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

Summary

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

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_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis.
Title: Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis.
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.
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.
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.
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 EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AFMA338XB5 (e-PCR)
- UniSTS:11777

WI-11643 (e-PCR)
- UniSTS:2314

RH46367 (e-PCR)
- UniSTS:79635

RH123055 (e-PCR)
- UniSTS:135448

SHGC-60298 (e-PCR)
- UniSTS:51500

D10S1330E (e-PCR)
- UniSTS:58157

RH44743 (e-PCR)
- UniSTS:11568

D10S0108 (e-PCR)
- UniSTS:240962

D10S0404 (e-PCR)
- UniSTS:240963

D10S0499 (e-PCR)
- UniSTS:240964

D10S2383 (e-PCR)
- UniSTS:21065

D10S2181 (e-PCR)
- UniSTS:21066

G31142 (e-PCR)
- UniSTS:42826

RH123893 (e-PCR)
- UniSTS:136268

RH92804 (e-PCR)
- UniSTS:88237

D10S1748 (e-PCR)
- UniSTS:69821

D10S1471 (e-PCR)
- UniSTS:42715

SHGC-133025 (e-PCR)
- UniSTS:170980

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 more info	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

NG_050620.1 RefSeqGene

Range

5440..221721

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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
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
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
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
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
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
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
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