Seroatlas · Human Serome Atlas

GFRA2

GDNF family receptor alpha-2

Also known as: GDNFRB, GFRA2_HUMAN, NTNRA, RETL2, TRNR2

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
O00451
Gene
GFRA2
Ensembl
ENSG00000168546
Chromosome
8
Canonical length
464 aa
Protein class
Predicted intracellular proteins
Subcellular location
Vesicles,Plasma membrane
Secretome location
Intracellular and membrane

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

464 residues, UniProt reviewed canonical sequence.

>O00451|GFRA2
     1  MILANVFCLF FFLDETLRSL ASPSSLQGPE LHGWRPPVDC VRANELCAAE SNCSSRYRTL
    61  RQCLAGRDRN TMLANKECQA ALEVLQESPL YDCRCKRGMK KELQCLQIYW SIHLGLTEGE
   121  EFYEASPYEP VTSRLSDIFR LASIFSGTGA DPVVSAKSNH CLDAAKACNL NDNCKKLRSS
   181  YISICNREIS PTERCNRRKC HKALRQFFDR VPSEYTYRML FCSCQDQACA ERRRQTILPS
   241  CSYEDKEKPN CLDLRGVCRT DHLCRSRLAD FHANCRASYQ TVTSCPADNY QACLGSYAGM
   301  IGFDMTPNYV DSSPTGIVVS PWCSCRGSGN MEEECEKFLR DFTENPCLRN AIQAFGNGTD
   361  VNVSPKGPSF QATQAPRVEK TPSLPDDLSD STSLGTSVIT TCTSVQEQGL KANNSKELSM
   421  CFTELTTNII PGSNKVIKPN SGPSRARPSA ALTVLSVLML KLAL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GFRA2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.41
Highest tissue expression
9 nTPM

Expression across tissuesHPA

Tissue

  • testis: 9 nTPM
  • thyroid gland: 8.2 nTPM
  • spleen: 7 nTPM
  • placenta: 6.7 nTPM
  • cerebral cortex: 4.8 nTPM
  • cervix: 2.4 nTPM

Single-cell type

  • retinal horizontal cells: 453 nCPM
  • late spermatids: 422 nCPM
  • early spermatids: 130 nCPM
  • kupffer cells: 92 nCPM
  • adrenal medulla cells: 75 nCPM
  • epididymal efferent duct absorptive cells: 71 nCPM

Immune cell

  • intermediate monocyte: 9.3 nTPM
  • myeloid DC: 2.5 nTPM
  • classical monocyte: 1.9 nTPM
  • non-classical monocyte: 1.3 nTPM
  • total PBMC: 0.9 nTPM
  • eosinophil: 0.8 nTPM

Brain region

  • cerebral cortex: 27 nTPM
  • hypothalamus: 21 nTPM
  • basal ganglia: 17 nTPM
  • midbrain: 16 nTPM
  • white matter: 15 nTPM
  • hippocampal formation: 15 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.69
gnomAD pLI
0.1
gnomAD missense Z
0.14
DepMap mean gene effect
0.03
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of GFRA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads GFRA2 as an antibody target. Whether an autoantibody or antibody against GFRA2 could matter depends on whether native GFRA2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

GFRA2 is annotated at the cell surface, where native GFRA2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label GFRA2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/GFRA2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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