Browse RET

Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type I membrane protein Endosome membrane Single-pass type I membrane protein
Domain PF00028 Cadherin domain
PF07714 Protein tyrosine kinase
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).

> Gene Ontology
 
Biological Process GO:0001101 response to acid chemical
GO:0001654 eye development
GO:0001655 urogenital system development
GO:0001656 metanephros development
GO:0001657 ureteric bud development
GO:0001667 ameboidal-type cell migration
GO:0001755 neural crest cell migration
GO:0001822 kidney development
GO:0001823 mesonephros development
GO:0001838 embryonic epithelial tube formation
GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules
GO:0007158 neuron cell-cell adhesion
GO:0007259 JAK-STAT cascade
GO:0007409 axonogenesis
GO:0007423 sensory organ development
GO:0007494 midgut development
GO:0007497 posterior midgut development
GO:0008361 regulation of cell size
GO:0010720 positive regulation of cell development
GO:0010769 regulation of cell morphogenesis involved in differentiation
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0014031 mesenchymal cell development
GO:0014032 neural crest cell development
GO:0014033 neural crest cell differentiation
GO:0014041 regulation of neuron maturation
GO:0014042 positive regulation of neuron maturation
GO:0016331 morphogenesis of embryonic epithelium
GO:0018105 peptidyl-serine phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0018212 peptidyl-tyrosine modification
GO:0021675 nerve development
GO:0021700 developmental maturation
GO:0022604 regulation of cell morphogenesis
GO:0030335 positive regulation of cell migration
GO:0031346 positive regulation of cell projection organization
GO:0032526 response to retinoic acid
GO:0032535 regulation of cellular component size
GO:0032835 glomerulus development
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033136 serine phosphorylation of STAT3 protein
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033139 regulation of peptidyl-serine phosphorylation of STAT protein
GO:0033141 positive regulation of peptidyl-serine phosphorylation of STAT protein
GO:0033555 multicellular organismal response to stress
GO:0033619 membrane protein proteolysis
GO:0033627 cell adhesion mediated by integrin
GO:0033628 regulation of cell adhesion mediated by integrin
GO:0033630 positive regulation of cell adhesion mediated by integrin
GO:0035148 tube formation
GO:0035239 tube morphogenesis
GO:0035799 ureter maturation
GO:0038034 signal transduction in absence of ligand
GO:0040017 positive regulation of locomotion
GO:0042493 response to drug
GO:0042501 serine phosphorylation of STAT protein
GO:0042551 neuron maturation
GO:0043010 camera-type eye development
GO:0045666 positive regulation of neuron differentiation
GO:0045785 positive regulation of cell adhesion
GO:0045793 positive regulation of cell size
GO:0046425 regulation of JAK-STAT cascade
GO:0048265 response to pain
GO:0048469 cell maturation
GO:0048483 autonomic nervous system development
GO:0048484 enteric nervous system development
GO:0048537 mucosal-associated lymphoid tissue development
GO:0048541 Peyer's patch development
GO:0048565 digestive tract development
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048762 mesenchymal cell differentiation
GO:0048799 animal organ maturation
GO:0048863 stem cell differentiation
GO:0048864 stem cell development
GO:0050769 positive regulation of neurogenesis
GO:0050770 regulation of axonogenesis
GO:0050900 leukocyte migration
GO:0051272 positive regulation of cellular component movement
GO:0051962 positive regulation of nervous system development
GO:0055123 digestive system development
GO:0060041 retina development in camera-type eye
GO:0060384 innervation
GO:0060485 mesenchyme development
GO:0060562 epithelial tube morphogenesis
GO:0061146 Peyer's patch morphogenesis
GO:0061564 axon development
GO:0071229 cellular response to acid chemical
GO:0071300 cellular response to retinoic acid
GO:0071396 cellular response to lipid
GO:0071695 anatomical structure maturation
GO:0072001 renal system development
GO:0072006 nephron development
GO:0072073 kidney epithelium development
GO:0072163 mesonephric epithelium development
GO:0072164 mesonephric tubule development
GO:0072175 epithelial tube formation
GO:0072189 ureter development
GO:0072210 metanephric nephron development
GO:0072215 regulation of metanephros development
GO:0072216 positive regulation of metanephros development
GO:0072224 metanephric glomerulus development
GO:0072298 regulation of metanephric glomerulus development
GO:0072300 positive regulation of metanephric glomerulus development
GO:0072676 lymphocyte migration
GO:0090066 regulation of anatomical structure size
GO:0090183 regulation of kidney development
GO:0090184 positive regulation of kidney development
GO:0090192 regulation of glomerulus development
GO:0090193 positive regulation of glomerulus development
GO:0097021 lymphocyte migration into lymphoid organs
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097696 STAT cascade
GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules
GO:1903261 regulation of serine phosphorylation of STAT3 protein
GO:1903263 positive regulation of serine phosphorylation of STAT3 protein
GO:1903429 regulation of cell maturation
GO:1903431 positive regulation of cell maturation
GO:1904892 regulation of STAT cascade
GO:2000147 positive regulation of cell motility
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0019199 transmembrane receptor protein kinase activity
Cellular Component GO:0005769 early endosome
GO:0010008 endosome membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0043025 neuronal cell body
GO:0043235 receptor complex
GO:0044297 cell body
GO:0044440 endosomal part
GO:0045121 membrane raft
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa04144 Endocytosis
Reactome R-HSA-170984: ARMS-mediated activation
R-HSA-422475: Axon guidance
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-186763: Downstream signal transduction
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between RET and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between RET and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29631966adenocarcinomas; squamous Cell CarcinomaInhibit immunityThe receptor tyrosine kinase MET is implicated in malignant transformation, tumor progression, metastasis, and acquired treatment resistance.
27994058Thyroid Gland CarcinomaInhibit immunityConversely, RET/PTC3-expressing cells were characterized by a high IDO1 expression. These data provide the first evidence of a direct link between IDO1 expression and the oncogenic activation of RET in thyroid carcinoma and describe the involved signal transduction pathways.
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of RET in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of RET in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.2240.315
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1880.68
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2490.515
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0140.977
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0630.962
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1110.945
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2030.701
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.5820.457
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1760.833
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.0450.921
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4570.489
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1950.313
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of RET in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.11.49.70.0589
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.11.79.40.0895
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.511.8-2.31
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.718.2-10.50.576
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.112.5-1.41
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59022.2-22.20.505
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.97.40.51
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.17.71.41
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.27.1-0.91
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RET. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RET. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RET.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RET. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of RET expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between RET and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolRET
Nameret proto-oncogene
Aliases CDHF12; RET51; CDHR16; cadherin-related family member 16; RET receptor tyrosine kinase; rearranged during tr ......
Chromosomal Location10q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting RET collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting RET.
ID Name Drug Type Targets #Targets
DB00398SorafenibSmall MoleculeBRAF, FGFR1, FLT1, FLT3, FLT4, KDR, KIT, PDGFRB, RAF1, RET10
DB018091-Ter-Butyl-3-P-Tolyl-1h-Pyrazolo[3,4-D]Pyrimidin-4-YlamineSmall MoleculeHCK, RET2
DB05294VandetanibSmall MoleculeEGFR, PTK6, RET, TEK, VEGFA5
DB08875CabozantinibSmall MoleculeKDR, MET, RET3
DB08896RegorafenibSmall MoleculeABL1, BRAF, DDR2, EPHA2, FGFR1, FGFR2, FLT1, FLT4, FRK, KDR, KIT, ......18
DB08901PonatinibSmall MoleculeABL1, BCR, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, KDR, KIT, LCK, LYN, P ......15
DB12742AmuvatinibSmall MoleculeFLT3, KIT, MET, PDGFRA, RAD51, RET6