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

Gene ID: 2674, updated on 13-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (116056925..116274705, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (116951015..117168680, complement)
105.20220307 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. Deficiency of GFRα1 promotes hepatocellular carcinoma progression but enhances oxaliplatin-mediated anti-tumor efficacy. Zhu H, et al. Pharmacol Res, 2021 Oct. PMID 34391932
  2. Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer. Dong Z, et al. PLoS Genet, 2020 Nov. PMID 33175846, Free PMC Article
  3. Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis. Arora V, et al. J Am Soc Nephrol, 2021 Jan. PMID 33020172, Free PMC Article
  4. 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
  5. 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

See all (91) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis.
    Title: Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis.
  7. 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.
  8. 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.
  9. 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.
  10. Low expression of EZH2 in the colon tissue of children with Hirschsprung's disease may be one of the causes of inadequate expression of GFRalpha1 and onset of Hirschsprung's disease
    Title: [Effect of enhancer of zeste homolog 2 on the expression of glial cell line-derived neurotrophic factor family receptor α-1 in the colon tissue of children with Hirschsprung's disease].
Submit: New GeneRIF Correction See all GeneRIFs (48)

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)

Genotypes

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 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
  
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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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_2023_10

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

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