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

Gene ID: 64096, updated on 11-Apr-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (3659248..3663399, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (3690188..3694336, complement)
105.20220307 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 uncharacterized LOC105372508 Neighboring gene uncharacterized LOC105372509 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17479 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17480 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12621 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 12622 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12623 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: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 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)

Genotypes

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
  
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_2023_10

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

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