5

    See identical proteins and their annotated locations for NP_001265027.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) has a unique internal exon, which causes translation initiation at a downstream AUG, compared to variant 1. The encoded isoform (5) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AC008869, AJ001900, DQ235474
    Consensus CDS
    CCDS75237.1
    UniProtKB/Swiss-Prot
    P39905
    Related
    ENSP00000478722.1, ENST00000620847.1
    Conserved Domains (1) summary
    pfam00019
    Location:66 → 158
    TGF_beta; Transforming growth factor beta like domain

  5. NM_199231.2 → NP_954701.1  glial cell line-derived neurotrophic factor isoform 2 precursor

    See identical proteins and their annotated locations for NP_954701.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, represents use of an alternate promoter, uses a downstream start codon, and uses an alternate in-frame splice site in the coding region, compared to variant 3. The resulting isoform (2) has a shorter N-terminus and lacks an internal segment, compared to isoform 3.
    Source sequence(s)
    AC008869, AJ001899, AY052832
    Consensus CDS
    CCDS3923.1
    UniProtKB/TrEMBL
    A0A0S2Z3T2
    Related
    ENSP00000339703.4, ENST00000344622.8
    Conserved Domains (1) summary
    cd19380
    Location:89 → 184
    TGF_beta_GDNF; transforming growth factor beta (TGF-beta) like domain found in glial cell line-derived neurotrophic factor (GDNF) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    37812677..37840041 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017009337.3 → XP_016864826.1  glial cell line-derived neurotrophic factor isoform X1

    UniProtKB/TrEMBL
    A0A0S2Z3T2
    Related
    ENSP00000425928.1, ENST00000515058.5
    Conserved Domains (1) summary
    cd19380
    Location:89 → 184
    TGF_beta_GDNF; transforming growth factor beta (TGF-beta) like domain found in glial cell line-derived neurotrophic factor (GDNF) and similar proteins

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    38061739..38089107 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352364.1 → XP_054208339.1  glial cell line-derived neurotrophic factor isoform X1

    UniProtKB/TrEMBL
    A0A0S2Z3T2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_199234.1: Suppressed sequence

    Description
    NM_199234.1: This RefSeq was permanently suppressed because it represents a poorly supported variant with non-consensus splice sites.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P39905.1 GenPept UniProtKB/Swiss-Prot:P39905

Gene LinkOut

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