======= RET =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RET
  * **<color #00a2e8>Official Name</color>**: ret proto-oncogene
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5979|5979]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P07949|P07949]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RET&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RET|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/164761|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Cadherin|
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|posterior midgut development|
|Peyers patch morphogenesis|
|lymphocyte migration into lymphoid organs|
|ureter maturation|
|positive regulation of neuron maturation|
|positive regulation of metanephric glomerulus development|
|regulation of metanephric glomerulus development|
|mucosal-associated lymphoid tissue development|
|Peyers patch development|
|glial cell-derived neurotrophic factor receptor signaling pathway|
|plasma membrane protein complex|
|positive regulation of cell maturation|
|regulation of neuron maturation|
|positive regulation of cell size|
|positive regulation of glomerulus development|
|positive regulation of extrinsic apoptotic signaling pathway in absence of ligand|
|enteric nervous system development|
|midgut development|
|positive regulation of metanephros development|
|regulation of glomerulus development|
|ureter development|
|neuron cell-cell adhesion|
|positive regulation of peptidyl-serine phosphorylation of STAT protein|
|positive regulation of cell adhesion mediated by integrin|
|animal organ maturation|
|regulation of peptidyl-serine phosphorylation of STAT protein|
|regulation of metanephros development|
|regulation of cell maturation|
|innervation|
|response to pain|
|membrane protein proteolysis|
|neuron maturation|
|positive regulation of kidney development|
|autonomic nervous system development|
|regulation of cell adhesion mediated by integrin|
|regulation of extrinsic apoptotic signaling pathway in absence of ligand|
|positive regulation of extrinsic apoptotic signaling pathway|
|neural crest cell migration|
|regulation of kidney development|
|transmembrane receptor protein tyrosine kinase activity|
|lymphocyte migration|
|multicellular organismal response to stress|
|cellular response to retinoic acid|
|neural crest cell development|
|nerve development|
|stem cell development|
|metanephros development|
|mesenchymal cell development|
|ureteric bud development|
|mesonephric epithelium development|
|mesonephric tubule development|
|protein tyrosine kinase activity|
|neural crest cell differentiation|
|mesonephros development|
|positive regulation of peptidyl-serine phosphorylation|
|response to retinoic acid|
|embryonic epithelial tube formation|
|kidney epithelium development|
|regulation of receptor signaling pathway via JAK-STAT|
|digestive tract development|
|epithelial tube formation|
|regulation of receptor signaling pathway via STAT|
|anatomical structure maturation|
|regulation of peptidyl-serine phosphorylation|
|retina development in camera-type eye|
|digestive system development|
|peptidyl-tyrosine phosphorylation|
|morphogenesis of embryonic epithelium|
|peptidyl-tyrosine modification|
|tube formation|
|regulation of extrinsic apoptotic signaling pathway|
|activation of MAPK activity|
|mesenchymal cell differentiation|
|cell maturation|
|stem cell differentiation|
|positive regulation of protein kinase B signaling|
|homophilic cell adhesion via plasma membrane adhesion molecules|
|ameboidal-type cell migration|
|positive regulation of apoptotic signaling pathway|
|regulation of cell size|
|regulation of axonogenesis|
|signaling receptor activity|
|receptor complex|
|cellular response to acid chemical|
|endosome membrane|
|regulation of protein kinase B signaling|
|mesenchyme development|
|membrane raft|
|developmental maturation|
|early endosome|
|cell-cell adhesion via plasma-membrane adhesion molecules|
|axon guidance|
|positive regulation of MAP kinase activity|
|neuron projection guidance|
|kidney development|
|positive regulation of neuron projection development|
|renal system development|
|axon|
|regulation of cell morphogenesis involved in differentiation|
|epithelial tube morphogenesis|
|camera-type eye development|
|urogenital system development|
|activation of protein kinase activity|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|response to acid chemical|
|eye development|
|visual system development|
|sensory system development|
|positive regulation of neuron differentiation|
|MAPK cascade|
|axonogenesis|
|neuronal cell body|
|regulation of cellular component size|
|leukocyte migration|
|positive regulation of cell projection organization|
|signal transduction by protein phosphorylation|
|regulation of apoptotic signaling pathway|
|positive regulation of cell adhesion|
|axon development|
|dendrite|
|morphogenesis of an epithelium|
|cell morphogenesis involved in neuron differentiation|
|positive regulation of neurogenesis|
|neuron projection morphogenesis|
|plasma membrane bounded cell projection morphogenesis|
|regulation of cell morphogenesis|
|cell projection morphogenesis|
|regulation of neuron projection development|
|positive regulation of cell migration|
|cell-cell adhesion|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of anatomical structure size|
|cell part morphogenesis|
|regulation of protein serine/threonine kinase activity|
|cellular response to lipid|
|positive regulation of cell motility|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cellular component movement|
|positive regulation of cell development|
|positive regulation of MAPK cascade|
|sensory organ development|
|chemotaxis|
|taxis|
|positive regulation of locomotion|
|cell morphogenesis involved in differentiation|
|tissue morphogenesis|
|embryonic morphogenesis|
|positive regulation of kinase activity|
|hematopoietic or lymphoid organ development|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|immune system development|
|tube morphogenesis|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|neuron projection development|
|regulation of cell adhesion|
|intracellular membrane-bounded organelle|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|regulation of cell projection organization|
|enzyme linked receptor protein signaling pathway|
|calcium ion binding|
|cell morphogenesis|
|regulation of MAPK cascade|
|regulation of protein kinase activity|
|neuron development|
|regulation of neurogenesis|
|cellular component morphogenesis|
|tube development|
|regulation of cell migration|
|response to lipid|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|regulation of cell motility|
|regulation of nervous system development|
|cell adhesion|
|regulation of cell development|
|biological adhesion|
|cell migration|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|embryo development|
|regulation of locomotion|
|regulation of cellular component movement|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|cell motility|
|localization of cell|
|epithelium development|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|cell projection organization|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|proteolysis|
|phosphorylation|
|locomotion|
|positive regulation of developmental process|
|integral component of plasma membrane|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|cell development|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp71|KU-0063794 3.8μM R02 exp71]]|-1.86|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 17344
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -4.01 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RET Expression in NALM6 Cells: -4.01'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>