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. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and medi... See more...

Aliases for GFRA2 Gene

Aliases for GFRA2 Gene

  • GDNF Family Receptor Alpha 2 2 3 5
  • GDNFRB 2 3 4
  • RETL2 2 3 4
  • TRNR2 2 3 4
  • TGF-Beta-Related Neurotrophic Factor Receptor 2 3 4
  • GDNF Family Receptor Alpha-2 3 4
  • Neurturin Receptor Alpha 3 4
  • GDNF Receptor Beta 3 4
  • GDNFR-Alpha-2 3 4
  • RET Ligand 2 3 4
  • GDNFR-Beta 3 4
  • NTNR-Alpha 3 4
  • NTNRA 2 3
  • Glial Cell Line Derived Neurotrophic Factor Receptor, Beta 3
  • PI-Linked Cell-Surface Accessory Protein 3
  • TRN Receptor, GPI-Anchored 3
  • GDNF Receptor Alpha-2 4
  • NRTNR-ALPHA 3
  • GFR-Alpha 2 3
  • GFR-Alpha-2 4
  • NRTNR-Alpha 4
  • GFRA2 5

External Ids for GFRA2 Gene

Previous GeneCards Identifiers for GFRA2 Gene

  • GC08M021338
  • GC08M021863
  • GC08M021559
  • GC08M021593
  • GC08M020092
  • GC08M021547

Summaries for GFRA2 Gene

Entrez Gene Summary for GFRA2 Gene

  • 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. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This encoded protein acts preferentially as a receptor for NTN compared to its other family member, GDNF family receptor alpha 1. This gene is a candidate gene for RET-associated diseases. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

GeneCards Summary for GFRA2 Gene

GFRA2 (GDNF Family Receptor Alpha 2) is a Protein Coding gene. Diseases associated with GFRA2 include Posterior Pituitary Gland Neoplasm and Atrial Tachyarrhythmia With Short Pr Interval. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include glial cell-derived neurotrophic factor receptor activity. An important paralog of this gene is GFRA1.

UniProtKB/Swiss-Prot Summary for GFRA2 Gene

  • Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.
  • [Isoform 2]: participates in NRTN-induced 'Ser-727' phosphorylation of STAT3.

Gene Wiki entry for GFRA2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GFRA2 Gene

Genomics for GFRA2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GFRA2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH08J021789 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 250.4 +23.3 23274 3.4 ZNF600 ZNF580 ZNF223 ZSCAN16 POLR2A ZNF639 ZNF341 ZEB1 KLF7 ZNF513 GFRA2 ENSG00000253200 FHIP2B CCAR2 XPO7 piR-53015 FJ601678-110
GH08J021812 Enhancer 0.8 Ensembl ENCODE 250.7 +0.4 356 2 ZNF654 POLR2A ZIC2 CTCF SMC3 YY1 NFE2 RAD21 MAZ ZNF143 GFRA2 HSALNG0063864
GH08J021857 Enhancer 1 Ensembl ENCODE 21.2 -48.5 -48544 10.2 MYC NCOR1 NFIC HES1 BHLHE40 TAL1 NFE2 MYNN ATF1 STAT5A LOC105379318 GFRA2 piR-61101-628 lnc-GFRA2-3 DOK2
GH08J021917 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 8.4 -108.0 -108019 4.9 ZNF207 ZNF654 MYC NCOR1 IKZF1 ZNF600 SIX5 ZNF580 ATF2 POLR2A XPO7 HSALNG0063869 ENSG00000253200 FHIP2B C8orf58 CCAR2 POLR3D FGF17 BMP1 BIN3
GH08J021764 Enhancer 0.8 Ensembl ENCODE 20.1 +47.0 46957 2.8 SPI1 IKZF1 ATF2 ZNF217 ZNF280D EGR2 IKZF2 NBN DPF2 RUNX3 GFRA2 FJ601678-110 piR-36393-500
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GFRA2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GFRA2

Top Transcription factor binding sites by QIAGEN in the GFRA2 gene promoter:
  • CREB
  • CUTL1
  • E47
  • GATA-2
  • MAZR
  • MZF-1
  • Olf-1
  • RP58
  • STAT3
  • Tal-1

Genomic Locations for GFRA2 Gene

Latest Assembly
chr8:21,690,398-21,812,357
(GRCh38/hg38)
Size:
121,960 bases
Orientation:
Minus strand

Previous Assembly
chr8:21,547,910-21,646,387
(GRCh37/hg19 by Entrez Gene)
Size:
98,478 bases
Orientation:
Minus strand

chr8:21,547,915-21,669,869
(GRCh37/hg19 by Ensembl)
Size:
121,955 bases
Orientation:
Minus strand

Genomic View for GFRA2 Gene

Genes around GFRA2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GFRA2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GFRA2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GFRA2 Gene

Proteins for GFRA2 Gene

  • Protein details for GFRA2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00451-GFRA2_HUMAN
    Recommended name:
    GDNF family receptor alpha-2
    Protein Accession:
    O00451
    Secondary Accessions:
    • E9PD47
    • O15316
    • O15328
    • Q58J92
    • Q6GTR9
    • Q7Z5C2

    Protein attributes for GFRA2 Gene

    Size:
    464 amino acids
    Molecular mass:
    51544 Da
    Quaternary structure:
    • Interacts with SORL1.

    Three dimensional structures from OCA and Proteopedia for GFRA2 Gene

    Alternative splice isoforms for GFRA2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GFRA2 Gene

Post-translational modifications for GFRA2 Gene

  • Glycosylation at Asn52, Asn357, and Asn413
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for GFRA2 Gene

Domains & Families for GFRA2 Gene

Gene Families for GFRA2 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for GFRA2 Gene

InterPro:
Blocks:
  • Glial cell line-derived neurotrophic factor receptor family signature
  • Glial cell line-derived neurotrophic factor receptor alpha 2 signature

Suggested Antigen Peptide Sequences for GFRA2 Gene

GenScript: Design optimal peptide antigens:
  • TGF-beta-related neurotrophic factor receptor 2 (GFRA2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O00451

UniProtKB/Swiss-Prot:

GFRA2_HUMAN :
  • Belongs to the GDNFR family.
Family:
  • Belongs to the GDNFR family.
genes like me logo Genes that share domains with GFRA2: view

Function for GFRA2 Gene

Molecular function for GFRA2 Gene

UniProtKB/Swiss-Prot Function:
Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.
UniProtKB/Swiss-Prot Function:
[Isoform 2]: participates in NRTN-induced 'Ser-727' phosphorylation of STAT3.
GENATLAS Biochemistry:
glial cell line-derived neurotrophic factor (GDNF) receptor alpha 2,47kDa,mediating the autophosphorylation of RET,abundantly expressed in adult brain,intestine,placenta,fetal brain,lung,kidney,also receptor for neurturin and TGF-beta-related neurotrophic factor

Phenotypes From GWAS Catalog for GFRA2 Gene

Gene Ontology (GO) - Molecular Function for GFRA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016167 glial cell-derived neurotrophic factor receptor activity IBA 21873635
GO:0038023 signaling receptor activity IEA,IBA 21873635
genes like me logo Genes that share ontologies with GFRA2: view
genes like me logo Genes that share phenotypes with GFRA2: view

Animal Models for GFRA2 Gene

MGI Knock Outs for GFRA2:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GFRA2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GFRA2 Gene

Localization for GFRA2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GFRA2 Gene

Cell membrane. Lipid-anchor, GPI-anchor.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GFRA2 gene
Compartment Confidence
plasma membrane 4
extracellular 2
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GFRA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IEA,TAS --
GO:0009897 external side of plasma membrane IBA 21873635
GO:0016020 membrane IEA --
GO:0019898 extrinsic component of membrane TAS 10829012
GO:0031225 anchored component of membrane IEA --
genes like me logo Genes that share ontologies with GFRA2: view

Pathways & Interactions for GFRA2 Gene

PathCards logo

SuperPathways for GFRA2 Gene

SuperPathway Contained pathways
1 RET signaling
2 GDNF-Family Ligands and Receptor Interactions
.41
.41
3 Developmental Biology
4 Cytokine Signaling in Immune system
5 Innate Immune System
genes like me logo Genes that share pathways with GFRA2: view

Pathways by source for GFRA2 Gene

1 GeneGo (Thomson Reuters) pathway for GFRA2 Gene
  • Development GDNF family signaling
1 Qiagen pathway for GFRA2 Gene
  • GDNF-Family Ligands and Receptor Interactions

SIGNOR curated interactions for GFRA2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for GFRA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway TAS 9192898
GO:0007399 nervous system development IBA 21873635
GO:0007411 axon guidance TAS --
GO:0031953 negative regulation of protein autophosphorylation IEA --
genes like me logo Genes that share ontologies with GFRA2: view

Drugs & Compounds for GFRA2 Gene

(1) Drugs for GFRA2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for GFRA2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GFRA2: view

Transcripts for GFRA2 Gene

mRNA/cDNA for GFRA2 Gene

3 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GFRA2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for GFRA2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b
SP1:
SP2: -
SP3: - -
SP4: -

Relevant External Links for GFRA2 Gene

GeneLoc Exon Structure for
GFRA2

Expression for GFRA2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GFRA2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GFRA2 Gene

This gene is overexpressed in Brain - Cortex (x6.3), Brain - Frontal Cortex (BA9) (x5.8), Brain - Anterior cingulate cortex (BA24) (x5.0), and Thyroid (x4.6).

Protein differential expression in normal tissues from HIPED for GFRA2 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (23.7), Cerebrospinal fluid (15.6), Fetal Brain (11.5), and Frontal cortex (8.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GFRA2 Gene



Protein tissue co-expression partners for GFRA2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GFRA2

SOURCE GeneReport for Unigene cluster for GFRA2 Gene:

Hs.441202

mRNA Expression by UniProt/SwissProt for GFRA2 Gene:

O00451-GFRA2_HUMAN
Tissue specificity: Isoform 1 is found in both brain and placenta.

Evidence on tissue expression from TISSUES for GFRA2 Gene

  • Nervous system(4.6)
  • Liver(4.2)
genes like me logo Genes that share expression patterns with GFRA2: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for GFRA2 Gene

Orthologs for GFRA2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for GFRA2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GFRA2 30
  • 100 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia GFRA2 29 30
  • 93.89 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia GFRA2 29 30
  • 91.52 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Gfra2 29
  • 91.24 (n)
Mouse
(Mus musculus)
Mammalia Gfra2 29 16 30
  • 90.86 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia GFRA2 30
  • 89 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia GFRA2 30
  • 84 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GFRA2 29 30
  • 76.7 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia gfra2 29
  • 60.45 (n)
Zebrafish
(Danio rerio)
Actinopterygii gfra2a 29 30
  • 68.3 (n)
OneToMany
gfra2b 30
  • 53 (a)
OneToMany
Species where no ortholog for GFRA2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for GFRA2 Gene

ENSEMBL:
Gene Tree for GFRA2 (if available)
TreeFam:
Gene Tree for GFRA2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GFRA2: view image
Alliance of Genome Resources:
Additional Orthologs for GFRA2

Paralogs for GFRA2 Gene

Paralogs for GFRA2 Gene

(2) SIMAP similar genes for GFRA2 Gene using alignment to 4 proteins:

  • GFRA2_HUMAN
  • E5RGR6_HUMAN
  • E5RJ44_HUMAN
  • J3KNF0_HUMAN
genes like me logo Genes that share paralogs with GFRA2: view

Variants for GFRA2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GFRA2 Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
rs74640671 Benign: not provided 21,693,326(-) C/T
NM_001495.5(GFRA2):c.1347G>A (p.Ser449=)
SYNONYMOUS
rs77601365 Benign: not provided 21,693,346(-) G/A
NM_001495.5(GFRA2):c.1327C>T (p.Pro443Ser)
MISSENSE
rs796065050 Drug Response: Pazopanib response 21,750,657(-) G/A
NM_001495.5(GFRA2):c.725C>T (p.Ser242Phe)
MISSENSE
rs1128397 -- p.Leu462Gln

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for GFRA2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for GFRA2 Gene

Variant ID Type Subtype PubMed ID
dgv3793n106 CNV deletion 24896259
esv25058 CNV loss 19812545
esv2675982 CNV deletion 23128226
esv2759604 CNV loss 17122850
esv3891375 CNV gain 25118596
nsv1024727 CNV gain 25217958
nsv1075122 CNV deletion 25765185
nsv1149933 CNV insertion 26484159
nsv473429 CNV novel sequence insertion 20440878
nsv474680 CNV novel sequence insertion 20440878
nsv479289 CNV novel sequence insertion 20440878
nsv480532 CNV novel sequence insertion 20440878
nsv480567 CNV novel sequence insertion 20440878

Variation tolerance for GFRA2 Gene

Residual Variation Intolerance Score: 60.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.57; 94.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GFRA2 Gene

Human Gene Mutation Database (HGMD)
GFRA2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GFRA2
Leiden Open Variation Database (LOVD)
GFRA2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GFRA2 Gene

Disorders for GFRA2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for GFRA2 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
posterior pituitary gland neoplasm
  • posterior pituitary tumor
atrial tachyarrhythmia with short pr interval
  • lown-ganong-levine syndrome
malignant granular cell myoblastoma
  • granular cell tumor, malignant
retinal degeneration
  • degeneration of retina
hirschsprung disease 1
  • hirschsprung disease, susceptibility to, 1
- elite association - COSMIC cancer census association via MalaCards
Search GFRA2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GFRA2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with GFRA2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GFRA2 Gene

Publications for GFRA2 Gene

  1. Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins. (PMID: 9177201) Sanicola M … Cate RL (Proceedings of the National Academy of Sciences of the United States of America 1997) 2 3 4 22
  2. Glial cell line-derived neurotrophic factor receptor alpha 2 (GFRA2) gene is associated with tardive dyskinesia. (PMID: 20369355) Souza RP … Wong AH (Psychopharmacology 2010) 3 22 40
  3. Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study. (PMID: 18521090) Lavedan C … Polymeropoulos MH (Molecular psychiatry 2009) 3 22 40
  4. TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. (PMID: 9182803) Baloh RH … Milbrandt J (Neuron 1997) 3 4 22
  5. Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha. (PMID: 9259272) Suvanto P … Saarma M (Human molecular genetics 1997) 3 4 22

Products for GFRA2 Gene

Sources for GFRA2 Gene