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    GFRA1 GDNF family receptor alpha 1 [ Homo sapiens (human) ]

    Gene ID: 2674, updated on 10-Dec-2024

    Summary

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    Official Symbol
    GFRA1provided by HGNC
    Official Full Name
    GDNF family receptor alpha 1provided by HGNC
    Primary source
    HGNC:HGNC:4243
    See related
    Ensembl:ENSG00000151892 MIM:601496; AllianceGenome:HGNC:4243
    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; RHDA4; TRNR1; GDNFRA; GFRalpha-1; GFR-ALPHA-1; GDNFR-alpha-1
    Summary
    This gene encodes a member of the glial cell line-derived neurotrophic factor receptor (GDNFR) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature receptor. 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. This receptor 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. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
    Expression
    Ubiquitous expression in fat (RPKM 5.5), brain (RPKM 4.5) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GFRA1 in Genome Data Viewer
    Location:
    10q25.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (116056925..116274705, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (116951015..117168680, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (117816436..118034217, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene attractin like 1 Neighboring gene uncharacterized LOC105378497 Neighboring gene N-terminal asparagine amidase pseudogene 1 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr10:117734419-117735117 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr10:117735118-117735816 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:117755064-117755832 Neighboring gene Sharpr-MPRA regulatory region 9774 Neighboring gene small nucleolar RNA, C/D box 158 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:118032883-118033720 Neighboring gene uncharacterized LOC107984273 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2854 Neighboring gene coiled-coil domain containing 172 Neighboring gene small nuclear ribonucleoprotein polypeptide G pseudogene 6

    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. Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment. Gattei V, et al. Blood, 1997 Apr 15. PMID 9108413
    2. Deficiency of GDNF Receptor GFRα1 in Alzheimer's Neurons Results in Neuronal Death. Konishi Y, et al. J Neurosci, 2014 Sep 24. PMID 25253858, Free PMC Article
    3. Assignment of the GDNF family receptor alpha-1 (GFRA1) to human chromosome band 10q26 by in situ hybridization. Gorodinsky A, et al. Cytogenet Cell Genet, 1997. PMID 9465905
    4. Mutational analysis of the GDNF/RET-GDNFR alpha signaling complex in a kindred with vesicoureteral reflux. Shefelbine SE, et al. Hum Genet, 1998 Apr. PMID 9600247
    5. Impact of GFRA1 gene reactivation by DNA demethylation on prognosis of patients with metastatic colon cancer. Ma WR, et al. World J Gastroenterol, 2020 Jan 14. PMID 31988584, Free PMC Article

    See all (95) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. GDNF/GFRA1 signaling contributes to chemo- and radioresistance in glioblastoma.
      Title: GDNF/GFRA1 signaling contributes to chemo- and radioresistance in glioblastoma.
    2. The Role of Promyelocytic Leukemia Zinc Finger (PLZF) and Glial-Derived Neurotrophic Factor Family Receptor Alpha 1 (GFRalpha1) in the Cryopreservation of Spermatogonia Stem Cells.
      Title: The Role of Promyelocytic Leukemia Zinc Finger (PLZF) and Glial-Derived Neurotrophic Factor Family Receptor Alpha 1 (GFRα1) in the Cryopreservation of Spermatogonia Stem Cells.
    3. LMX1B Activated Circular RNA GFRA1 Modulates the Tumorigenic Properties and Immune Escape of Prostate Cancer.
      Title: LMX1B Activated Circular RNA GFRA1 Modulates the Tumorigenic Properties and Immune Escape of Prostate Cancer.
    4. CircGFRA1 facilitates the malignant progression of HER-2-positive breast cancer via acting as a sponge of miR-1228 and enhancing AIFM2 expression.
      Title: CircGFRA1 facilitates the malignant progression of HER-2-positive breast cancer via acting as a sponge of miR-1228 and enhancing AIFM2 expression.
    5. Deficiency of GFRalpha1 promotes hepatocellular carcinoma progression but enhances oxaliplatin-mediated anti-tumor efficacy.
      Title: Deficiency of GFRα1 promotes hepatocellular carcinoma progression but enhances oxaliplatin-mediated anti-tumor efficacy.
    6. LncRNA LINC00210 regulated radiosensitivity of osteosarcoma cells via miR-342-3p/GFRA1 axis.
      Title: LncRNA LINC00210 regulated radiosensitivity of osteosarcoma cells via miR-342-3p/GFRA1 axis.
    7. Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis.
      Title: Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis.
    8. Generation of an Oncolytic Herpes Simplex Viral Vector Completely Retargeted to the GDNF Receptor GFRalpha1 for Specific Infection of Breast Cancer Cells.
      Title: Generation of an Oncolytic Herpes Simplex Viral Vector Completely Retargeted to the GDNF Receptor GFRα1 for Specific Infection of Breast Cancer Cells.
    9. Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer.
      Title: Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer.
    10. GFRA1 expression is frequently reactivated by DNA demethylation in colon cancer (CC) tissues and is significantly associated with a poor prognosis in patients with CC, especially those with metastatic CC. GFRA1 can promote the proliferation/growth of CC cells, probably by the activation of AKT and ERK pathways.
      Title: Impact of GFRA1 gene reactivation by DNA demethylation on prognosis of patients with metastatic colon cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (49)

    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

    Associated conditions

    Description Tests
    Renal hypodysplasia/aplasia 4
    MedGen: C5676993 OMIM: 619887 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide meta-analysis identifies new susceptibility loci for migraine.
    EBI GWAS Catalog
    Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif downregulates the expression of GDNF family receptor alpha 1 (GFRA1) in Vif-expression T cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Clone Names

    • FLJ10561, FLJ31546, MGC23045, DKFZp313E1012, DKFZp686J0156

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables glial cell-derived neurotrophic factor receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables integrin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables neurotrophin receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables signaling receptor binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell surface receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in glial cell-derived neurotrophic factor receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in kidney development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in male gonad development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nervous system development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in neuron projection development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neurotrophin signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of peptidyl-tyrosine phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extrinsic component of membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in multivesicular body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of plasma membrane protein complex IEA
    Inferred from Electronic Annotation
    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-1
    Names
    GDNF receptor alpha 1d
    GDNF receptor alpha 1e
    GPI-linked anchor protein
    Glial cell line-derived neurotrophic factor receptor alpha
    PI-linked cell-surface accessory protein
    RET ligand 1
    TGF-beta-related neurotrophic factor receptor 1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_050620.1 RefSeqGene

      Range
      5440..221721
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001145453.4 → NP_001138925.1  GDNF family receptor alpha-1 isoform b precursor

      See identical proteins and their annotated locations for NP_001138925.1

      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). The encoded isoform (b) may undergo proteolytic processing similar to isoform a. Variants 2-4 and 8-11 all encode the same isoform (b).
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS7593.1
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Related
      ENSP00000507970.1, ENST00000682743.1
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    2. NM_001348096.3 → NP_001335025.1  GDNF family receptor alpha-1 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), as well as variants 2 and 3, encodes isoform b. Variants 2-4 and 8-11 all encode the same isoform (b).
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS7593.1
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Related
      ENSP00000393725.3, ENST00000439649.8
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    3. NM_001348098.4 → NP_001335027.1  GDNF family receptor alpha-1 isoform a preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6), as well as variant 1, encodes isoform a.
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS44481.1
      UniProtKB/Swiss-Prot
      A8KA21, O15507, O43912, P56159
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Conserved Domains (2) summary
      smart00907
      Location:29 → 111
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:243 → 337
      GDNF; GDNF/GAS1 domain

    4. NM_001348099.3 → NP_001335028.1  GDNF family receptor alpha-1 isoform c

      Status: REVIEWED

      Source sequence(s)
      AC012470, AC073588
      UniProtKB/TrEMBL
      B7Z856
      Conserved Domains (1) summary
      pfam02351
      Location:122 → 216
      GDNF; GDNF/GAS1 domain

    5. NM_001382556.2 → NP_001369485.1  GDNF family receptor alpha-1 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8), as well as variants 2-4 and 9-11, encodes isoform b.
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS7593.1
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    6. NM_001382557.2 → NP_001369486.1  GDNF family receptor alpha-1 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9), as well as variants 2-4, 8, 10, and 11, encodes isoform b.
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS7593.1
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    7. NM_001382558.2 → NP_001369487.1  GDNF family receptor alpha-1 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10), as well as variants 2-4, 8, 9, and 11, encodes isoform b.
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS7593.1
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Related
      ENSP00000506818.1, ENST00000684105.1
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    8. NM_001382559.2 → NP_001369488.1  GDNF family receptor alpha-1 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (11), as well as variants 2-4 and 8-10, encodes isoform b.
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS7593.1
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    9. NM_001382560.2 → NP_001369489.1  GDNF family receptor alpha-1 isoform d precursor

      Status: REVIEWED

      Source sequence(s)
      AC012470, AC073588
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    10. NM_001382561.2 → NP_001369490.1  GDNF family receptor alpha-1 isoform e precursor

      Status: REVIEWED

      Source sequence(s)
      AC012470, AC073588
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      GDNF; GDNF/GAS1 domain

    11. NM_005264.8 → NP_005255.1  GDNF family receptor alpha-1 isoform a preproprotein

      See identical proteins and their annotated locations for NP_005255.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 6 both encode the same isoform (a).
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS44481.1
      UniProtKB/Swiss-Prot
      A8KA21, O15507, O43912, P56159
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Related
      ENSP00000347591.6, ENST00000355422.11
      Conserved Domains (2) summary
      smart00907
      Location:29 → 111
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:243 → 337
      GDNF; GDNF/GAS1 domain

    12. NM_145793.7 → NP_665736.1  GDNF family receptor alpha-1 isoform b precursor

      See identical proteins and their annotated locations for NP_665736.1

      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). The encoded isoform (b) may undergo proteolytic processing similar to isoform a. Variants 2-4 and 8-11 all encode the same isoform (b).
      Source sequence(s)
      AC012470, AC073588
      Consensus CDS
      CCDS7593.1
      UniProtKB/TrEMBL
      A0A7R7YCG5
      Related
      ENSP00000358239.1, ENST00000369236.5
      Conserved Domains (2) summary
      smart00907
      Location:149 → 228
      GDNF; GDNF/GAS1 domain
      pfam02351
      Location:238 → 332
      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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      116056925..116274705 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      116951015..117168680 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P56159.2 GenPept UniProtKB/Swiss-Prot:P56159

    Gene LinkOut

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

    Other Literature Sources
    Chemical Information
    Molecular Biology Databases
    Research Materials
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