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

Gene ID: 5979, updated on 20-Apr-2024

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; AllianceGenome:HGNC:9967
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Location:
10q11.21
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (43077069..43130351)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (43954542..44007848)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (43572517..43625799)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene VISTA enhancer hs2497 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43483113-43483758 Neighboring gene long intergenic non-protein coding RNA 1264 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43485513-43486245 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43492878-43493378 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43495973-43496668 Neighboring gene microRNA 5100 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:43507236-43508231 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:43508232-43509226 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43521134-43521642 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:43521643-43522150 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43522661-43523168 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43535603-43536323 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43539799-43540690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43540691-43541582 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43544190-43544720 Neighboring gene VISTA enhancer hs2498 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43557619-43558120 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43558121-43558620 Neighboring gene RET 5' regulatory region Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:43572872-43573862 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43580156-43580656 Neighboring gene VISTA enhancer hs2326 Neighboring gene RET intron 1 enhancer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43596873-43597372 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43600219-43600970 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2313 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3282 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:43604510-43604673 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3283 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3284 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3285 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3286 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:43625782-43626382 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:43626383-43626983 Neighboring gene CSGALNACT2 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2314 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2315 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2316 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2317 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2318 Neighboring gene chondroitin sulfate N-acetylgalactosaminyltransferase 2 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:43655229-43656428 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_12290

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

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

EBI GWAS Catalog

Description
A genome-wide association study identifies potential susceptibility Loci for hirschsprung disease.
EBI GWAS Catalog
Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.
EBI GWAS Catalog

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by GOA

Process Evidence Code Pubs
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
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 cell surface receptor protein tyrosine kinase signaling pathway IBA
Inferred from Biological aspect of Ancestor
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
 
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 positive regulation of DNA-templated transcription ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of MAPK cascade IMP
Inferred from Mutant Phenotype
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
 
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 phosphatidylinositol 3-kinase/protein kinase B signal transduction IMP
Inferred from Mutant Phenotype
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 pain ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
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 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
 
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 
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
is_active_in plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
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
 
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_001393672.1
NP_001393673.1
NP_001393688.1
NP_001393689.1
NP_001393690.1
NP_001393691.1
NP_001393692.1
NP_001393693.1
NP_001393694.1
NP_001393695.1
NP_001393696.1
NP_001393697.1
NP_001393698.1
NP_001393699.1
NP_001393700.1
NP_001393701.1
NP_001393702.1
NP_001393703.1
NP_001393704.1
NP_001393705.1
NP_001393706.1
NP_001393707.1
NP_001393708.1
NP_001393709.1
NP_001393710.1
NP_001393711.1
NP_001393712.1
NP_001393713.1
NP_001393714.1
NP_001393715.1
NP_001393716.1
NP_001393717.1
NP_001393718.1
NP_001393719.1
NP_001393720.1
NP_001393721.1
NP_001393722.1
NP_001393723.1
NP_065681.1
NP_066124.1

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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_001355216.2NP_001342145.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform d

    Status: REVIEWED

    Source sequence(s)
    AC010864
    UniProtKB/TrEMBL
    B4DGX8
    Related
    ENST00000683007.1
    Conserved Domains (1) summary
    cd05045
    Location:469758
    PTKc_RET; Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein
  2. NM_001406743.1NP_001393672.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform a precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
    UniProtKB/Swiss-Prot
    A8K6Z2, P07949, Q9BTB0
  3. NM_001406744.1NP_001393673.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform b precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  4. NM_001406759.1NP_001393688.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform e precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  5. NM_001406760.1NP_001393689.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform e precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  6. NM_001406761.1NP_001393690.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform f precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  7. NM_001406762.1NP_001393691.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform f precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  8. NM_001406763.1NP_001393692.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform g precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  9. NM_001406764.1NP_001393693.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform h precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  10. NM_001406765.1NP_001393694.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform i precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  11. NM_001406766.1NP_001393695.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform j precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  12. NM_001406767.1NP_001393696.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform j precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  13. NM_001406768.1NP_001393697.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform k precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  14. NM_001406769.1NP_001393698.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform l precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  15. NM_001406770.1NP_001393699.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform m precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  16. NM_001406771.1NP_001393700.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform n precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  17. NM_001406772.1NP_001393701.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform o precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
    UniProtKB/TrEMBL
    A0A087WWB1
    Related
    ENSP00000480088.2, ENST00000615310.5
  18. NM_001406773.1NP_001393702.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform p precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  19. NM_001406774.1NP_001393703.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform q precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  20. NM_001406775.1NP_001393704.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform r precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  21. NM_001406776.1NP_001393705.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform s precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  22. NM_001406777.1NP_001393706.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform t precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  23. NM_001406778.1NP_001393707.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform u precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  24. NM_001406779.1NP_001393708.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform v precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  25. NM_001406780.1NP_001393709.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform v precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  26. NM_001406781.1NP_001393710.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform w precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  27. NM_001406782.1NP_001393711.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform x precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  28. NM_001406783.1NP_001393712.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform y precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  29. NM_001406784.1NP_001393713.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform z precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  30. NM_001406785.1NP_001393714.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform aa precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  31. NM_001406786.1NP_001393715.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform bb precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  32. NM_001406787.1NP_001393716.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform cc precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  33. NM_001406788.1NP_001393717.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform dd precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  34. NM_001406789.1NP_001393718.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform dd precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  35. NM_001406790.1NP_001393719.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform ff precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  36. NM_001406791.1NP_001393720.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform gg precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  37. NM_001406792.1NP_001393721.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform hh precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  38. NM_001406793.1NP_001393722.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform ii precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  39. NM_001406794.1NP_001393723.1  proto-oncogene tyrosine-protein kinase receptor Ret isoform jj precursor

    Status: REVIEWED

    Source sequence(s)
    AC010864
  40. NM_020630.7NP_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

    Source sequence(s)
    AC010864
    Consensus CDS
    CCDS53525.1
    UniProtKB/TrEMBL
    F8TLW0
    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
  41. 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

    Source sequence(s)
    AC010864, BC003072, BC004257, BM661773, X12949
    Consensus CDS
    CCDS7200.1
    UniProtKB/Swiss-Prot
    A8K6Z2, P07949, Q9BTB0
    UniProtKB/TrEMBL
    F8TLW0
    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: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

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

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    43954542..44007848
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)