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Symbol GDNF contributors: mct - updated : 24-04-2016
HGNC name glial cell derived neurotrophic factor
HGNC id 4232
Location 5p13.2      Physical location : 37.812.778 - 37.839.782
Synonym name astrocyte-derived trophicfactor 1
Synonym symbol(s) ATF1, ATF2, HFB1-GDNF
TYPE functioning gene
STRUCTURE 24.03 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • promoter with 2 long fingers formed by pairs of anti-parallel beta strands
  • two SIX2 binding sites in the promoter that show similarity to the consensus DNA binding sequences of other homeobox proteins and harbor short palindromic sequences)
  • MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 3810 23 211 - 2004 15327782
    3 splicing 3655 20 185 - 2004 15327782
  • lacking an alternate segment in the 5' coding region compared to variant 1
  • 2 splicing 3830 - 228 - 2004 15327782
  • lacking an alternate segment in the 5' UTR
  • using a downstream start codon compared to variant 1
  • - - 3752 - 202 - 2004 15327782
    4 - 1963 - 105 - 2011 22081608
  • antisense RNA, complete sequence
  • 4 - 2944 - - - 2011 22081608
  • antisense RNA, complete sequence
  • long noncoding RNA
  • 4 - 618 - - - 2011 22081608
  • antisense RNA, complete sequence
  • long noncoding RNA
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis    Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    fluid/secretion in human milk
    at STAGE
    physiological period fetal, pregnancy
    Text developing gut, kidney, mesenchyma, developing and regenerating peripheral nerves and central nervous system
  • a cystein-knot motif at the center
  • secondary structure two helices
    conjugated GlycoP
    mono polymer homomer , dimer
    isoforms Precursor
    interspecies ortholog to rattus Gdnf
    ortholog to murine Gdnf
  • TGFB superfamily
  • GDNF subfamily
  • CATEGORY signaling growth factor
    text secreted
    basic FUNCTION
  • promoting survival and differentiation of subpopulations of central and peripheral neurons including several groups
  • stimulating Schwann cell migration via NCAM1 but independently of RET
  • playing an essential role in neural crest stem cell migration
  • enhancing survival and morphological differentiation of
  • dopaminergic neurons
  • increasing dopaminergic neurons high-affinity dopamine uptake
  • being a ligand for the product of the RET (rearranged during transfection) protooncogene
  • plays an important role in renal development, serving as a trophic factor for outgrowth of the ureteric bud and its continued arborisation
  • via activation of the MAPK pathway, is a fast-acting selective agent to reduce the motivation to consume and seek alcohol
  • constitutively produced by testicular peritubular cells and may contribute to the spermatogonial stem cell niche in man
  • promotes migration of cortical neurons in a syndecan-3-dependent manner
  • required for morphogenesis of the enteric nervous system
  • mitogenic, neurotrophic, and chemoattractive to enteric neural crest cells in the embryonic colon
  • displays a dynamic expression pattern during embryonic development that parallels the chronology of migration and differentiation of neural crest derivatives in the pancreas
  • is crucial for the development of the intrinsic innervation of the pancreas
  • CELLULAR PROCESS cell life, antiapoptosis
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development , neurogenesis
    text neurogenesis, development and maintenance of intrahippocampal circuitry and neuronal function and neuromuscular synapse
    signaling signal transduction
    a component
  • homodimer, disulfide-linked
    small molecule
  • RET ligand functioning as a dimer through prior binding to GFRA1
  • SIX4 cooperates with SIX1 in the metanephric mesenchyme to regulate the level of GDNF expression
  • interaction with NCAM1 (GDNF-induced neurite outgrowth via NCAM1 differs from NCAM1-induced neurite outgrowth by being independent of NCAM1 polysialylation)
  • promotes migration of cortical neurons in a syndecan-3-dependent manner (SDC3 may directly transduce GDNF family ligand signals or serve as a coreceptor, presenting GDNF family ligand to the signaling receptor RET)
  • increased SPHK1 transcription, leading to the production and secretion of S1P
  • restores human blood-nerve barrier function via RET tyrosine kinase-mediated cytoskeletal reorganization
  • NRG1 inhibited the GDNF-induced neuronal differentiation and GDNF negatively regulated NRG1-signaling by down-regulating the expression of its receptor, ERBB2
  • SPIN1 directly enhances expression of GDNF, an activator of the RET signaling pathway, in cooperation with the transcription factor MAZ
  • JAG1 Regulates GDNF Expression in Sertoli cells
  • cell & other
  • paracrine regulation of spermatogonal self-reserval and differentiation
    Other regulated by NR4A1 (FSH-induced NR4A1 regulates the expression of GDNF in Sertoli cells to stimulate the proliferation of A spermatogonia)
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in postmortem middle temporal gyrus (MTG) of Alzheimer disease (AD)
  • susceptibility to Hirschsprung disease and to phaeochromocytoma
  • to renal aplasia
  • to medullary sponge kidney disease
  • Variant & Polymorphism other
  • polymorphisms increasing the risk of renal aplasia
  • sequence variations in patients with medullary sponge kidney disease
  • Candidate gene candidate modifier in neurofibromatosis (NF1) enteric phenotype
    Therapy target
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    DNSP-11 exhibits potent neurotrophic actions analogous to GDNF, making it a viable candidate for a PD therapeutic