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GeneE
50 sources retrieved ยท Most recent: April 2026 ยท Index updated 14 days ago
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MTOR
mechanistic target of rapamycin kinase
Chromosome 1 ยท 1p36.22
NCBI Gene: 2475Ensembl: ENSG00000198793.14HGNC: HGNC:3942UniProt: A0A8V8TQ52
2,567PubMed Papers
22Diseases
26Drugs
53Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneKinase
RESEARCH IMPACT
Highly StudiedVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
โœ“ Experimental GO Evidenceโœ“ Swiss-Prot Reviewed
cellular response to amino acid stimulusTORC2 signalingpositive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic processpositive regulation of keratinocyte migrationMacrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndromeisolated focal cortical dysplasia type IIovergrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genesneurodegenerative disease
โœฆAI Summary

MTOR (mechanistic target of rapamycin kinase) is a serine/threonine protein kinase that functions as a master regulator of cellular metabolism, growth, and survival 1. It integrates diverse environmental signals including nutrients, hormones, growth factors, and energy status to control fundamental cellular processes 2. MTOR operates within two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1, activated by amino acids and growth factors at the lysosome membrane, promotes protein, lipid, and nucleotide synthesis by phosphorylating translation regulators including EIF4EBP1 and RPS6KB1 3. It also inhibits catabolic pathways by suppressing autophagy through ULK1 phosphorylation 1. In contrast, mTORC2 is nutrient-insensitive and transduces growth factor signals to regulate cell proliferation and cytoskeletal organization by phosphorylating AGC kinases including AKT and PKC 2. Dysregulation of mTOR signaling is implicated in multiple human diseases including metabolic disorders, cancer, and aging 2. Notably, genetic mutations in MTOR cause Smith-Kingsmore syndrome and focal cortical dysplasia, demonstrating its critical role in neural development 4. Given its extensive biological impact, mTOR represents a major therapeutic target, with mTOR inhibitors showing clinical benefit across various disease contexts 5.

Sources cited
1
mTOR is a master regulator of cellular metabolism and plays a crucial role in autophagy regulation
PMID: 25654547
2
mTOR integrates environmental signals to control protein synthesis, cell growth, survival, and apoptosis; dysregulation is implicated in metabolic diseases, cancer, and aging
PMID: 38892329
3
mTOR is activated by amino acids, insulin, and growth factors; regulates protein synthesis components including initiation/elongation factors and ribosome biogenesis
PMID: 16990457
4
mTOR signaling impacts cortical neurogenesis and is relevant to neural development
PMID: 36334595
5
mTOR signaling regulates amino acid, glucose, nucleotide, and lipid metabolism in cancer cells; mTOR inhibitors have therapeutic applications
PMID: 30425336
Disease Associationsโ“˜22
Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndromeOpen Targets
0.83Strong
isolated focal cortical dysplasia type IIOpen Targets
0.82Strong
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genesOpen Targets
0.69Moderate
neurodegenerative diseaseOpen Targets
0.56Moderate
CEBALID syndromeOpen Targets
0.52Moderate
clear cell renal carcinomaOpen Targets
0.52Moderate
Intellectual disabilityOpen Targets
0.51Moderate
genetic disorderOpen Targets
0.51Moderate
Alzheimer diseaseOpen Targets
0.49Moderate
Parkinson diseaseOpen Targets
0.49Moderate
lysosomal storage diseaseOpen Targets
0.47Moderate
multiple sclerosisOpen Targets
0.47Moderate
renal cell carcinomaOpen Targets
0.46Moderate
neoplasmOpen Targets
0.44Moderate
colorectal adenocarcinomaOpen Targets
0.43Moderate
papillary renal cell carcinomaOpen Targets
0.41Moderate
Merkel cell skin cancerOpen Targets
0.40Weak
skin basal cell carcinomaOpen Targets
0.39Weak
cardiovascular diseaseOpen Targets
0.38Weak
skin squamous cell carcinomaOpen Targets
0.38Weak
Focal cortical dysplasia 2UniProt
Smith-Kingsmore syndromeUniProt
Pathogenic Variants53
NM_004958.4(MTOR):c.4468T>C (p.Trp1490Arg)Likely pathogenic
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜…โ˜†2025โ†’ Residue 1490
NM_004958.4(MTOR):c.5005G>T (p.Ala1669Ser)Likely pathogenic
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜…โ˜†2025โ†’ Residue 1669
NM_004958.4(MTOR):c.5930C>G (p.Thr1977Arg)Pathogenic
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 1977
NM_004958.4(MTOR):c.4448G>A (p.Cys1483Tyr)Pathogenic
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|CEBALID syndrome|not provided|Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 1483
NM_004958.4(MTOR):c.6644C>A (p.Ser2215Tyr)Pathogenic
Isolated focal cortical dysplasia type II|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 2215
NM_004958.4(MTOR):c.7280T>C (p.Leu2427Pro)Pathogenic
Isolated focal cortical dysplasia type II|CEBALID syndrome|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 2427
NM_004958.4(MTOR):c.5930C>A (p.Thr1977Lys)Pathogenic
not provided|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome|Isolated focal cortical dysplasia type II
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 1977
NM_004958.4(MTOR):c.6644C>T (p.Ser2215Phe)Pathogenic
not provided|Isolated focal cortical dysplasia type II|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 2215
NM_004958.4(MTOR):c.4447T>C (p.Cys1483Arg)Pathogenic
Hemimegalencephaly|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 1483
NM_004958.4(MTOR):c.4379T>C (p.Leu1460Pro)Pathogenic
Isolated focal cortical dysplasia type II|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜…โ˜†2022โ†’ Residue 1460
NM_004958.4(MTOR):c.5395G>A (p.Glu1799Lys)Pathogenic
Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome|not provided|Inborn genetic diseases|Severe intellectual disability|CEBALID syndrome|Rare genetic intellectual disability|Isolated focal cortical dysplasia type II|Intellectual disability|Isolated focal cortical dysplasia type II;Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
โ˜…โ˜…โ˜†โ˜†2026โ†’ Residue 1799
NM_004958.4(MTOR):c.5663T>G (p.Phe1888Cys)Pathogenic
Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome|not provided
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 1888
NM_004958.4(MTOR):c.7216G>A (p.Val2406Met)Pathogenic
Macrocephaly|not provided|Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 2406
NM_004958.4(MTOR):c.5930C>T (p.Thr1977Ile)Pathogenic
MTOR-related megalencephaly and pigmentary mosaicism in skin|Isolated focal cortical dysplasia type II|CEBALID syndrome|not provided|MTOR-related disorder|Isolated focal cortical dysplasia type II;Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 1977
NM_004958.4(MTOR):c.7255G>A (p.Glu2419Lys)Pathogenic
not provided|CEBALID syndrome|Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|Inborn genetic diseases
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 2419
NM_004958.4(MTOR):c.5662T>C (p.Phe1888Leu)Likely pathogenic
Overgrowth syndrome|Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome|Neoplasm
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 1888
NM_004958.4(MTOR):c.6981G>A (p.Met2327Ile)Pathogenic
Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome|not provided
โ˜…โ˜…โ˜†โ˜†2023โ†’ Residue 2327
NM_004958.4(MTOR):c.7238G>T (p.Ser2413Ile)Pathogenic
Inborn genetic diseases|CEBALID syndrome|Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
โ˜…โ˜…โ˜†โ˜†2023โ†’ Residue 2413
NM_004958.4(MTOR):c.5380G>A (p.Ala1794Thr)Likely pathogenic
not provided
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 1794
NM_004958.4(MTOR):c.6306C>A (p.Asp2102Glu)Likely pathogenic
MTOR-related disorder
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 2102
View on ClinVar โ†—
Drug Targets26
APITOLISIBPhase II
PI3-kinase class I inhibitor
non-Hodgkins lymphoma
AZD-8055Phase I/II
Serine/threonine-protein kinase mTOR inhibitor
BGT-226Phase I/II
PI3-kinase class I inhibitor
CC-115Phase I
DNA-dependent protein kinase inhibitor
multiple myeloma
DACTOLISIBPhase III
PI3-kinase class I inhibitor
Respiratory tract infection
DS-3078APhase I
Serine/threonine-protein kinase mTOR inhibitor
DS-7423Phase I
Serine/threonine-protein kinase mTOR inhibitor
GEDATOLISIBPhase III
PI3-kinase class I inhibitor
breast cancer
INDOXIMODPhase II/III
mTORC1 activator
melanoma
OMIPALISIBPhase I
PI3-kinase class I inhibitor
lymphoma
ONATASERTIBPhase II
Serine/threonine-protein kinase mTOR inhibitor
hepatocellular carcinoma
OSI-027Phase II
Serine/threonine-protein kinase mTOR inhibitor
renal cell carcinoma
PALOMID-529Phase I
Serine/threonine-protein kinase mTOR inhibitor
Alzheimer disease
PANULISIBPhase I
PI3-kinase class I inhibitor
PERHEXILINEApproved
Carnitine O-palmitoyltransferase 1, muscle isoform inhibitor
cardiovascular disease
PERHEXILINE MALEATEUNKNOWN
Carnitine O-palmitoyltransferase 1, muscle isoform inhibitor
PF-04691502Phase II
PI3-kinase class I inhibitor
endometrial cancer
PKI-179Phase I
PI3-kinase p110-alpha subunit inhibitor
neoplasm
RG-7603Phase I
Serine/threonine-protein kinase mTOR inhibitor
non-Hodgkins lymphoma
RIDAFOROLIMUSApproved
Serine/threonine-protein kinase mTOR inhibitor
neoplasm
SAMOTOLISIBPhase II
PI3-kinase class I inhibitor
prostate cancer
SAPANISERTIBPhase II
Serine/threonine-protein kinase mTOR inhibitor
breast cancer
SF-1126Phase II
PI3-kinase class I inhibitor
head and neck malignant neoplasia
VISTUSERTIBPhase II
Serine/threonine-protein kinase mTOR inhibitor
VOXTALISIBPhase II
Serine/threonine-protein kinase mTOR inhibitor
VS-5584Phase I
Serine/threonine-protein kinase mTOR inhibitor
Malignant Mesothelioma
Related Genes
EIF4BProtein interaction100%EIF4EProtein interaction100%EIF4EBP2Protein interaction100%ULK2Protein interaction100%ULK1Protein interaction100%ATG101Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
98%
Liver
81%
Bone Marrow
74%
Lung
62%
Ovary
52%
Gene Interaction Network
Click a node to explore
MTOREIF4BEIF4EEIF4EBP2ULK2ULK1ATG101
PROTEIN STRUCTURE
Preparing viewerโ€ฆ
PDB4DRI ยท 1.45 ร… ยท X-ray
View on RCSB โ†—
Constraintโ“˜
LOEUFโ“˜
0.27Highly Constrained
pLIโ“˜
1.00Intolerant
Observed/Expected LoF0.22 [0.18โ€“0.27]
RankingsWhere MTOR stands among ~20K protein-coding genes
  • #32of 20,598
    Most Researched2,567 ยท top 1%
  • #489of 1,025
    FDA-Approved Drug Targets2
  • #1,270of 5,498
    Most Pathogenic Variants53 ยท top quartile
  • #894of 17,882
    Most Constrained (LOEUF)0.27 ยท top 5%
Genes detectedMTOR
Sources retrieved50 papers
Response timeโ€”
๐Ÿ“„ Sources
50โ–ผ
1
mTOR: a pharmacologic target for autophagy regulation.
PMID: 25654547
J Clin Invest ยท 2015
1.00
2
mTOR signalling and cellular metabolism are mutual determinants in cancer.
PMID: 30425336
Nat Rev Cancer ยท 2018
0.90
3
Immunosuppression.
PMID: 23095440
Curr Opin Organ Transplant ยท 2012
0.82
4
The mTOR pathway in the control of protein synthesis.
PMID: 16990457
Physiology (Bethesda) ยท 2006
0.80
5
mTOR, translational control and human disease.
PMID: 15659337
Semin Cell Dev Biol ยท 2005
0.78