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RET ret proto-oncogene [ Homo sapiens (human) ]

Gene ID: 5979, updated on 22-Jun-2021

Summary

Official Symbol
RETprovided by HGNC
Official Full Name
ret proto-oncogeneprovided by HGNC
Primary source
HGNC:HGNC:9967
See related
Ensembl:ENSG00000165731 MIM:164761
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PTC; MTC1; HSCR1; MEN2A; MEN2B; CDHF12; CDHR16; RET-ELE1
Summary
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]
Expression
Biased expression in adrenal (RPKM 10.2), prostate (RPKM 1.3) and 9 other tissues See more
Orthologs
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Genomic context

See RET in Genome Data Viewer
Location:
10q11.21
Exon count:
20
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 10 NC_000010.11 (43077069..43130351)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (43572517..43625799)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene microRNA 5100 Neighboring gene VISTA enhancer hs2498 Neighboring gene RET 5' regulatory region Neighboring gene VISTA enhancer hs2326 Neighboring gene RET intron 1 enhancer Neighboring gene chondroitin sulfate N-acetylgalactosaminyltransferase 2 Neighboring gene RasGEF domain family member 1A Neighboring gene uncharacterized LOC107984225

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in RET that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Associated conditions

Description Tests
A genome-wide association study identifies potential susceptibility Loci for hirschsprung disease.
GeneReviews: Not available
Congenital central hypoventilation Compare labs
Familial medullary thyroid carcinoma Compare labs
Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.
GeneReviews: Not available
Hirschsprung disease 1
MedGen: C3888239 OMIM: 142623 GeneReviews: Not available
Compare labs
Multiple endocrine neoplasia, type 2 Compare labs
Multiple endocrine neoplasia, type 2a Compare labs
Multiple endocrine neoplasia, type 2b Compare labs
Pheochromocytoma Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2020-08-26)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2020-08-26)

ClinGen Genome Curation PagePubMed

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
 
enables calcium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein tyrosine kinase activity TAS
Traceable Author Statement
more info
PubMed 
enables signaling receptor activity TAS
Traceable Author Statement
more info
PubMed 
enables transmembrane receptor protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables transmembrane receptor protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
involved_in MAPK cascade TAS
Traceable Author Statement
more info
 
involved_in Peyer's patch morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in axon guidance TAS
Traceable Author Statement
more info
 
involved_in cellular response to retinoic acid IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in embryonic epithelial tube formation IEA
Inferred from Electronic Annotation
more info
 
involved_in enteric nervous system development IEA
Inferred from Electronic Annotation
more info
 
involved_in glial cell-derived neurotrophic factor receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
involved_in homophilic cell adhesion via plasma membrane adhesion molecules IEA
Inferred from Electronic Annotation
more info
 
involved_in innervation IEA
Inferred from Electronic Annotation
more info
 
involved_in lymphocyte migration into lymphoid organs ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in membrane protein proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in multicellular organism development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in neural crest cell migration IEA
Inferred from Electronic Annotation
more info
 
involved_in neuron cell-cell adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in neuron maturation IEA
Inferred from Electronic Annotation
more info
 
involved_in peptidyl-tyrosine phosphorylation IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of cell adhesion mediated by integrin IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of cell migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of cell size IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of extrinsic apoptotic signaling pathway in absence of ligand TAS
Traceable Author Statement
more info
PubMed 
involved_in positive regulation of gene expression IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in positive regulation of metanephric glomerulus development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of neuron maturation IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of neuron projection development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of peptidyl-serine phosphorylation of STAT protein IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of protein kinase B signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in posterior midgut development TAS
Traceable Author Statement
more info
PubMed 
involved_in protein phosphorylation TAS
Traceable Author Statement
more info
PubMed 
involved_in regulation of axonogenesis IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
involved_in response to drug IEA
Inferred from Electronic Annotation
more info
 
involved_in response to pain ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in retina development in camera-type eye IEA
Inferred from Electronic Annotation
more info
 
involved_in signal transduction TAS
Traceable Author Statement
more info
PubMed 
involved_in transmembrane receptor protein tyrosine kinase signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in ureter maturation IEA
Inferred from Electronic Annotation
more info
 
involved_in ureteric bud development IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
is_active_in axon IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in dendrite IEA
Inferred from Electronic Annotation
more info
 
located_in early endosome IEA
Inferred from Electronic Annotation
more info
 
located_in endosome membrane IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in membrane raft IEA
Inferred from Electronic Annotation
more info
 
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
 
part_of plasma membrane protein complex IDA
Inferred from Direct Assay
more info
PubMed 
part_of receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
part_of receptor complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
proto-oncogene tyrosine-protein kinase receptor Ret
Names
RET receptor tyrosine kinase
cadherin family member 12
cadherin-related family member 16
proto-oncogene c-Ret
rearranged during transfection
ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease)
NP_001342145.1
NP_065681.1
NP_066124.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007489.1 RefSeqGene

    Range
    5001..58283
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_518

mRNA and Protein(s)

  1. NM_001355216.1NP_001342145.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform d

    Status: REVIEWED

    Source sequence(s)
    AC010864, AK294827, BC004257, DC351179
    Conserved Domains (1) summary
    cd05045
    Location:469758
    PTKc_RET; Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein
  2. NM_020630.6NP_065681.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform c precursor

    See identical proteins and their annotated locations for NP_065681.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 3' UTR and coding region compared to variant 2. The resulting isoform (c) is shorter and has a distinct C-terminus compared to isoform a. This isoform is also known as Ret9.
    Source sequence(s)
    AC010864, AK294827, BC004257
    Consensus CDS
    CCDS53525.1
    UniProtKB/Swiss-Prot
    P07949
    Related
    ENSP00000344798.4, ENST00000340058.6
    Conserved Domains (3) summary
    cd05045
    Location:7231012
    PTKc_RET; Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein
    pfam00028
    Location:172261
    Cadherin; Cadherin domain
    pfam07714
    Location:7241005
    Pkinase_Tyr; Protein tyrosine kinase
  3. NM_020975.6NP_066124.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform a precursor

    See identical proteins and their annotated locations for NP_066124.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longer transcript and encodes the longer isoform (a). This isoform is also known as Ret51.
    Source sequence(s)
    AC010864, BC003072, BC004257, BM661773, X12949
    Consensus CDS
    CCDS7200.1
    UniProtKB/Swiss-Prot
    P07949
    UniProtKB/TrEMBL
    A0A024R7T2
    Related
    ENSP00000347942.3, ENST00000355710.8
    Conserved Domains (3) summary
    cd05045
    Location:7231012
    PTKc_RET; Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein
    pfam00028
    Location:172261
    Cadherin; Cadherin domain
    pfam07714
    Location:7241005
    Pkinase_Tyr; Protein tyrosine kinase

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p13 Primary Assembly

    Range
    43077069..43130351
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_000323.2: Suppressed sequence

    Description
    NM_000323.2: This RefSeq was permanently suppressed because currently not enough support exists for the transcript and the protein.
  2. NM_020629.2: Suppressed sequence

    Description
    NM_020629.2: This RefSeq was permanently suppressed because currently not enough support exists for the transcript and the protein.
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