Seroatlas · Human Serome Atlas

RET

Proto-oncogene tyrosine-protein kinase receptor Ret

Also known as: CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1, PTC, RET_HUMAN, RET51

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

Protein identityUniProt · HPA

UniProt accession
P07949
Gene
RET
Ensembl
ENSG00000165731
Chromosome
10
Canonical length
1114 aa
Protein class
Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Golgi apparatus,Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]

Canonical amino-acid sequenceUniProt

1114 residues, UniProt reviewed canonical sequence.

>P07949|RET
     1  MAKATSGAAG LRLLLLLLLP LLGKVALGLY FSRDAYWEKL YVDQAAGTPL LYVHALRDAP
    61  EEVPSFRLGQ HLYGTYRTRL HENNWICIQE DTGLLYLNRS LDHSSWEKLS VRNRGFPLLT
   121  VYLKVFLSPT SLREGECQWP GCARVYFSFF NTSFPACSSL KPRELCFPET RPSFRIRENR
   181  PPGTFHQFRL LPVQFLCPNI SVAYRLLEGE GLPFRCAPDS LEVSTRWALD REQREKYELV
   241  AVCTVHAGAR EEVVMVPFPV TVYDEDDSAP TFPAGVDTAS AVVEFKRKED TVVATLRVFD
   301  ADVVPASGEL VRRYTSTLLP GDTWAQQTFR VEHWPNETSV QANGSFVRAT VHDYRLVLNR
   361  NLSISENRTM QLAVLVNDSD FQGPGAGVLL LHFNVSVLPV SLHLPSTYSL SVSRRARRFA
   421  QIGKVCVENC QAFSGINVQY KLHSSGANCS TLGVVTSAED TSGILFVNDT KALRRPKCAE
   481  LHYMVVATDQ QTSRQAQAQL LVTVEGSYVA EEAGCPLSCA VSKRRLECEE CGGLGSPTGR
   541  CEWRQGDGKG ITRNFSTCSP STKTCPDGHC DVVETQDINI CPQDCLRGSI VGGHEPGEPR
   601  GIKAGYGTCN CFPEEEKCFC EPEDIQDPLC DELCRTVIAA AVLFSFIVSV LLSAFCIHCY
   661  HKFAHKPPIS SAEMTFRRPA QAFPVSYSSS GARRPSLDSM ENQVSVDAFK ILEDPKWEFP
   721  RKNLVLGKTL GEGEFGKVVK ATAFHLKGRA GYTTVAVKML KENASPSELR DLLSEFNVLK
   781  QVNHPHVIKL YGACSQDGPL LLIVEYAKYG SLRGFLRESR KVGPGYLGSG GSRNSSSLDH
   841  PDERALTMGD LISFAWQISQ GMQYLAEMKL VHRDLAARNI LVAEGRKMKI SDFGLSRDVY
   901  EEDSYVKRSQ GRIPVKWMAI ESLFDHIYTT QSDVWSFGVL LWEIVTLGGN PYPGIPPERL
   961  FNLLKTGHRM ERPDNCSEEM YRLMLQCWKQ EPDKRPVFAD ISKDLEKMMV KRRDYLDLAA
  1021  STPSDSLIYD DGLSEEETPL VDCNNAPLPR ALPSTWIENK LYGMSDPNWP GESPVPLTRA
  1081  DGTNTGFPRY PNDSVYANWM LSPSAAKLMD TFDS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RET 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
1
Mean surface accessibility (rSASA)
0.34
Highest tissue expression
19 nTPM

Expression across tissuesHPA

Tissue

  • parathyroid gland: 19 nTPM
  • adrenal gland: 11 nTPM
  • midbrain: 6.7 nTPM
  • salivary gland: 3.2 nTPM
  • skeletal muscle: 3 nTPM
  • pituitary gland: 2.2 nTPM

Single-cell type

  • adrenal medulla cells: 234 nCPM
  • respiratory ionocytes: 86 nCPM
  • retinal horizontal cells: 86 nCPM
  • breast lactating cells: 63 nCPM
  • fibro-adipogenic progenitors: 52 nCPM
  • corticotrophs: 36 nCPM

Immune cell

  • plasmacytoid DC: 0.7 nTPM
  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM

Brain region

  • midbrain: 67 nTPM
  • medulla oblongata: 37 nTPM
  • pons: 30 nTPM
  • thalamus: 21 nTPM
  • white matter: 15 nTPM
  • hypothalamus: 14 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RET.

Disease | AllUniProt

Conditions RET is implicated in, by any mechanism.

Disease | GeneticClinVar

172 pathogenic / likely-pathogenic of 4,386 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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)
0.12
gnomAD pLI
1
gnomAD missense Z
0.96
DepMap mean gene effect
-0.1
DepMap dependency class
selective

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

RET is annotated at the cell surface, where native RET 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 RET as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/RET. 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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