RET Gene (Protein Coding)

Ret Proto-Oncogene

GC10P043081
GIFtS:
54
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 s... See more...

Aliases for RET Gene

Aliases for RET Gene

  • Ret Proto-Oncogene 2 3 5
  • CDHF12 2 3 4
  • CDHR16 2 3 4
  • PTC 2 3 4
  • Proto-Oncogene Tyrosine-Protein Kinase Receptor Ret 3 4
  • Cadherin-Related Family Member 16 2 3
  • Rearranged During Transfection 2 3
  • RET Receptor Tyrosine Kinase 2 3
  • Cadherin Family Member 12 3 4
  • Proto-Oncogene C-Ret 3 4
  • EC 2.7.10.1 4 51
  • RET51 2 4
  • Ret Proto-Oncogene (Multiple Endocrine Neoplasia And Medullary Thyroid Carcinoma 1, Hirschsprung Disease) 3
  • Multiple Endocrine Neoplasia And Medullary Thyroid Carcinoma 1 2
  • Hirschsprung Disease 1 2
  • EC 2.7.10 51
  • RET-ELE1 3
  • HSCR1 3
  • MEN2A 3
  • MEN2B 3
  • MTC1 3
  • RET 5

External Ids for RET Gene

Previous HGNC Symbols for RET Gene

  • HSCR1
  • MEN2A
  • MTC1
  • MEN2B

Previous GeneCards Identifiers for RET Gene

  • GC10P042861
  • GC10P043040
  • GC10P043347
  • GC10P042856
  • GC10P042892
  • GC10P043572
  • GC10P040098

Summaries for RET Gene

Entrez Gene Summary for RET 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]

CIViC Summary for RET Gene

  • RET mutations and the RET fusion RET-PTC lead to activation of this tyrosine kinase receptor and are associated with thyroid cancers. RET point mutations are the most common mutations identified in medullary thyroid cancer (MTC) with germline and somatic mutations in RET associated with hereditary and sporadic forms, respectively. The most common somatic form mutation is M918T (exon 16) and a variety of other mutations effecting exons 10, 11 and 15 have been described. The prognostic significance of these mutations have been hotly debated in the field, however, data suggests that some RET mutation may confer drug resistence. No RET-specific agents are currently clinically available but several promiscuous kinase inhibitors that target RET, among others, have been approved for MTC treatment.

GeneCards Summary for RET Gene

RET (Ret Proto-Oncogene) is a Protein Coding gene. Diseases associated with RET include Multiple Endocrine Neoplasia, Type Iia and Thyroid Carcinoma, Familial Medullary. Among its related pathways are Signaling by GPCR and Central carbon metabolism in cancer. Gene Ontology (GO) annotations related to this gene include calcium ion binding and protein kinase activity. An important paralog of this gene is PDGFRA.

UniProtKB/Swiss-Prot Summary for RET Gene

  • Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846097, PubMed:28953886, PubMed:28846099). Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL (PubMed:28846099).

Tocris Summary for RET Gene

Gene Wiki entry for RET Gene

Additional gene information for RET Gene

No data available for PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RET Gene

Genomics for RET Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for RET Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH10J043077 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 250.7 +0.1 137 1.6 ZIC2 ZNF341 CTBP1 SIN3A SP2 CTCF POLR2A HDAC2 ZNF561 RFX5 HSALNG0077523 NONHSAG005699.2 RET CSGALNACT2
GH10J043079 Enhancer 0.3 Ensembl 250.7 +1.4 1437 0.2 ZNF18 HSALNG0077523 NONHSAG005699.2 RET lnc-RASGEF1A-3 CSGALNACT2
GH10J043104 Promoter/Enhancer 1.8 FANTOM5 Ensembl ENCODE CraniofacialAtlas 12.8 +28.2 28207 1.7 ZBTB10 CTCF BHLHE40 ZIC2 ZNF610 THAP11 SIN3A REST ZNF639 VEZF1 CSGALNACT2 RET RASGEF1A piR-37551 CSGALNACT2-DT
GH10J042951 Enhancer 1 VISTA ENCODE 7.4 -124.7 -124673 1.6 ZIC2 SIN3A ZNF341 MYC MAX CTCF EGR1 GLIS1 ZFP69B KLF1 RET ENSG00000259869 LINC00839 ZNF33B lnc-RET-3 HSALNG0077517 BMS1
GH10J042933 Enhancer 0.6 ENCODE 11.5 -143.1 -143050 1.8 ZIC2 INSM2 TAF1 CEBPG NFIB CREM CREB1 CEBPB EZH2 ZNF629 RET LOC441666 ENSG00000259869 ZNF33B HSALNG0077516 lnc-RET-3 BMS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RET on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RET

Top Transcription factor binding sites by QIAGEN in the RET gene promoter:
  • AP-1
  • NF-1
  • NF-1/L
  • STAT3

Genomic Locations for RET Gene

Latest Assembly
chr10:43,077,064-43,130,351
(GRCh38/hg38)
Size:
53,288 bases
Orientation:
Plus strand

Previous Assembly
chr10:43,572,517-43,625,799
(GRCh37/hg19 by Entrez Gene)
Size:
53,283 bases
Orientation:
Plus strand

chr10:43,572,475-43,625,799
(GRCh37/hg19 by Ensembl)
Size:
53,325 bases
Orientation:
Plus strand

Genomic View for RET Gene

Genes around RET on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RET Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RET Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for RET Gene

Proteins for RET Gene

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  • Protein details for RET Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P07949-RET_HUMAN
    Recommended name:
    Proto-oncogene tyrosine-protein kinase receptor Ret
    Protein Accession:
    P07949
    Secondary Accessions:
    • A8K6Z2
    • Q15250
    • Q9BTB0
    • Q9H4A2

    Protein attributes for RET Gene

    Size:
    1114 amino acids
    Molecular mass:
    124319 Da
    Quaternary structure:
    • Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5 (By similarity). The phosphorylated form interacts with PLCG1 and GRB7 (By similarity). Interacts (not phosphorylated) with PTK2/FAK1 (via FERM domain) (PubMed:21454698). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas (PubMed:21357690). Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex (PubMed:19366855). Binds to ARTN (By similarity). Interacts (inactive) with CBLC and CD2AP; dissociates upon activation by GDNF which increases CBLC:CD2AP interaction (PubMed:18753381). Interacts (via the extracellular domain) with GFRAL (via the extracellular domain); the interaction mediates cellular signaling upon interaction of GFRAL with its ligand GDF15 (PubMed:28953886, PubMed:28846097, PubMed:28846099). Interaction with GFRAL requires previous GDF15-binding to GFRAL (PubMed:28846097, PubMed:28846099). Interacts with GFRA1; in the presence of SORL1, the GFRA1/RET complex is targeted to endosomes (PubMed:23333276). Interacts with GDNF (PubMed:21994944).
    SequenceCaution:
    • Sequence=AAA36524.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAA36786.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA33787.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAC14882.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
    Miscellaneous:
    • Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC).

    Three dimensional structures from OCA and Proteopedia for RET Gene

    Alternative splice isoforms for RET Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RET Gene

Protein Expression for RET Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for RET Gene

P07949:
  • RDLAARN
  • VAVKMLK
  • WMAIESL

Post-translational modifications for RET Gene

  • Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. Dephosphorylated by PTPRJ on Tyr-905, Tyr-1015 and Tyr-1062.
  • Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell-membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons.
  • Glycosylation at Asn98, Asn151, Asn199, Asn336, Asn343, Asn361, Asn367, Asn377, Asn394, Asn448, Asn468, and Asn554
  • Modification sites at PhosphoSitePlus

Other Protein References for RET Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for RET

Domains & Families for RET Gene

Gene Families for RET Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for RET Gene

InterPro:
Blocks:
  • Tyrosine protein kinase, active site
  • Cadherin
ProtoNet:

Suggested Antigen Peptide Sequences for RET Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58503, highly similar to Proto-oncogene tyrosine-protein kinase receptorret (EC 2.7.10.1) (B4DGX8_HUMAN)
  • Ret proto-oncogene tyrosine-protein kinase receptor isoform a (F8TLS5_HUMAN)
  • Ret proto-oncogene tyrosine-protein kinase receptor isoform a (F8TLW0_HUMAN)
  • RET proto-oncogene (O43519_HUMAN)
  • Ret proto-oncogene (Q8IZR8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P07949

UniProtKB/Swiss-Prot:

RET_HUMAN :
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
genes like me logo Genes that share domains with RET: view

Function for RET Gene

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  6. Cell Lines for research

Molecular function for RET Gene

UniProtKB/Swiss-Prot Function:
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846097, PubMed:28953886, PubMed:28846099). Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL (PubMed:28846099).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};.
UniProtKB/Swiss-Prot Induction:
Positively regulated by NKX2-1, PHOX2B, SOX10 and PAX3.
UniProtKB/Swiss-Prot EnzymeRegulation:
Repressed by 4-(3-hydroxyanilino)-quinolines derivatives, indolin-2-one-derivatives, 2-(alkylsulfanyl)-4-(3-thienyl) nicotinonitrile analogs, 3- and 4-substituted beta-carbolin-1-ones, vandetanib, motesanib, sorafenib (BAY 43-9006), cabozantinib (XL184), sunitinib, and withaferin A (WA). Inactivation by sorafenib both reduces kinase activity and promotes lysosomal degradation.
GENATLAS Biochemistry:
glial cell line derived neurotrophic factor (GDNF) receptor component,homodimerizing and binding the GDNF-GFRA complex,expressed in the developing kidney,the presumptive enteric neuroblats,cranial ganglia (VII,VIII,IX and X) and in the presumptive motor neurons of the spinal cord,interacting with SHC1 transduction adaptor protein,potentially involved in peripheral nerve repair

Enzyme Numbers (IUBMB) for RET Gene

Phenotypes From GWAS Catalog for RET Gene

Gene Ontology (GO) - Molecular Function for RET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA --
GO:0004713 protein tyrosine kinase activity TAS 7824936
GO:0004714 transmembrane receptor protein tyrosine kinase activity TAS --
GO:0005509 calcium ion binding IEA,IDA 11445581
genes like me logo Genes that share ontologies with RET: view
genes like me logo Genes that share phenotypes with RET: view

Human Phenotype Ontology for RET Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RET Gene

MGI Knock Outs for RET:
  • Ret Ret<tm5(RET)Jmi>
  • Ret Ret<tm6(RET)Jmi>
  • Ret Ret<tm1.1Kln>
  • Ret Ret<tm1.2Pern>
  • Ret Ret<tm13.1Jmi>
  • Ret Ret<tm1Cos>
  • Ret Ret<tm1Cti>
  • Ret Ret<tm1Heno>
  • Ret Ret<tm1Jmi>
  • Ret Ret<tm2.1Heno>
  • Ret Ret<tm6.2Vpa>

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RET

Clone products for research

  • Addgene plasmids for RET

No data available for Transcription Factor Targets and HOMER Transcription for RET Gene

Localization for RET Gene

Subcellular locations from UniProtKB/Swiss-Prot for RET Gene

Cell membrane. Single-pass type I membrane protein. Endosome membrane. Single-pass type I membrane protein. Note=Predominantly located on the plasma membrane. In the presence of SORL1 and GFRA1, directed to endosomes. {ECO:0000269 PubMed:23333276}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RET gene
Compartment Confidence
plasma membrane 5
endosome 5
extracellular 3
nucleus 3
cytosol 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
lysosome 2
golgi apparatus 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Cytosol (2)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IBA,IDA 19823924
GO:0010008 endosome membrane IEA,IDA 19823924
genes like me logo Genes that share ontologies with RET: view

Pathways & Interactions for RET Gene

PathCards logo

SuperPathways for RET Gene

SuperPathway Contained pathways
1 RET signaling
Frs2-mediated activation
.95
GRB2 events in EGFR signaling
.95
MAPK1/MAPK3 signaling
.95
Prolonged ERK activation events
.95
RAF/MAP kinase cascade
.95
SHC1 events in EGFR signaling
.95
Signaling by Leptin
.95
SOS-mediated signalling
.95
VEGFR2 mediated cell proliferation
.95
ARMS-mediated activation
.95
Signalling to ERKs
.95
Signalling to p38 via RIT and RIN
.95
Signalling to RAS
.95
Interleukin receptor SHC signaling
.95
Interleukin-3, 5 and GM-CSF signaling
.94
Interleukin-2 signaling
.94
Downstream signal transduction
.94
Signaling by PDGF
.94
DAP12 signaling
.92
RET signaling
.92
Insulin receptor signalling cascade
.92
Signaling by Insulin receptor
.92
IRS-mediated signalling
.91
Signaling by EGFR
.90
FCERI mediated MAPK activation
.90
IGF1R signaling cascade
.90
IRS-related events triggered by IGF1R
.90
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
.90
DAP12 interactions
.89
NCAM signaling for neurite out-growth
.89
NGF signalling via TRKA from the plasma membrane
.87
MAPK family signaling cascades
.87
Signaling by SCF-KIT
.85
Signalling by NGF
.81
Fc epsilon receptor (FCERI) signaling
.79
VEGFA-VEGFR2 Pathway
.78
Signaling by VEGF
.76
Gastrin-CREB signalling pathway via PKC and MAPK
.55
2 Developmental Biology
Axon guidance
.51
Developmental Biology
.51
3 Cytokine Signaling in Immune system
Cytokine Signaling in Immune system
.69
Signaling by Interleukins
.69
4 Innate Immune System
Immune System
.61
Innate Immune System
.61
5 Signaling by GPCR
Signaling by GPCR
.76
Signal Transduction
.52
genes like me logo Genes that share pathways with RET: view

Pathways by source for RET Gene

1 PharmGKB pathway for RET Gene
2 GeneGo (Thomson Reuters) pathways for RET Gene
  • Development GDNF family signaling
  • G-protein signaling_H-RAS regulation pathway
2 Cell Signaling Technology pathways for RET Gene

SIGNOR curated interactions for RET Gene

Activates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for RET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0000187 activation of MAPK activity IMP 28953886
GO:0001657 ureteric bud development IEA --
GO:0001755 neural crest cell migration IEA --
GO:0001838 embryonic epithelial tube formation IEA --
genes like me logo Genes that share ontologies with RET: view

Drugs & Compounds for RET Gene

Products:

  1. Drug products for research

(76) Drugs for RET Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cabozantinib Approved, Investigational Pharma Target, antagonist, inhibitor Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
Vandetanib Approved Pharma Target, inhibitor, Biomarker VEGFR, EGFR, and RET inhibitor, EGFR Inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
regorafenib Approved Pharma Target, inhibitor Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
imatinib Approved Pharma Target, inhibitor Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors 0
Sorafenib Approved, Investigational Pharma Target, inhibitor, inhibitors Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 795

(20) Additional Compounds for RET Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 58-64-0

(12) ApexBio Compounds for RET Gene

Compound Action Cas Number
Amuvatinib (MP-470, HPK 56) Tyrosine kinase inhibitor 850879-09-3
Apatinib VEGFR2 inhibitor, orally bioavailable, selective 811803-05-1
AST 487 RET kinase inhibitor 630124-46-8
Cabozantinib (XL184, BMS-907351) VEGFR2/Met/Ret/Kit/FLT//AXL inhibitor 849217-68-1
Danusertib (PHA-739358) Pan-aurora kinase inhibitor 827318-97-8
Motesanib Diphosphate (AMG-706) VEGFR/ PDGFR/c-Kit/Ret inhibitor 857876-30-3
Regorafenib Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1 755037-03-7
Regorafenib hydrochloride 835621-07-3
Regorafenib monohydrate Tyrosine kinase inhibitor 1019206-88-2
SU5416 VEGF receptor inhibitor and AHR agonist 204005-46-9
Sunitinib malate VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor 341031-54-7
TG101209 JAK2/3 inhibitor 936091-14-4
genes like me logo Genes that share compounds with RET: view

Drug products for research

Transcripts for RET Gene

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mRNA/cDNA for RET Gene

5 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RET

Clone products for research

  • Addgene plasmids for RET

Alternative Splicing Database (ASD) splice patterns (SP) for RET Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20
SP1: -
SP2:
SP3: - - - - - - - - -
SP4: - - - - - - - -

Relevant External Links for RET Gene

GeneLoc Exon Structure for
RET

Expression for RET Gene

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  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RET Gene

mRNA expression in normal human tissues for RET Gene
mRNA expression by GTEx for RET GenemRNA expression by BioGPS for RET Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RET Gene

This gene is overexpressed in Brain - Substantia nigra (x7.2).

Protein differential expression in normal tissues from HIPED for RET Gene

This gene is overexpressed in Cervix (61.5) and Peripheral blood mononuclear cells (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RET Gene



Protein tissue co-expression partners for RET Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RET

SOURCE GeneReport for Unigene cluster for RET Gene:

Hs.350321

Evidence on tissue expression from TISSUES for RET Gene

  • Nervous system(4.8)
  • Blood(4.5)
  • Thyroid gland(3.2)
  • Adrenal gland(3)
  • Intestine(2.8)
  • Lymph node(2.5)
  • Skin(2.3)
  • Kidney(2.2)
  • Muscle(2.2)
  • Eye(2.1)
  • Liver(2.1)
  • Heart(2)
  • Bone marrow(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RET Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • larynx
  • lip
  • mandible
  • maxilla
  • meninges
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • parathyroid
  • pituitary gland
  • skull
  • thyroid
  • tongue
  • vocal cord
Thorax:
  • breast
  • chest wall
  • clavicle
  • diaphragm
  • esophagus
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
  • trachea
Abdomen:
  • adrenal gland
  • duodenum
  • intestine
  • kidney
  • large intestine
  • pancreas
  • small intestine
  • stomach
Pelvis:
  • ovary
  • pelvis
  • placenta
  • rectum
  • ureter
  • urethra
  • urinary bladder
  • uterus
  • vagina
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • sweat gland
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with RET: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt for RET Gene

Orthologs for RET Gene

This gene was present in the common ancestor of animals.

Orthologs for RET Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia RET 30 31
  • 96.18 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia RET 30 31
  • 87.04 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia RET 30 31
  • 86.4 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Ret 30
  • 83.33 (n)
Mouse
(Mus musculus)
 Mammalia Ret 30 17 31
  • 82.78 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia RET 31
  • 74 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia RET 31
  • 59 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves RET 30 31
  • 66.44 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia RET 31
  • 60 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia ret 30
  • 64.3 (n)
African clawed frog
(Xenopus laevis)
 Amphibia ret-A 30
Zebrafish
(Danio rerio)
 Actinopterygii ret 30 31
  • 63.74 (n)
 OneToOne
ret1 30
Fruit Fly
(Drosophila melanogaster)
 Insecta tor 32
  • 49 (a)
Ret 31 32
  • 28 (a)
 OneToOne
Worm
(Caenorhabditis elegans)
 Secernentea R151.4 32
  • 39 (a)
C24G6.2a 32
  • 37 (a)
C24G6.2b 32
  • 37 (a)
kin-9 32
  • 36 (a)
Y50D4B.6 32
  • 33 (a)
F09A5.2 32
  • 33 (a)
kin-16 32
  • 33 (a)
ver-4 32
  • 33 (a)
Y38H6C.20 32
  • 31 (a)
W01B6.5 32
  • 30 (a)
F59A3.8 32
  • 30 (a)
R09D1.12 32
  • 29 (a)
F09G2.1 32
  • 27 (a)
Species where no ortholog for RET was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for RET Gene

ENSEMBL:
Gene Tree for RET (if available)
TreeFam:
Gene Tree for RET (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RET: view image

Paralogs for RET Gene

Paralogs for RET Gene

(64) SIMAP similar genes for RET Gene using alignment to 14 proteins:

  • RET_HUMAN
  • B4DGX8_HUMAN
  • C9JYL6_HUMAN
  • F8TLS5_HUMAN
  • F8TLW0_HUMAN
  • L8EA94_HUMAN
  • M9Z0T2_HUMAN
  • O43519_HUMAN
  • Q8IZR8_HUMAN
  • Q8NFE8_HUMAN
  • Q99886_HUMAN
  • Q9BTX6_HUMAN
  • Q9UM90_HUMAN
  • Q9UMQ4_HUMAN
genes like me logo Genes that share paralogs with RET: view

Variants for RET Gene

Products:

  1. SNP Genotyping and Copy Number Assays for research

Polymorphic Variants from UniProtKB/Swiss-Prot for RET Gene

RET_HUMAN-P07949
The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RET Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
477312 Uncertain Significance: Multiple endocrine neoplasia, type 2 43,111,238(+) CA/TG
NM_020975.6(RET):c.1295_1296inv (p.Ala432Val) 		MISSENSE
834355 Uncertain Significance: Multiple endocrine neoplasia, type 2 43,126,674(+) C/T
NM_020975.6(RET):c.3139C>T (p.Pro1047Ser) 		MISSENSE
834358 Uncertain Significance: Multiple endocrine neoplasia, type 2 43,118,432(+) G/T
NM_020975.6(RET):c.2344G>T (p.Val782Phe) 		MISSENSE
834470 Uncertain Significance: Multiple endocrine neoplasia, type 2 43,126,719(+) T/G
NM_020975.6(RET):c.3184T>G (p.Tyr1062Asp) 		MISSENSE
835920 Uncertain Significance: Multiple endocrine neoplasia, type 2 43,077,301(+) TTGCTGC/T
NM_020975.6(RET):c.44_46TGC[3] (p.Leu18_Leu19del) 		INFRAME_DELETION

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RET Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RET Gene

Variant ID Type Subtype PubMed ID
dgv723n100 CNV gain 25217958
dgv724n100 CNV gain 25217958
dgv725n100 CNV gain 25217958
dgv726n100 CNV gain 25217958
dgv727n100 CNV gain 25217958
esv275022 CNV gain+loss 21479260
nsv1038102 CNV gain 25217958
nsv1042310 CNV loss 25217958
nsv1052276 CNV gain 25217958
nsv1143500 CNV deletion 24896259
nsv1161940 CNV duplication 26073780
nsv522566 CNV loss 19592680
nsv522592 CNV loss 19592680
nsv550695 CNV gain 21841781
nsv825350 CNV gain 20364138
nsv951564 CNV deletion 24416366

Variation tolerance for RET Gene

Residual Variation Intolerance Score: 11.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.47; 77.48% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RET Gene

Human Gene Mutation Database (HGMD)
RET
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RET

SNP Genotyping and Copy Number Assays for research

Disorders for RET Gene

MalaCards: The human disease database

(135) MalaCards diseases for RET Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search RET in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RET_HUMAN
  • Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The disease may be caused by variants affecting the gene represented in this entry.
  • Hirschsprung disease 1 (HSCR1) [MIM:142623]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. {ECO:0000269 PubMed:10090908, ECO:0000269 PubMed:10484767, ECO:0000269 PubMed:10618407, ECO:0000269 PubMed:22174939, ECO:0000269 PubMed:7581377, ECO:0000269 PubMed:7633441, ECO:0000269 PubMed:7704557, ECO:0000269 PubMed:7881414, ECO:0000269 PubMed:8114938, ECO:0000269 PubMed:8114939, ECO:0000269 PubMed:9043870, ECO:0000269 PubMed:9090527, ECO:0000269 PubMed:9094028, ECO:0000269 PubMed:9259198, ECO:0000269 PubMed:9384613, ECO:0000269 Ref.62}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Medullary thyroid carcinoma (MTC) [MIM:155240]: Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation. {ECO:0000269 PubMed:10323403, ECO:0000269 PubMed:10826520, ECO:0000269 PubMed:11692159, ECO:0000269 PubMed:7784092, ECO:0000269 PubMed:7845675, ECO:0000269 PubMed:7849720, ECO:0000269 PubMed:7874109, ECO:0000269 PubMed:7881414, ECO:0000269 PubMed:7915165, ECO:0000269 PubMed:8103403, ECO:0000269 PubMed:8557249, ECO:0000269 PubMed:8625130, ECO:0000269 PubMed:8807338, ECO:0000269 PubMed:9223675, ECO:0000269 PubMed:9259198, ECO:0000269 PubMed:9398735, ECO:0000269 PubMed:9452077, ECO:0000269 PubMed:9506724, ECO:0000269 PubMed:9621513, ECO:0000269 PubMed:9677065}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Multiple neoplasia 2B (MEN2B) [MIM:162300]: Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases. {ECO:0000269 PubMed:7906417, ECO:0000269 PubMed:7906866, ECO:0000269 PubMed:7911697, ECO:0000269 PubMed:8595427, ECO:0000269 PubMed:8807338, ECO:0000269 PubMed:9294615, ECO:0000269 PubMed:9360560}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269 PubMed:12000816}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
  • Multiple neoplasia 2A (MEN2A) [MIM:171400]: The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism. {ECO:0000269 PubMed:10522989, ECO:0000269 PubMed:7860065, ECO:0000269 PubMed:7874109, ECO:0000269 PubMed:7881414, ECO:0000269 PubMed:7915165, ECO:0000269 PubMed:8099202, ECO:0000269 PubMed:8103403, ECO:0000269 PubMed:8626834, ECO:0000269 PubMed:8807338, ECO:0000269 PubMed:9097963, ECO:0000269 PubMed:9384613, ECO:0000269 PubMed:9452064}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Note=Various chromosomal aberrations involving RET are known. Some of them have been found in papillary thyroid carcinomas (PTCs) (PubMed:12787916, PubMed:2406025, PubMed:10980597, PubMed:10439047). Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene (PubMed:2406025). Inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene. Translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene (PubMed:2734021). Translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion (PubMed:10980597). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the Delta RFP/RET oncogene (PubMed:12787916). Translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene (PubMed:10439047). Translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene (PubMed:10439047). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the TRIM27/RET oncogene (PubMed:3037315). {ECO:0000269 PubMed:10439047, ECO:0000269 PubMed:10980597, ECO:0000269 PubMed:12787916, ECO:0000269 PubMed:2406025, ECO:0000269 PubMed:2734021, ECO:0000269 PubMed:3037315}.
  • Note=Mutations in RET have been detected in patients with renal agenesis suggesting a possible involvement of this gene in disease pathogenesis.
  • Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269 PubMed:12086152, ECO:0000269 PubMed:14566559, ECO:0000269 PubMed:9497256}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for RET

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Tumor Gene Family of Databases
(TGDB)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with RET: view

No data available for Genatlas for RET Gene

Publications for RET Gene

  1. Germ-line mutations in nonsyndromic pheochromocytoma. (PMID: 12000816) Neumann HP … Freiburg-Warsaw-Columbus Pheochromocytoma Study Group (The New England journal of medicine 2002) 3 4 23 41 74
  2. A novel 9-base pair duplication in RET exon 8 in familial medullary thyroid carcinoma. (PMID: 10323403) Pigny P … Porchet N (The Journal of clinical endocrinology and metabolism 1999) 3 4 23 74
  3. A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene. (PMID: 10522989) Tessitore A … Colantuoni V (The Journal of clinical endocrinology and metabolism 1999) 3 4 23 41
  4. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. (PMID: 8114938) Romeo G … Kääriäinen H (Nature 1994) 3 4 23 74
  5. Reduced RET expression in gut tissue of individuals carrying risk alleles of Hirschsprung's disease. (PMID: 20089534) Miao X … Garcia-Barceló M (Human molecular genetics 2010) 3 23 41

ExternalLinks

View latest publications for RET gene in Mastermind

Products for RET Gene