GDNF glial cell derived neurotrophic factor [Homo sapiens] - Gene

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Summary

Official Symbol: GDNFprovided by HGNC
Official Full Name: glial cell derived neurotrophic factorprovided by HGNC
Primary source: HGNC:4232
See related: Ensembl:ENSG00000168621; HPRD:02906; MIM:600837; Vega:OTTHUMG00000090809
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: ATF1; ATF2; HSCR3; HFB1-GDNF
Summary: This gene encodes a highly conserved neurotrophic factor. The recombinant form of this protein 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. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene may be associated with Hirschsprung disease. [provided by RefSeq, Jun 2010]

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Genomic context

Location :: 5p13.1-p12

Sequence :: Chromosome: 5; NC_000005.9 (37812779..37839782, complement)

See GDNF in Epigenomics, MapViewer

Chromosome 5 - NC_000005.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

This study provides evidence for a direct, receptor-mediated effect of GDNF on osteoblasts highlighting a novel role for GDNF in bone physiology.
Title: Glial cell line-derived neurotrophic factor influences proliferation of osteoblastic cells.
Identification of novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease
Title: Identification of novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease.
results showed that in TGW cells, GDNF increased SPHK1 transcription, leading to the production and secretion of S1P
Title: Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription.
Findings, together with the detection of sequence variants in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some cases in combination with RET or GDNF mutations, provide evidence to consider them as susceptibility genes for HSCR.
Title: Expression of PROKR1 and PROKR2 in human enteric neural precursor cells and identification of sequence variants suggest a role in HSCR.
overexpression of SorLA could enhance the regulated secretion of the GDNF prodomain-GFP fusion protein, suggesting that the prodomain of GDNF is responsible for its regulated secretion.
Title: Sorting protein-related receptor SorLA controls regulated secretion of glial cell line-derived neurotrophic factor.
patients Methamphetamine dependent were divided in two groups having of multi-drug vs MAP-only users, we detected significant association between the two groups and tagging SNP rs2910704. GDNF likely related to severity of MAP use in Japanese population
Title: Association analysis of the GDNF gene with methamphetamine use disorder in a Japanese population.
S100B protein, BDNF, and GDNF are present in all samples of human milk, and they may be responsible for the long term effects of breast feeding.
Title: S100B protein, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in human milk.
These results suggest that genomic alteration of RET or GDNF is not a major mechanism leading to renal agenesis and other severe kidney development defects.
Title: RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects.
findings suggest that late-onset depression (LOD) patients in acute phase have extensive impairments of cognitive function, and higher plasma GDNF might be involved in the pathogenesis of LOD, which may be associated with the cognitive dysfunction in LOD.
Title: Association study between plasma GDNF and cognitive function in late-onset depression.
FSH-induced Nur77 regulates the expression of GDNF in Sertoli cells to stimulate the proliferation of A spermatogonia in vitro.
Title: FSH acts on the proliferation of type A spermatogonia via Nur77 that increases GDNF expression in the Sertoli cells.

Submit: New GeneRIF Correction See all (73)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Central hypoventilation syndrome

MIM: 209880

Genome-wide association study of recurrent early-onset major depressive disorder.

Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract. The aganglionic segment includes the distal rectum and a variable length of contiguous proximal intestine. In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (short-segment disease); in 15%-20%, aganglionosis extends proximal to the sigmoid colon (long-segment disease); in about 5%, aganglionosis affects the entire large intestine (total colonic aganglionosis). Rarely, the aganglionosis extends into the small bowel or even more proximally to encompass the entire bowel (total intestinal aganglionosis). HSCR is considered a neurocristopathy, a disorder of cells and tissues derived from the neural crest, and may occur as an isolated finding or as part of a multisystem disorder. Affected infants frequently present in the first two months of life with symptoms of impaired intestinal motility such as failure to pass meconium within the first 48 hours of life, constipation, emesis, abdominal pain or distention, and occasionally diarrhea. However, because the initial diagnosis of HSCR may be delayed until late childhood or adulthood, HSCR should be considered in anyone with lifelong severe constipation. Individuals with HSCR are at risk for enterocolitis and/or potentially lethal intestinal perforation.

Diagnosis Testing

The diagnosis of HSCR requires histopathologic demonstration of absence of enteric ganglion cells in the distal rectum. Suction biopsies of rectal mucosa and submucosa are the preferred diagnostic test in most centers because they can be performed safely without general anesthesia. Syndromes associated with HSCR are diagnosed by clinical findings, cytogenetic analysis, or in some cases, by specific molecular or biochemical tests. Isolated HSCR is a multigene disorder that has been associated with mutations in at least six different genes.

Genetic Counseling

Recurrence risk depends on the underlying cause.

Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
P39905	P39905	GDNF	HPRD	PubMed
P39905	P56159	GFRA1	HPRD	PubMed
P39905	O00451	GFRA2	HPRD	PubMed
P39905	P13591	NCAM1	HPRD	PubMed
P39905	P07949	RET	HPRD	PubMed
BioGRID:108936	BioGRID:108942	GFRA1	BioGRID	PubMed	Reconstituted Complex
BioGRID:108936	BioGRID:108943	GFRA2	BioGRID	PubMed	Reconstituted Complex

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General gene information

Markers

D11S2921 (e-PCR)
- UniSTS:152074

Gdnf (e-PCR), detects polymorphism
- UniSTS:234030

NoName (e-PCR)
- UniSTS:481584

RH70036 (e-PCR)
- UniSTS:56907

Gdnf (e-PCR), detects polymorphism
- UniSTS:143192

SHGC-148195 (e-PCR)
- UniSTS:176253

Gdnf (e-PCR), detects polymorphism
- UniSTS:497281

GDNF_3150 (e-PCR)
- UniSTS:462211

D5S2021 (e-PCR)
- UniSTS:78753

GDNF (e-PCR)
- UniSTS:505778

Genotypes

See GDNF SNP Geneview Report
See GDNF SNP Genotype Report
See GDNF SNP Variation Viewer Report

Homology

Homologs of the GDNF gene: The GDNF gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Axon guidance, organism-specific biosystem (from REACTOME)
Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
NCAM signaling for neurite out-growth, organism-specific biosystem (from REACTOME)
NCAM signaling for neurite out-growth, organism-specific biosystemThe neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the n...
NCAM1 interactions, organism-specific biosystem (from REACTOME)
NCAM1 interactions, organism-specific biosystemThe neural cell adhesion molecule, NCAM1 is generally considered as a cell adhesion mediator, but it is also considered to be a signal transducing receptor molecule. NCAM1 is involved in multiple cis...
Signaling events regulated by Ret tyrosine kinase, organism-specific biosystem (from Pathway Interaction Database)
Signaling events regulated by Ret tyrosine kinase, organism-specific biosystem
Signaling events regulated by Ret tyrosine kinase

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
growth factor activity	NAS Non-traceable Author Statement more info
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
receptor binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
adult locomotory behavior	TAS Traceable Author Statement more info	PubMed
anti-apoptosis	IEA Inferred from Electronic Annotation more info
axon guidance	TAS Traceable Author Statement more info
branching involved in ureteric bud morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
enteric nervous system development	ISS Inferred from Sequence or Structural Similarity more info
mRNA stabilization	IDA Inferred from Direct Assay more info	PubMed
metanephros development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IDA Inferred from Direct Assay more info	PubMed
negative regulation of neuron apoptosis	IDA Inferred from Direct Assay more info	PubMed
nervous system development	TAS Traceable Author Statement more info	PubMed
neural crest cell migration	IDA Inferred from Direct Assay more info	PubMed
neuron projection development	IDA Inferred from Direct Assay more info	PubMed
organ induction	IEA Inferred from Electronic Annotation more info
peristalsis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of branching involved in ureteric bud morphogenesis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of dopamine secretion	TAS Traceable Author Statement more info	PubMed
positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of monooxygenase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of ureteric bud formation	IDA Inferred from Direct Assay more info	PubMed
postganglionic parasympathetic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
postsynaptic membrane organization	IEA Inferred from Electronic Annotation more info
regulation of dopamine uptake	IDA Inferred from Direct Assay more info	PubMed
regulation of morphogenesis of a branching structure	ISS Inferred from Sequence or Structural Similarity more info
signal transduction	TAS Traceable Author Statement more info	PubMed
sympathetic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
ureteric bud development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
extracellular region	IDA Inferred from Direct Assay more info	PubMed

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General protein information

Preferred Names: glial cell line-derived neurotrophic factor

Names: glial cell line-derived neurotrophic factor; ATF; astrocyte-derived trophic factor

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NCBI Reference Sequences (RefSeq)

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

NG_011675.2 RefSeqGene

Range

5001..32004

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000514.3 → NP_000505.1 glial cell line-derived neurotrophic factor isoform 1 preproprotein

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

P39905

Related

ENSP00000317145, OTTHUMP00000116024, ENST00000326524, OTTHUMT00000207606

Conserved Domains (1) summary

cl02510
Location:118 – 211
Blast Score: 187

TGF_beta; Transforming growth factor beta like domain
NM_001190468.1 → NP_001177397.1 glial cell line-derived neurotrophic factor isoform 3 preproprotein

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, OTTHUMP00000221305, ENST00000427982, OTTHUMT00000367337

Conserved Domains (1) summary

cl02510
Location:135 – 228
Blast Score: 190

TGF_beta; Transforming growth factor beta like domain
NM_001190469.1 → NP_001177398.1 glial cell line-derived neurotrophic factor isoform 4 preproprotein

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, OTTHUMP00000116025, ENST00000381826, OTTHUMT00000207607

Conserved Domains (1) summary

cl02510
Location:109 – 202
Blast Score: 188

TGF_beta; Transforming growth factor beta like domain
NM_199231.2 → NP_954701.1 glial cell line-derived neurotrophic factor isoform 2 preproprotein

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/Swiss-Prot

P39905

Related

ENSP00000339703, ENST00000344622

Conserved Domains (1) summary

cl02510
Location:92 – 185
Blast Score: 185

TGF_beta; Transforming growth factor beta like domain

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000005.9 Reference GRCh37.p5 Primary Assembly

Range

37812779..37839782, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000137.1 Alternate HuRef

Range

37765313..37792316, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC008869.5 (108960..135962)	None
genomic	AF053749.1	None
genomic	AF063586.1	AAC98782.1
genomic	AJ001896.1	CAA05074.1
genomic	CH471119.1	EAW55963.1
		EAW55964.1
genomic	HI949612.1	CBY79817.1
genomic	L19063.1	AAA67910.1
mRNA	AF053748.1	AAD43139.1
mRNA	AJ001897.1	CAA05075.1
mRNA	AJ001898.1	CAA05076.1
mRNA	AJ001899.1	CAA05077.1
mRNA	AJ001900.1	CAA05078.1
mRNA	AY052832.1	AAL11017.1
mRNA	BC008580.1	AAH08580.1
mRNA	BC069119.1	AAH69119.1
mRNA	BC069369.1	AAH69369.1
mRNA	BC128108.1	AAI28109.1
mRNA	BC128109.1	AAI28110.1
mRNA	CR541923.1	CAG46721.1
mRNA	DQ235474.1	None