Human Gene GFRA4 (ENST00000290417.7) from GENCODE V44
  Description: Homo sapiens GDNF family receptor alpha 4 (GFRA4), transcript variant 1, mRNA. (from RefSeq NM_022139)
RefSeq Summary (NM_022139): 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].
Gencode Transcript: ENST00000290417.7
Gencode Gene: ENSG00000125861.16
Transcript (Including UTRs)
   Position: hg38 chr20:3,659,248-3,663,399 Size: 4,152 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg38 chr20:3,659,909-3,663,399 Size: 3,491 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsPrimersCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr20:3,659,248-3,663,399)mRNA (may differ from genome)Protein (269 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=GDNF family receptor alpha-4; Short=GDNF receptor alpha-4; Short=GDNFR-alpha-4; Short=GFR-alpha-4; AltName: Full=Persephin receptor; Flags: Precursor;
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.
SUBCELLULAR LOCATION: Isoform GFRalpha4a: Cell membrane; Lipid- anchor, GPI-anchor.
SUBCELLULAR LOCATION: Isoform GFRalpha4b: Cell membrane; Lipid- anchor, GPI-anchor.
SUBCELLULAR LOCATION: Isoform GFRalpha4c: Secreted.
TISSUE SPECIFICITY: Predominantly expressed in the adult thyroid gland. Low levels also found in fetal adrenal and thyroid glands.
SIMILARITY: Belongs to the GDNFR family.

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 0.34 RPKM in Testis
Total median expression: 1.65 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -229.80661-0.348 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016017 - GDNF/GAS1
IPR003438 - GDNF_rcpt

Pfam Domains:
PF02351 - GDNF/GAS1 domain

ModBase Predicted Comparative 3D Structure on Q9GZZ7
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0016167 glial cell-derived neurotrophic factor receptor activity
GO:0038023 signaling receptor activity

Biological Process:
GO:0000165 MAPK cascade
GO:0007411 axon guidance
GO:0030279 negative regulation of ossification
GO:0035860 glial cell-derived neurotrophic factor receptor signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0031225 anchored component of membrane

-  Descriptions from all associated GenBank mRNAs
  AF253318 - Homo sapiens GFR receptor alpha 4 protein (GFRA4) mRNA, complete cds.
JD422863 - Sequence 403887 from Patent EP1572962.
JD282132 - Sequence 263156 from Patent EP1572962.
JD295495 - Sequence 276519 from Patent EP1572962.
JD188193 - Sequence 169217 from Patent EP1572962.
JD514010 - Sequence 495034 from Patent EP1572962.
JD063108 - Sequence 44132 from Patent EP1572962.
JD102900 - Sequence 83924 from Patent EP1572962.
JD060771 - Sequence 41795 from Patent EP1572962.
JD439071 - Sequence 420095 from Patent EP1572962.
JD392851 - Sequence 373875 from Patent EP1572962.
JD516418 - Sequence 497442 from Patent EP1572962.
AJ291673 - Homo sapiens mRNA for GDNF family receptor alpha 4, GPI anchored isoform (GFRA4 gene).
AJ291674 - Homo sapiens mRNA for putative GDNF family receptor alpha 4, GPI anchored isoform b (GFRA4 gene).
BC172271 - Synthetic construct Homo sapiens clone IMAGE:100068965, MGC:198976 GDNF family receptor alpha 4 (GFRA4) mRNA, encodes complete protein.
BC172567 - Synthetic construct Homo sapiens clone IMAGE:100069261, MGC:199272 GDNF family receptor alpha 4 (GFRA4) mRNA, encodes complete protein.
JD318086 - Sequence 299110 from Patent EP1572962.
JD409216 - Sequence 390240 from Patent EP1572962.
JD073591 - Sequence 54615 from Patent EP1572962.
JD071393 - Sequence 52417 from Patent EP1572962.
JD404500 - Sequence 385524 from Patent EP1572962.
AJ291675 - Homo sapiens mRNA for putative GDNF family receptor alpha 4, secreted isoform c (GFRA4 gene).

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9GZZ7 (Reactome details) participates in the following event(s):

R-HSA-8871227 RET binds GFRA4
R-HSA-8853801 PSPN binds RET:GFRA4
R-HSA-375149 Interaction of NCAM1 with GFRalpha-1
R-HSA-375144 Interaction of NCAM1:GFRalpha-1 with GDNF
R-HSA-8853762 RET dimerizes
R-HSA-8854908 PKA phosphorylates RET:GDNF:GFRA dimer
R-HSA-8853792 RET tyrosine phosphorylation
R-HSA-8853737 2x p-5Y-RET:GDNF:GFRA complexes bind SHC1
R-HSA-8853753 2x p-5Y-RET:GDNF:GFRA complexes bind GRB7,10
R-HSA-8853755 2x p-5Y-RET:GDNF:GFRA complexes bind PLCgamma1
R-HSA-8854899 2x p-5Y-RET:GDNF:GFRA complexes bind GRB2-1:SOS1
R-HSA-8855564 2x p-5Y-RET:GDNF:GFRA complexes bind FRS2
R-HSA-8855617 2x p-5Y-RET:GDNF:GFRA complexes binds DOK1,DOK2,DOK4,DOK5,DOK6
R-HSA-8855747 2x p-5Y-RET:GDNF:GFRA complexes bind SRC1, RAP1GAP
R-HSA-8855915 2x p-5Y-RET:GDNF:GFRA complexes bind RET interactors
R-HSA-8853734 2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 binds GRB2-1:SOS1
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-8855508 p-5Y-GAB in RET-GRB2-GAB complexes binds PTPN11
R-HSA-8853659 RET signaling
R-HSA-419037 NCAM1 interactions
R-HSA-422475 Axon guidance
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-1266738 Developmental Biology
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000290417.1, ENST00000290417.2, ENST00000290417.3, ENST00000290417.4, ENST00000290417.5, ENST00000290417.6, GFRA4_HUMAN, NM_022139, Q5JT74, Q9GZZ7, Q9H191, Q9H192, uc002win.1, uc002win.2, uc002win.3, uc002win.4
UCSC ID: ENST00000290417.7
RefSeq Accession: NM_022139
Protein: Q9GZZ7 (aka GFRA4_HUMAN or GFR4_HUMAN)
CCDS: CCDS13055.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.