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    GFRA1 GDNF family receptor alpha 1 [ Homo sapiens ]

    Gene ID: 2674, updated on 11-May-2012
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    Summary

    Official Symbol
    GFRA1provided by HGNC
    Official Full Name
    GDNF family receptor alpha 1provided by HGNC
    Primary source
    HGNC:4243
    See related
    Ensembl:ENSG00000151892; HPRD:03291; MIM:601496; Vega:OTTHUMG00000019097
    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
    GDNFR; RET1L; RETL1; TRNR1; GDNFRA; GFR-ALPHA-1; FLJ10561; FLJ31546; MGC23045; DKFZp313E1012; DKFZp686J0156
    Summary
    Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for Hirschsprung disease. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Feb 2009]
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    Genomic context

    Location :
    10q26.11
    Sequence :
    Chromosome: 10; NC_000010.10 (117816436..118033126, complement)
    See GFRA1 in Epigenomics, MapViewer

    Chromosome 10 - NC_000010.10Genomic Context describing neighboring genes Neighboring gene TruB pseudouridine (psi) synthase homolog 1 (E. coli) Neighboring gene attractin-like 1 Neighboring gene N-terminal asparagine amidase pseudogene Neighboring gene chromosome 10 open reading frame 96 Neighboring gene pancreatic lipase-related protein 3 Neighboring gene high mobility group box 3 pseudogene 8

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Glial cell line-derived neurotrophic factor receptor-α1 expressed in striatum in trans regulates development and injury response of dopamine neurons of the substantia nigra. Kholodilov N, et al. J Neurochem, 2011 Feb. PMID 21133924.
    2. [Multiple endocrine neoplasia: genetic aspects]. Calender A, et al. Bull Acad Natl Med, 2010 Jan. PMID 20669561.
    3. L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms. Yokoyama K, et al. Nephron Clin Pract, 2010. PMID 20424473.
    4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Rose JE, et al. Mol Med, 2010 Jul-Aug. PMID 20379614.
    5. Persephin signaling through GFRalpha1: the potential for the treatment of Parkinson's disease. Sidorova YA, et al. Mol Cell Neurosci, 2010 Jul. PMID 20350599.

    See all (54) citations in PubMed

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

    1. Post-synaptic transgenic GFRalpha1 has profound effects on the development of dopamine neurons, resulting in a 40% increase in the adult number.
      Title: Glial cell line-derived neurotrophic factor receptor-α1 expressed in striatum in trans regulates development and injury response of dopamine neurons of the substantia nigra.
    2. This study found nominally-significant evidence for interactions between GFRA1, 2 and 3 associated with schizophrenia and clozapine response, consistent with the locations of these three genes within linkage regions for schizophrenia.
      Title: Genetic association of the GDNF alpha-receptor genes with schizophrenia and clozapine response.
    3. Results identify persephin, a GDNF family member, as a novel ligand for GFRalpha1/RET receptor complex.
      Title: Persephin signaling through GFRalpha1: the potential for the treatment of Parkinson's disease.
    4. MEN2 arises from activating missense mutations in RET, causing autodimerization under certain conditions. The position of missense mutations influences medullary thyroid carcinoma aggressiveness. Review.
      Title: [Multiple endocrine neoplasia: genetic aspects].
    5. Here we report that human nigral dopaminergic neurons express GFRalpha1 and RET receptors at all ages. There was no reduction in the number of neurons expressing these receptors as a function of age.
      Title: Expression of GDNF receptors GFRalpha1 and RET is preserved in substantia nigra pars compacta of aging Asian Indians.
    6. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    7. GFR-alpha1 mRNA transcripts were detected in oocytes and GCs from all samples from fetuses, girls and adult women.
      Title: Glial cell line-derived neurotrophic factor (GDNF) and its receptors in human ovaries from fetuses, girls, and women.
    8. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Genetic association of the GDNF alpha-receptor genes with schizophrenia and clozapine response.
    9. Ape1 is a novel physiological regulator of GDNF responsiveness, and Ape1-induced GFRalpha1 expression may play important roles in pancreatic cancer progression and neuronal cell survival.
      Title: Ape1/Ref-1 induces glial cell-derived neurotropic factor (GDNF) responsiveness by upregulating GDNF receptor alpha1 expression.
    10. analysis of how GDNF.GFR alpha 1 can mediate cell adhesion and how heparin might inhibit GDNF signaling through RET
      Title: The structure of the glial cell line-derived neurotrophic factor-coreceptor complex: insights into RET signaling and heparin binding.
    Submit: New GeneRIF Correction See all (22)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P56159 P39905 GDNF    HPRD  PubMed  
    P56159 P13591 NCAM1    HPRD  PubMed  
    P56159 Q99748 NRTN    HPRD  PubMed  
    P56159 P07949 RET    HPRD  PubMed  
    BioGRID:108942 BioGRID:108936 GDNF    BioGRID  PubMed Reconstituted Complex 
    BioGRID:108942 BioGRID:110958 NRTN    BioGRID  PubMed Reconstituted Complex 
    BioGRID:108942 BioGRID:111911 RET    BioGRID  PubMed Reconstituted Complex 
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    General gene information

    Markers

    Genotypes

    Homology

    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...
    • Diurnally regulated genes with circadian orthologs, organism-specific biosystem (from WikiPathways)
      Diurnally regulated genes with circadian orthologs, organism-specific biosystemHuman genes regulated in the diurnal comparison with orthologues that display circadian regulation in mouse heart and liver (Panda 2002, Storch 2002), and SCN (Panda 2002). The 608 significantly regu...
    • 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
    glial cell-derived neurotrophic factor receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    integrin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    receptor activity NAS
    Non-traceable Author Statement
    more info
    		  
    receptor binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    axon guidance TAS
    Traceable Author Statement
    more info
    		  
    cell surface receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    glial cell-derived neurotrophic factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    nervous system development IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    anchored to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    extrinsic to membrane NAS
    Non-traceable Author Statement
    more info
    		  
    plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    GDNF family receptor alpha-1
    Names
    GDNF family receptor alpha-1
    RET ligand 1
    GDNFR-alpha-1
    GDNF receptor alpha-1
    GPI-linked anchor protein
    PI-linked cell-surface accessory protein
    TGF-beta related neurotrophic factor receptor 1
    TGF-beta-related neurotrophic factor receptor 1
    Glial cell line-derived neurotrophic factor receptor alpha
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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.

    mRNA and Protein(s)

    1. NM_001145453.1 → NP_001138925.1  GDNF family receptor alpha-1 isoform b preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an internal in-frame coding segment compared to variant 1, resulting in a shorter isoform (b).
      Source sequence(s)
      AC073588, AF038421, AK292886, AW021438
      Consensus CDS
      CCDS7593.1
      UniProtKB/Swiss-Prot
      P56159
      Related
      ENSP00000347591, OTTHUMP00000020559, ENST00000355422, OTTHUMT00000050512
      Conserved Domains (1) summary
      cl09542
      Location:238 – 332
      Blast Score: 207
      GDNF; GDNF/GAS1 domain

    2. NM_005264.4 → NP_005255.1  GDNF family receptor alpha-1 isoform a preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (a).
      Source sequence(s)
      AC012470, AC073588, AF038421, AW021438
      Consensus CDS
      CCDS44481.1
      UniProtKB/Swiss-Prot
      P56159
      Related
      ENSP00000393725, ENST00000439649
      Conserved Domains (1) summary
      cl09542
      Location:243 – 337
      Blast Score: 207
      GDNF; GDNF/GAS1 domain

    3. NM_145793.3 → NP_665736.1  GDNF family receptor alpha-1 isoform b preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an internal in-frame coding segment compared to variant 1, resulting in a shorter isoform (b).
      Source sequence(s)
      AC073588, AW021438, DA742495, U97144
      Consensus CDS
      CCDS7593.1
      UniProtKB/Swiss-Prot
      P56159
      Related
      ENSP00000358239, OTTHUMP00000020558, ENST00000369236, OTTHUMT00000050511
      Conserved Domains (1) summary
      cl09542
      Location:238 – 332
      Blast Score: 207
      GDNF; GDNF/GAS1 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

    1. NC_000010.10 Reference GRCh37.p5 Primary Assembly

      Range
      117816436..118033126, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000142.1 Alternate HuRef

      Range
      111444080..111660347, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC012470.16 (24255..84387) None
    genomic AC073588.3 (9833..166119) None
    genomic AF038420.1 AAC39693.1
    genomic AF058999.1 AAC14431.1
    genomic AL832661.1 None
    genomic CH471066.2 EAW49456.1
      EAW49457.1
      EAW49458.1
    genomic CS417511.1 CAL48763.1
    genomic CS487670.1 CAM55947.1
    mRNA AF038421.1 AAC39692.1
    mRNA AF042080.1 AAB97371.1
    mRNA AK001423.1 None
    mRNA AK056108.1 None
    mRNA AK292886.1 BAF85575.1
    mRNA AK302914.1 BAH13842.1
    mRNA AW021438.1 None
    mRNA BC014962.1 AAH14962.1
    mRNA BM675677.1 None
    mRNA BU935138.1 None
    mRNA BX648964.1 None
    mRNA DA742495.1 None
    mRNA U95847.1 AAB71811.1
    mRNA U97144.1 AAC51646.1
    other-genetic DQ892210.2 ABM83136.1
    other-genetic DQ895406.2 ABM86332.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P56159.2 GenPept UniProtKB/Swiss-Prot:P56159
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    Additional Links

    Gene LinkOut

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

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