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 g... See more...

Aliases for GFRA4 Gene

Aliases for GFRA4 Gene

  • GDNF Family Receptor Alpha 4 2 3 5
  • Persephin Receptor 2 3 4
  • GDNF Family Receptor Alpha-4 3 4
  • GDNF Receptor Alpha-4 3 4
  • GDNFR-Alpha-4 3 4
  • GFR-Alpha-4 3 4
  • GFR Receptor Alpha 4 3

External Ids for GFRA4 Gene

Previous GeneCards Identifiers for GFRA4 Gene

  • GC20M003627
  • GC20M003634

Summaries for GFRA4 Gene

Entrez Gene Summary for GFRA4 Gene

  • 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]

GeneCards Summary for GFRA4 Gene

GFRA4 (GDNF Family Receptor Alpha 4) is a Protein Coding gene. Diseases associated with GFRA4 include Spinocerebellar Ataxia 23 and Hirschsprung Disease 1. 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 GFRA2.

UniProtKB/Swiss-Prot Summary for GFRA4 Gene

  • Receptor for persephin. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. May be important in C-cell development and, in the postnatal development of the adrenal medulla.

Additional gene information for GFRA4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GFRA4 Gene

Genomics for GFRA4 Gene

GeneHancer (GH) Regulatory Elements for GFRA4 Gene

Promoters and enhancers for GFRA4 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
GH20J003652 Enhancer 0.8 Ensembl ENCODE 5.4 +10.2 10199 3.6 MYC NCOR1 MAX SPI1 EHMT2 TAL1 TCF12 RCOR1 ZNF384 ATF2 SIGLEC1 HSPA12B ATRN GFRA4 piR-36768
GH20J003612 Enhancer 0.7 Ensembl CraniofacialAtlas 4.7 +49.5 49499 2.2 ZNF341 CTCF ZFHX2 ZNF664 BHLHE40 EGR2 ETV6 SCRT2 CEBPB ATRN GFRA4 piR-36768 piR-31534-391
GH20J003629 Enhancer 0.3 Ensembl 4.9 +33.3 33298 1 JUND SIGLEC1 HSPA12B GFRA4 piR-36768 piR-31534-391 ATRN
GH20J003658 Enhancer 1.1 Ensembl ENCODE 0.7 +4.3 4298 1.4 POLR2G SP1 SIX5 EP300 KDM6A ZBTB25 RCOR1 ZBTB7A SKI TEAD1 SIGLEC1 HSPA12B VPS16 GFRA4 piR-36768
GH20J003666 Enhancer 1 Ensembl ENCODE 0.7 -3.1 -3102 2.2 ZNF300 RBAK ZNF662 CTBP1 HINFP RBM25 ZNF491 ZNF195 NFIC ZNF592 ENSG00000229539 MRPS26 ATRN GFRA4 lnc-GFRA4-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GFRA4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GFRA4

Top Transcription factor binding sites by QIAGEN in the GFRA4 gene promoter:
  • ATF
  • C/EBPalpha
  • CHOP-10
  • E47
  • Egr-4
  • LCR-F1
  • NRSF form 1
  • NRSF form 2
  • STAT3
  • STAT5A

Genomic Locations for GFRA4 Gene

Genomic Locations for GFRA4 Gene
chr20:3,659,292-3,663,399
(GRCh38/hg38)
Size:
4,108 bases
Orientation:
Minus strand
chr20:3,639,939-3,644,046
(GRCh37/hg19)
Size:
4,108 bases
Orientation:
Minus strand

Genomic View for GFRA4 Gene

Genes around GFRA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GFRA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GFRA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GFRA4 Gene

Proteins for GFRA4 Gene

  • Protein details for GFRA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9GZZ7-GFRA4_HUMAN
    Recommended name:
    GDNF family receptor alpha-4
    Protein Accession:
    Q9GZZ7
    Secondary Accessions:
    • Q5JT74
    • Q9H191
    • Q9H192

    Protein attributes for GFRA4 Gene

    Size:
    299 amino acids
    Molecular mass:
    31670 Da
    Quaternary structure:
    • Interacts with SORL1.

    Alternative splice isoforms for GFRA4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GFRA4 Gene

Post-translational modifications for GFRA4 Gene

  • Glycosylation at Asn208

Other Protein References for GFRA4 Gene

No data available for DME Specific Peptides for GFRA4 Gene

Domains & Families for GFRA4 Gene

Gene Families for GFRA4 Gene

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

Protein Domains for GFRA4 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GFRA4 Gene

GenScript: Design optimal peptide antigens:
  • Persephin receptor (GFRA4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9GZZ7

UniProtKB/Swiss-Prot:

GFRA4_HUMAN :
  • Belongs to the GDNFR family.
Family:
  • Belongs to the GDNFR family.
genes like me logo Genes that share domains with GFRA4: view

Function for GFRA4 Gene

Molecular function for GFRA4 Gene

UniProtKB/Swiss-Prot Function:
Receptor for persephin. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. May be important in C-cell development and, in the postnatal development of the adrenal medulla.

Phenotypes From GWAS Catalog for GFRA4 Gene

Gene Ontology (GO) - Molecular Function for GFRA4 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 --
genes like me logo Genes that share ontologies with GFRA4: view
genes like me logo Genes that share phenotypes with GFRA4: view

Animal Models for GFRA4 Gene

MGI Knock Outs for GFRA4:

Animal Model Products

  • Taconic Biosciences Mouse Models for GFRA4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GFRA4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for GFRA4 Gene

Localization for GFRA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GFRA4 Gene

[Isoform GFRalpha4a]: Cell membrane; Lipid-anchor, GPI-anchor.
[Isoform GFRalpha4b]: Cell membrane; Lipid-anchor, GPI-anchor.
[Isoform GFRalpha4c]: Secreted.

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 GFRA4 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 1

Gene Ontology (GO) - Cellular Components for GFRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IEA --
GO:0005886 plasma membrane TAS --
GO:0009897 external side of plasma membrane IBA 21873635
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with GFRA4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GFRA4 Gene

Pathways & Interactions for GFRA4 Gene

PathCards logo

SuperPathways for GFRA4 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 GFRA4: view

Pathways by source for GFRA4 Gene

1 GeneGo (Thomson Reuters) pathway for GFRA4 Gene
  • Development GDNF family signaling
1 Qiagen pathway for GFRA4 Gene
  • GDNF-Family Ligands and Receptor Interactions

SIGNOR curated interactions for GFRA4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for GFRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0007399 nervous system development IBA 21873635
GO:0007411 axon guidance TAS --
GO:0030279 negative regulation of ossification IEA --
GO:0035860 glial cell-derived neurotrophic factor receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with GFRA4: view

Drugs & Compounds for GFRA4 Gene

No Compound Related Data Available

Transcripts for GFRA4 Gene

mRNA/cDNA for GFRA4 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GFRA4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GFRA4 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5
SP1: -
SP2:
SP3:

Relevant External Links for GFRA4 Gene

GeneLoc Exon Structure for
GFRA4

Expression for GFRA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GFRA4 Gene

mRNA differential expression in normal tissues according to GTEx for GFRA4 Gene

This gene is overexpressed in Thyroid (x9.6), Brain - Amygdala (x7.7), Brain - Hippocampus (x7.5), and Testis (x4.9).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GFRA4

SOURCE GeneReport for Unigene cluster for GFRA4 Gene:

Hs.302025

mRNA Expression by UniProt/SwissProt for GFRA4 Gene:

Q9GZZ7-GFRA4_HUMAN
Tissue specificity: Predominantly expressed in the adult thyroid gland. Low levels also found in fetal adrenal and thyroid glands.

Evidence on tissue expression from TISSUES for GFRA4 Gene

  • Thyroid gland(4)
genes like me logo Genes that share expression patterns with GFRA4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for GFRA4 Gene

Orthologs for GFRA4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for GFRA4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GFRA4 31 30
  • 97.04 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GFRA4 31 30
  • 86.88 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GFRA4 31 30
  • 83.55 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Gfra4 17 31 30
  • 80 (n)
rat
(Rattus norvegicus)
Mammalia Gfra4 30
  • 78.02 (n)
oppossum
(Monodelphis domestica)
Mammalia GFRA4 31
  • 34 (a)
OneToOne
chicken
(Gallus gallus)
Aves GFRA4 31
  • 27 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GFRA4 31
  • 26 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii BX247898.1 31
  • 26 (a)
OneToMany
gfra4 31
  • 25 (a)
OneToMany
Species where no ortholog for GFRA4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for GFRA4 Gene

ENSEMBL:
Gene Tree for GFRA4 (if available)
TreeFam:
Gene Tree for GFRA4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GFRA4: view image

Paralogs for GFRA4 Gene

Paralogs for GFRA4 Gene

genes like me logo Genes that share paralogs with GFRA4: view

Variants for GFRA4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GFRA4 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
692314 Uncertain Significance: Fetal akinesia sequence; Arthrogryposis multiplex congenita 3,661,092(-) C/G MISSENSE_VARIANT
736462 Likely Benign: not provided 3,660,517(-) G/C INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for GFRA4 Gene

Structural Variations from Database of Genomic Variants (DGV) for GFRA4 Gene

Variant ID Type Subtype PubMed ID
nsv520565 CNV loss 19592680

Variation tolerance for GFRA4 Gene

Gene Damage Index Score: 2.20; 39.74% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GFRA4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GFRA4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GFRA4 Gene

Disorders for GFRA4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for GFRA4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
spinocerebellar ataxia 23
  • sca23
hirschsprung disease 1
  • hirschsprung disease, susceptibility to, 1
- elite association - COSMIC cancer census association via MalaCards
Search GFRA4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GFRA4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GFRA4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GFRA4 Gene

Publications for GFRA4 Gene

  1. 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. (PMID: 11116144) Lindahl M … Saarma M (The Journal of biological chemistry 2001) 3 4 23 54
  2. PSPN/GFRalpha4 has a significantly weaker capacity than GDNF/GFRalpha1 to recruit RET to rafts, but promotes neuronal survival and neurite outgrowth. (PMID: 15225646) Yang J … Saarma M (FEBS letters 2004) 2 3 54
  3. Investigation of germline GFRA4 mutations and evaluation of the involvement of GFRA1, GFRA2, GFRA3, and GFRA4 sequence variants in Hirschsprung disease. (PMID: 12624147) Borrego S … Eng C (Journal of medical genetics 2003) 3 41 54
  4. The DNA sequence and comparative analysis of human chromosome 20. (PMID: 11780052) Deloukas P … Rogers J (Nature 2001) 3 4 54
  5. Mammalian GFRalpha -4, a divergent member of the GFRalpha family of coreceptors for glial cell line-derived neurotrophic factor family ligands, is a receptor for the neurotrophic factor persephin. (PMID: 10958791) Masure S … Gordon RD (The Journal of biological chemistry 2000) 2 3 54

Products for GFRA4 Gene

Sources for GFRA4 Gene