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    GFRA4 GDNF family receptor alpha 4 [ Homo sapiens (human) ]

    Gene ID: 64096, updated on 10-Dec-2024

    Summary

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    Official Symbol
    GFRA4provided by HGNC
    Official Full Name
    GDNF family receptor alpha 4provided by HGNC
    Primary source
    HGNC:HGNC:13821
    See related
    Ensembl:ENSG00000125861 MIM:618679; AllianceGenome:HGNC:13821
    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
    Summary
    The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for persephin, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for RET-associated diseases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
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    Genomic context

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    See GFRA4 in Genome Data Viewer
    Location:
    20p13
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (3659248..3663399, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (3690188..3694336, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (3639895..3644046, complement)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17480 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12621 Neighboring gene TCEAL9 pseudogene 1 Neighboring gene attractin Neighboring gene splicing factor 3a, subunit 3 pseudogene 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:3601641-3601840 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17481 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12622 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr20:3647557-3648086 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:3651223-3651828 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:3657784-3658386 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:3658990-3659591 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:3662082-3662975 Neighboring gene ADAM metallopeptidase domain 33 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:3678505-3679004 Neighboring gene Sharpr-MPRA regulatory region 3812 Neighboring gene sialic acid binding Ig like lectin 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Demethylation of GFRA4 Promotes Cell Proliferation and Invasion in Hirschsprung Disease. Wang G, et al. DNA Cell Biol, 2018 Apr. PMID 29634418
    2. hGFRalpha-4: a new member of the GDNF receptor family and a candidate for NBIA. Zhou B, et al. Pediatr Neurol, 2001 Aug. PMID 11551746
    3. MiR-195-5p inhibits proliferation and invasion of nerve cells in Hirschsprung disease by targeting GFRA4. Wang G, et al. Mol Cell Biochem, 2021 May. PMID 33515383
    4. Downregulation of microRNA-483-5p Promotes Cell Proliferation and Invasion by Targeting GFRA4 in Hirschsprung's Disease. Wang G, et al. DNA Cell Biol, 2017 Nov. PMID 29090971
    5. Human glial cell line-derived neurotrophic factor receptor alpha 4 is the receptor for persephin and is predominantly expressed in normal and malignant thyroid medullary cells. Lindahl M, et al. J Biol Chem, 2001 Mar 23. PMID 11116144

    See all (12) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MiR-195-5p inhibits proliferation and invasion of nerve cells in Hirschsprung disease by targeting GFRA4.
      Title: MiR-195-5p inhibits proliferation and invasion of nerve cells in Hirschsprung disease by targeting GFRA4.
    2. Results support that aberrant CpG hypermethylation at least partly accounts for GFRA4 silencing in HSCR, which impairs its protective role in enteric nervous system.
      Title: Demethylation of GFRA4 Promotes Cell Proliferation and Invasion in Hirschsprung Disease.
    3. High GFRA4 expression is associated with Hirschsprung's Disease.
      Title: Downregulation of microRNA-483-5p Promotes Cell Proliferation and Invasion by Targeting GFRA4 in Hirschsprung's Disease.
    4. Observational study of gene-disease association. (HuGE Navigator)
      Title: Investigation of germline GFRA4 mutations and evaluation of the involvement of GFRA1, GFRA2, GFRA3, and GFRA4 sequence variants in Hirschsprung disease.
    5. GDNF/GFRalpha1 is crucial for efficient signal transduction to recruit Ret protein into lipid rafts.
      Title: PSPN/GFRalpha4 has a significantly weaker capacity than GDNF/GFRalpha1 to recruit RET to rafts, but promotes neuronal survival and neurite outgrowth.
    Submit: New GeneRIF Correction

    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

    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 glial cell-derived neurotrophic factor receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glial cell-derived neurotrophic factor receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in glial cell-derived neurotrophic factor receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of ossification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nervous system development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ossification IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    GDNF family receptor alpha-4
    Names
    GDNF receptor alpha-4
    GDNFR-alpha-4
    GFR receptor alpha 4
    GFR-alpha-4
    persephin receptor

    NCBI Reference Sequences (RefSeq)

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    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_022139.4 → NP_071422.1  GDNF family receptor alpha-4 isoform a precursor

      See identical proteins and their annotated locations for NP_071422.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the predominant isoform (a).
      Source sequence(s)
      AF253318, AL356755
      Consensus CDS
      CCDS13055.1
      UniProtKB/Swiss-Prot
      Q9GZZ7
      Related
      ENSP00000290417.2, ENST00000290417.7
      Conserved Domains (1) summary
      pfam02351
      Location:117 → 211
      GDNF; GDNF/GAS1 domain

    2. NM_145762.3 → NP_665705.1  GDNF family receptor alpha-4 isoform b precursor

      See identical proteins and their annotated locations for NP_665705.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes additional segments in the coding region compared to variant 1, that cause internal frameshift. The resulting isoform (b) contains additional aa in the middle of the protein, but has the same N- and C-terminal ends as isoform a.
      Source sequence(s)
      AJ291674, AL356755
      Consensus CDS
      CCDS13056.1
      UniProtKB/Swiss-Prot
      Q5JT74, Q9GZZ7, Q9H191, Q9H192
      Related
      ENSP00000313423.3, ENST00000319242.8
      Conserved Domains (1) summary
      pfam02351
      Location:202 → 241
      GDNF; GDNF/GAS1 domain

    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_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      3659248..3663399 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005260793.2 → XP_005260850.1  GDNF family receptor alpha-4 isoform X1

      See identical proteins and their annotated locations for XP_005260850.1

      UniProtKB/Swiss-Prot
      Q9GZZ7
      Related
      ENSP00000435801.1, ENST00000477160.1
      Conserved Domains (2) summary
      smart00907
      Location:117 → 170
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:26 → 105
      GDNF; GDNF/GAS1 domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      3690188..3694336 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054323832.1 → XP_054179807.1  GDNF family receptor alpha-4 isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_145763.1: Suppressed sequence

      Description
      NM_145763.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9GZZ7.2 GenPept UniProtKB/Swiss-Prot:Q9GZZ7

    Gene LinkOut

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

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