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RET

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].

Name	OMIM ID	Ensembl ID	HGNC ID	PHARMGKB ID	Map Location
ret proto-oncogene	MIM:164761	Ensembl:ENSG00000165731	HGNC:HGNC:9967	PA34335	10q11.21

Gene Categories:

DRUGGABLE GENOME TYROSINE KINASE DRUG RESISTANCE KINASE CLINICALLY ACTIONABLE

GO terms in RET

Term Type	Evidence Type	GO Term ID	GO Des.
BP	TAS	GO:0000165	MAPK cascade
BP	IMP	GO:0000187	activation of MAPK activity
BP	IEA	GO:0001657	ureteric bud development
BP	IEA	GO:0001755	neural crest cell migration
BP	IEA	GO:0001838	embryonic epithelial tube formation
BP	TAS	GO:0006468	protein phosphorylation
BP	IEA	GO:0007156	homophilic cell adhesion via plasma membrane adhesion molecules
BP	IMP	GO:0007158	neuron cell-cell adhesion
BP	TAS	GO:0007165	signal transduction
BP	IBA	GO:0007275	multicellular organism development
BP	TAS	GO:0007411	axon guidance
BP	TAS	GO:0007497	posterior midgut development
BP	IBA	GO:0009968	negative regulation of signal transduction
BP	IMP	GO:0010976	positive regulation of neuron projection development
BP	IEA	GO:0014042	positive regulation of neuron maturation
BP	IEA	GO:0018108	peptidyl-tyrosine phosphorylation
BP	IBA	GO:0030154	cell differentiation
BP	IDA	GO:0030155	regulation of cell adhesion
BP	IDA	GO:0030335	positive regulation of cell migration
BP	IEA	GO:0033141	positive regulation of peptidyl-serine phosphorylation of STAT protein
BP	IDA	GO:0033619	membrane protein proteolysis
BP	IDA	GO:0033630	positive regulation of cell adhesion mediated by integrin
BP	IBA	GO:0033674	positive regulation of kinase activity
BP	IEA	GO:0035799	ureter maturation
BP	IDA	GO:0035860	glial cell-derived neurotrophic factor receptor signaling pathway
BP	IEA	GO:0042493	response to drug
BP	IEA	GO:0042551	neuron maturation
BP	IBA	GO:0043066	negative regulation of apoptotic process
BP	IDA	GO:0043410	positive regulation of MAPK cascade
BP	IEA	GO:0045793	positive regulation of cell size
BP	ISS	GO:0045893	positive regulation of transcription, DNA-templated
BP	ISS	GO:0048265	response to pain
BP	IEA	GO:0048484	enteric nervous system development
BP	IEA	GO:0050770	regulation of axonogenesis
BP	IMP	GO:0051897	positive regulation of protein kinase B signaling
BP	IEA	GO:0060041	retina development in camera-type eye
BP	IEA	GO:0060384	innervation
BP	ISS	GO:0061146	Peyer's patch morphogenesis
BP	IBA	GO:0070374	positive regulation of ERK1 and ERK2 cascade
BP	IMP	GO:0071300	cellular response to retinoic acid
BP	ISS	GO:0072300	positive regulation of metanephric glomerulus development
BP	ISS	GO:0097021	lymphocyte migration into lymphoid organs
BP	TAS	GO:2001241	positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
CC	IBA	GO:0005737	cytoplasm
CC	IEA	GO:0005769	early endosome
CC	IDA	GO:0005829	cytosol
CC	IDA	GO:0005886	plasma membrane
CC	TAS	GO:0005886	plasma membrane
CC	IBA	GO:0005887	integral component of plasma membrane
CC	IDA	GO:0005887	integral component of plasma membrane
CC	IDA	GO:0010008	endosome membrane
CC	IBA	GO:0030424	axon
CC	IEA	GO:0030424	axon
CC	IEA	GO:0030425	dendrite
CC	IEA	GO:0043025	neuronal cell body
CC	IDA	GO:0043231	intracellular membrane-bounded organelle
CC	IBA	GO:0043235	receptor complex
CC	IDA	GO:0043235	receptor complex
CC	IEA	GO:0045121	membrane raft
CC	IDA	GO:0098797	plasma membrane protein complex
MF	IBA	GO:0004709	MAP kinase kinase kinase activity
MF	IBA	GO:0004713	protein tyrosine kinase activity
MF	TAS	GO:0004713	protein tyrosine kinase activity
MF	IBA	GO:0004714	transmembrane receptor protein tyrosine kinase activity
MF	IDA	GO:0004714	transmembrane receptor protein tyrosine kinase activity
MF	TAS	GO:0004714	transmembrane receptor protein tyrosine kinase activity
MF	IBA	GO:0004888	transmembrane signaling receptor activity
MF	TAS	GO:0005088	Ras guanyl-nucleotide exchange factor activity
MF	IDA	GO:0005509	calcium ion binding
MF	IPI	GO:0005515	protein binding
MF	IEA	GO:0005524	ATP binding
MF	IBA	GO:0031434	mitogen-activated protein kinase kinase binding
MF	TAS	GO:0038023	signaling receptor activity

Gene expression in normal tissue: RET

Select Project:

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in RET

Database	Pathway ID	Pathway Des.
reactome	R-HSA-1266738	Developmental Biology
reactome	R-HSA-162582	Signal Transduction
reactome	R-HSA-422475	Axon guidance
reactome	R-HSA-5673001	RAF/MAP kinase cascade
reactome	R-HSA-5683057	MAPK family signaling cascades
reactome	R-HSA-5684996	MAPK1/MAPK3 signaling
reactome	R-HSA-8853659	RET signaling
pid	ajdiss_2pathway	Posttranslational regulation of adherens junction stability and dissassembly
pid	ret_pathway	Signaling events regulated by Ret tyrosine kinase
kegg	hsa05200	Pathways in cancer - Homo sapiens (human)
kegg	hsa05216	Thyroid cancer - Homo sapiens (human)
kegg	hsa05230	Central carbon metabolism in cancer - Homo sapiens (human)
pharmgkb	PA165959425	Pathway_PA165959425
pharmgkb	PA165959584	Sorafenib Pharmacodynamics
wikipathways	WP2586	Aryl Hydrocarbon Receptor
wikipathways	WP2855	Dopaminergic Neurogenesis
wikipathways	WP706	Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways

Gene-Drug: Aster Plot

Drug ID	Drug Name	Model Num.
iGMDRD999	RET inhibitor	4
iGMDRD116	CD437	3
iGMDRD770	Hydroxy Vandetanib	1
iGMDRD512	nutlin 3	4
iGMDRD330	BRD4132	3
iGMDRD307	Manumycin A	6
iGMDRD945	ML214	3
iGMDRD132	(-)-gallocatechin-3-O-gallate	4
iGMDRD240	Vandetanib	10
iGMDRD499	PDMP	6
iGMDRD85	Ursolic acid	3
iGMDRD341	Triacsin c	1
iGMDRD267	Oligomycin A	1
iGMDRD415	LE-135	3
iGMDRD434	BMS-536924	2
iGMDRD241	Sunitinib	3
iGMDRD289	Parthenolide	3
iGMDRD221	Tamoxifen	3
iGMDRD467	Motesanib	2
iGMDRD5	Tyrphostin AG 1478	3
iGMDRD137	Indisulam	2
iGMDRD158	NSC141540	3
iGMDRD271	Brefeldin A	3
iGMDRD202	Curcumin	3
iGMDRD82	Quiflapon	6
iGMDRD300	Tozasertib	6
iGMDRD872	BRD7137	3
iGMDRD882	CIL41	3
iGMDRD286	Nsc 632839	3
iGMDRD871	BRD6368	3
iGMDRD427	ABT737	2
iGMDRD144	NSC95397	2
iGMDRD772	BRD4770	6
iGMDRD889	Compound 7d-cis	3
iGMDRD599	Salermide	6
iGMDRD571	Cabozantinib	2
iGMDRD502	AZD1480	1
iGMDRD126	Tipifarnib	2
iGMDRD280	CYTOCHALASIN B	3
iGMDRD52	Rotenone	3
iGMDRD187	BRD9876	3
iGMDRD885	Compound 110	3
iGMDRD441	TW 37	3
iGMDRD318	PAC-1	3
iGMDRD782	DC-45-A2	4
iGMDRD171	Pemetrexed	6
iGMDRD134	Sorafenib	1
iGMDRD138	PX 12	3
iGMDRD474	Avrainvillamide	3
iGMDRD270	Ciclosporin	1
iGMDRD524	ISX-9	3
iGMDRD690	PRIMA-1MET	3
iGMDRD780	PP-30	3
iGMDRD887	Compound 23 citrate	1
iGMDRD188	Piperlongumine	1

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in RET

SITE

DATATYPES

CLASSFICATION

Disclaimer: iGMDR is intended for research purposes only. Its information cannot be used for emergencies or medical or professional advice.