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

    Gene ID: 2668, updated on 9-Dec-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
    mouse all
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    Genomic context

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    See GDNF in Genome Data Viewer
    Location:
    5p13.2
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (37812677..37840041, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (38061739..38089107, complement)
    RS_2024_09 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. Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma. Xiong Y, et al. Oncotarget, 2017 Apr 11. PMID 28212546, Free PMC Article
    2. Increased levels of plasma glial-derived neurotrophic factor in children with attention deficit hyperactivity disorder. Shim SH, et al. Nord J Psychiatry, 2015. PMID 25753832
    3. Increased levels of glial cell-derived neurotrophic factor in CSF of infants with SMA. Chiaretti A, et al. Pediatr Neurol, 2009 Sep. PMID 19664536
    4. Glial cell-line derived neurotrophic factor (GDNF) concentrations in cerebrospinal fluid and serum of patients with early Alzheimer's disease and normal controls. Straten G, et al. J Alzheimers Dis, 2009. PMID 19584438
    5. GDNF gene is associated with tourette syndrome in a family study. Huertas-Fernández I, et al. Mov Disord, 2015 Jul. PMID 26096985, Free PMC Article

    See all (256) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Glial-Cell-Line-Derived Neurotrophic Factor Promotes Glioblastoma Cell Migration and Invasion via the SMAD2/3-SERPINE1-Signaling Axis.
      Title: Glial-Cell-Line-Derived Neurotrophic Factor Promotes Glioblastoma Cell Migration and Invasion via the SMAD2/3-SERPINE1-Signaling Axis.
    2. GDNF/GFRA1 signaling contributes to chemo- and radioresistance in glioblastoma.
      Title: GDNF/GFRA1 signaling contributes to chemo- and radioresistance in glioblastoma.
    3. MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism.
      Title: MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. Finding an Optimal Level of GDNF Overexpression: Insights from Dopamine Cycling.
      Title: Finding an Optimal Level of GDNF Overexpression: Insights from Dopamine Cycling.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (183)

    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
    		Compare labs

    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)

    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
    		  
    is_active_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    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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    NEW Try the new Transcript table

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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