Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
Moldiag Diseases Genes Support Contact

MTOR gene

The MTOR gene encodes a phosphatidylinositol kinase-related kinases. This kinase is involved in cell signaling of apoptotic and immune regulation processes. Inhibitors are potent immunosuppressives. MINDS syndrome is caused by autosomal doinant mutations. Somatic mutations are responsible for isolated focal cortical dysplasia type 2 which manifests by intractable epilepsia. The ANGPTL7 gene is located in an intron of this gene.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Smith-Kingsmore syndrome
MTOR
Isolated focal cortical dysplasia type 2
MTOR
TSC1
TSC2

References:

1.

Cinà DP et al. (2012) Inhibition of MTOR disrupts autophagic flux in podocytes.

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2.

Bar-Peled L et al. (2013) A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.

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3.

Yang H et al. (2013) mTOR kinase structure, mechanism and regulation.

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4.

Robitaille AM et al. (2013) Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis.

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5.

Ben-Sahra I et al. (2013) Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1.

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6.

Efeyan A et al. (2013) Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival.

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7.

Fetalvero KM et al. (2013) Defective autophagy and mTORC1 signaling in myotubularin null mice.

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8.

Lee JH et al. (2012) De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly.

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9.

Yilmaz ÖH et al. (2012) mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake.

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10.

Thoreen CC et al. (2012) A unifying model for mTORC1-mediated regulation of mRNA translation.

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11.

Lamming DW et al. (2012) Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity.

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12.

Hsieh AC et al. (2012) The translational landscape of mTOR signalling steers cancer initiation and metastasis.

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13.

Zeng H et al. (2013) mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function.

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14.

Zoncu R et al. (2011) mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase.

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15.

Yu Y et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling.

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16.

Hsu PP et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling.

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17.

Lucanic M et al. (2011) N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans.

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18.

Narita M et al. (2011) Spatial coupling of mTOR and autophagy augments secretory phenotypes.

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19.

Jiao Y et al. (2011) DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.

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20.

Sengupta S et al. (2010) mTORC1 controls fasting-induced ketogenesis and its modulation by ageing.

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21.

Sathaliyawala T et al. (2010) Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling.

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22.

Li N et al. (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.

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23.

Yu L et al. (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR.

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24.

Dowling RJ et al. (2010) mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs.

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25.

Mroske C et al. (2015) Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities.

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26.

Terenzio M et al. (2018) Locally translated mTOR controls axonal local translation in nerve injury.

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27.

Gu X et al. (2017) {'i': ['S'], 'content': 'SAMTOR is an -adenosylmethionine sensor for the mTORC1 pathway.'}

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28.

Prouteau M et al. (2017) TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.

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29.

Di Malta C et al. (2017) Transcriptional activation of RagD GTPase controls mTORC1 and promotes cancer growth.

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30.

Castellano BM et al. (2017) Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex.

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31.

Møller RS et al. (2016) Germline and somatic mutations in the gene in focal cortical dysplasia and epilepsy.

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32.

Moosa S et al. (2017) Smith-Kingsmore syndrome: A third family with the MTOR mutation c.5395G>A p.(Glu1799Lys) and evidence for paternal gonadal mosaicism.

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33.

Mirzaa GM et al. (2016) Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism.

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34.

Chantranupong L et al. (2016) The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway.

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35.

Ben-Sahra I et al. (2016) mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle.

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36.

Aylett CH et al. (2016) Architecture of human mTOR complex 1.

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37.

Heublein S et al. (2010) Proton-assisted amino-acid transporters are conserved regulators of proliferation and amino-acid-dependent mTORC1 activation.

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38.

Schweitzer LD et al. (2015) Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1.

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39.

Nakashima M et al. (2015) Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb.

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40.

Leventer RJ et al. (2015) Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR.

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41.

Baynam G et al. (2015) A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces.

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42.

Lim JS et al. (2015) Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy.

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43.

Jewell JL et al. (2015) Metabolism. Differential regulation of mTORC1 by leucine and glutamine.

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44.

Wang S et al. (2015) Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1.

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45.

Rebsamen M et al. (2015) SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1.

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46.

Liang N et al. (2014) Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex.

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47.

Kye MJ et al. (2014) SMN regulates axonal local translation via miR-183/mTOR pathway.

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48.

Thedieck K et al. (2013) Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells.

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49.

Kim DH et al. (2002) mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.

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50.

Gangloff YG et al. (2004) Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development.

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51.

Jacinto E et al. (2004) Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive.

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52.

Hay N et al. (2004) Upstream and downstream of mTOR.

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53.

Scott RC et al. (2004) Role and regulation of starvation-induced autophagy in the Drosophila fat body.

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54.

Sarbassov DD et al. (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.

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55.

Murakami M et al. (2004) mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells.

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56.

Ravikumar B et al. (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.

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57.

Vellai T et al. (2003) Genetics: influence of TOR kinase on lifespan in C. elegans.

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58.

Kwon CH et al. (2003) mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo.

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59.

Kim DH et al. (2003) GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR.

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60.

Hara K et al. (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.

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61.

Brugarolas J et al. (2004) Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex.

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62.

Fingar DC et al. (2002) Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E.

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63.

Fang Y et al. (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling.

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64.

Dennis PB et al. (2001) Mammalian TOR: a homeostatic ATP sensor.

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65.

Castedo M et al. (2001) Human immunodeficiency virus 1 envelope glycoprotein complex-induced apoptosis involves mammalian target of rapamycin/FKBP12-rapamycin-associated protein-mediated p53 phosphorylation.

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66.

Onyango P et al. (1998) Molecular cloning and expression analysis of five novel genes in chromosome 1p36.

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67.

Lench NJ et al. (1997) The human gene encoding FKBP-rapamycin associated protein (FRAP) maps to chromosomal band 1p36.2.

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68.

Moore PA et al. (1996) Assignment of the human FKBP12-rapamycin-associated protein (FRAP) gene to chromosome 1p36 by fluorescence in situ hybridization.

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69.

Brown EJ et al. (1994) A mammalian protein targeted by G1-arresting rapamycin-receptor complex.

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70.

Sabatini DM et al. (1994) RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.

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71.

Zhang Y et al. (2014) Coordinated regulation of protein synthesis and degradation by mTORC1.

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72.

Raab-Graham KF et al. (2006) Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites.

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73.

None (2008) Rapamycin and tuberous sclerosis complex: from Easter Island to epilepsy.

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74.

Lee JH et al. (2010) Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies.

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75.

Rao RR et al. (2010) The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin.

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76.

Harrison DE et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.

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77.

Scott KL et al. (2009) GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer.

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78.

Araki K et al. (2009) mTOR regulates memory CD8 T-cell differentiation.

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79.

Delgoffe GM et al. (2009) The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.

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80.

Rosner M et al. (2009) Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle.

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81.

DiBella LM et al. (2009) Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway.

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82.

Park KK et al. (2008) Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway.

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83.

Mao JH et al. (2008) FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression.

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84.

Sancak Y et al. (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1.

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85.

Rodgers JT et al. (2014) mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert).

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86.

Cunningham JT et al. (2007) mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex.

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87.

Bai X et al. (2007) Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38.

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88.

Høyer-Hansen M et al. (2007) Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2.

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89.

Laviano A et al. (2006) Role of leucine in regulating food intake.

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90.

Bernardi R et al. (2006) PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR.

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91.

Li H et al. (2006) Nutrient regulates Tor1 nuclear localization and association with rDNA promoter.

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92.

Cota D et al. (2006) Hypothalamic mTOR signaling regulates food intake.

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93.

Holz MK et al. (2005) mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events.

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94.

Beuvink I et al. (2005) The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation.

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95.

Sarbassov DD et al. (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.

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