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    GFRA2 GDNF family receptor alpha 2 [ Homo sapiens ]

    Gene ID: 2675, updated on 11-May-2012
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    Summary

    Official Symbol
    GFRA2provided by HGNC
    Official Full Name
    GDNF family receptor alpha 2provided by HGNC
    Primary source
    HGNC:4244
    See related
    Ensembl:ENSG00000168546; HPRD:11801; MIM:601956; Vega:OTTHUMG00000163897
    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
    NTNRA; RETL2; TRNR2; GDNFRB; NRTNR-ALPHA
    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 encoded protein acts preferentially as a receptor for NTN compared to its other family member, GDNF family receptor alpha 1. This gene is a candidate gene for RET-associated diseases. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
    Annotation information
    Annotation category: suggests misassembly
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    Genomic context

    Location :
    8p21.3
    Sequence :
    Chromosome: 8; NC_000008.10 (21549530..21646346, complement)
    See GFRA2 in Epigenomics, MapViewer

    Chromosome 8 - NC_000008.10Genomic Context describing neighboring genes Neighboring gene transmembrane protein 97 pseudogene 2 Neighboring gene uncharacterized LOC286114 Neighboring gene olfactory receptor, family 6, subfamily R, member 2 pseudogene Neighboring gene docking protein 2, 56kDa

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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. Cyclic AMP signalling through PKA but not Epac is essential for neurturin-induced biphasic ERK1/2 activation and neurite outgrowths through GFRα2 isoforms. Wan G, et al. Cell Signal, 2011 Nov. PMID 21723942.
    2. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. Flachsbart F, et al. Mutat Res, 2010 Dec 10. PMID 20800603.
    3. Glial cell line-derived neurotrophic factor receptor alpha 2 (GFRA2) gene is associated with tardive dyskinesia. Souza RP, et al. Psychopharmacology (Berl), 2010 Jun. PMID 20369355.
    4. Genetic association of the GDNF alpha-receptor genes with schizophrenia and clozapine response. Souza RP, et al. J Psychiatr Res, 2010 Aug. PMID 20116071.
    5. Genetic evidence for a role of IL33 in nasal polyposis. Buysschaert ID, et al. Allergy, 2010 May. PMID 19860791.

    See all (22) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

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

    1. Cyclic AMP signalling through PKA but not Epac is essential for neurturin-induced biphasic ERK1/2 activation and neurite outgrowths through GFRalpha2 isoforms.
      Title: Cyclic AMP signalling through PKA but not Epac is essential for neurturin-induced biphasic ERK1/2 activation and neurite outgrowths through GFRα2 isoforms.
    2. GFRA2 genetic variants, and age, may play a role in susceptibility to tardive dyskinesia.
      Title: Glial cell line-derived neurotrophic factor receptor alpha 2 (GFRA2) gene is associated with tardive dyskinesia.
    3. 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.
    4. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Glial cell line-derived neurotrophic factor receptor alpha 2 (GFRA2) gene is associated with tardive dyskinesia.
    5. Clinical trial of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Applicability of a genetic signature for enhanced iloperidone efficacy in the treatment of schizophrenia.
    6. Genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
    8. GFRalpha-2 were observed within sensory and motor nuclei of cranial nerves, dorsal column nuclei, olivary nuclear complex, reticular formation, pontine nuclei, locus caeruleus, raphe nuclei, substantia nigra, and quadrigeminal plate.
      Title: Tissue distribution of Ret, GFRalpha-1, GFRalpha-2 and GFRalpha-3 receptors in the human brainstem at fetal, neonatal and adult age.
    9. Both GFR alpha2a and GFR alpha2c, but not GFR alpha2b, promote neurite outgrowth in transfected Neuro2A cells.
      Title: Glial cell line-derived neurotrophic factor and neurturin inhibit neurite outgrowth and activate RhoA through GFR alpha 2b, an alternatively spliced isoform of GFR alpha 2.
    Submit: New GeneRIF Correction
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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
    O00451 P39905 GDNF    HPRD  PubMed  
    O00451 Q99748 NRTN    HPRD  PubMed  
    BioGRID:108943 BioGRID:108936 GDNF    BioGRID  PubMed Reconstituted Complex 
    BioGRID:108943 BioGRID:110958 NRTN    BioGRID  PubMed Reconstituted Complex 
    BioGRID:108943 BioGRID:111700 PTEN    BioGRID  PubMed Affinity Capture-MS 
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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...
    • 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...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    glial cell-derived neurotrophic factor receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    glial cell-derived neurotrophic factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    transmembrane receptor protein tyrosine kinase signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    anchored to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    extrinsic to membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    GDNF family receptor alpha-2
    Names
    GDNF family receptor alpha-2
    GDNFR-beta
    NTNR-alpha
    GFR-alpha 2
    RET ligand 2
    GDNFR-alpha-2
    GDNF receptor beta
    neurturin receptor alpha
    TRN receptor, GPI-anchored
    PI-linked cell-surface accessory protein
    TGF-beta-related neurotrophic factor receptor 2
    glial cell line derived neurotrophic factor receptor, beta
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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

    1. NG_029215.1 RefSeqGene

      Range
      5001..101817
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001165038.1 → NP_001158510.1  GDNF family receptor alpha-2 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The resulting isoform (b) lacks an internal segment near the N-terminus, compared to isoform a. It is not known if this variant is targeted to the cell membrane.
      Source sequence(s)
      AY941828, BC041688
      Consensus CDS
      CCDS55208.1
      UniProtKB/TrEMBL
      E9PD47
      UniProtKB/Swiss-Prot
      O00451
      UniProtKB/TrEMBL
      Q58J92
      Related
      ENSP00000383592, ENST00000400782
      Conserved Domains (1) summary
      cl09542
      Location:146 – 242
      Blast Score: 199
      GDNF; GDNF/GAS1 domain

    2. NM_001165039.1 → NP_001158511.1  GDNF family receptor alpha-2 isoform c precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two alternate in-frame exons in the 5' coding region, compared to variant 1. The resulting isoform (c) lacks an internal segment near the N-terminus, compared to isoform a. It is not known if this variant is targeted to the cell membrane.
      Source sequence(s)
      AY326396, BC041688
      Consensus CDS
      CCDS55207.1
      UniProtKB/Swiss-Prot
      O00451
      Related
      ENSP00000429206, OTTHUMP00000225305, ENST00000518077, OTTHUMT00000376255
      Conserved Domains (1) summary
      cl09542
      Location:118 – 214
      Blast Score: 195
      GDNF; GDNF/GAS1 domain

    3. NM_001495.4 → NP_001486.4  GDNF family receptor alpha-2 isoform a preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      BC041688
      Consensus CDS
      CCDS47816.1
      UniProtKB/Swiss-Prot
      O00451
      Related
      ENSP00000428518, OTTHUMP00000225304, ENST00000524240, OTTHUMT00000376254
      Conserved Domains (1) summary
      cl09542
      Location:251 – 347
      Blast Score: 195
      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_000008.10 Reference GRCh37.p5 Primary Assembly

      Range
      21549530..21646346, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000140.1 Alternate HuRef

      Range
      20092831..20150935, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC105186.14 (44245..103169) None
    genomic AC129925.12 (54185..68047) None
    genomic AP008236.2 (421..6154) None
    genomic CH471080.2 EAW63742.1
    genomic CS487672.1 CAM55948.1
    mRNA AF002700.1 AAC52036.1
    mRNA AK299623.1 BAG61551.1
    mRNA AY326396.1 AAP88378.1
    mRNA AY941828.1 AAX46325.1
    mRNA BC041688.1 AAH41688.1
    mRNA U93703.1 AAB61922.1
    mRNA U97145.1 AAC51647.1
    other-genetic JF432396.1 ADZ15613.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00451.2 GenPept UniProtKB/Swiss-Prot:O00451
    Q58J92 GenPept UniProtKB/TrEMBL:Q58J92
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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.

    Chemical Information
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