MTOR
Chr 1ADmechanistic target of rapamycin kinase
This serine/threonine protein kinase functions within two complexes (mTORC1 and mTORC2) that regulate cellular metabolism, growth, protein synthesis, and survival in response to nutrients and growth factors. Germline mutations cause Smith-Kingsmore syndrome through an autosomal dominant inheritance pattern, while somatic mutations lead to focal cortical dysplasia type II. The pathogenic mechanism involves loss of function, disrupting the normal regulation of cell growth and metabolic pathways critical for proper brain development.
Definitive — sufficient evidence for diagnostic panels
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MTOR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGDouble-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
NOT YET RECRUITINGTargeting Acute Myeloid Leukemia Immunosuppressive Microenvironment by combinedIDO1 Inhibition and PD-1 Blockade
RECRUITINGMos-FED (Mosaicism in Focal Epilepsy Cortical Dysplasia Tissue)
RECRUITINGRASopathy Biorepository
RECRUITINGSex-Speciffic Longevity Food Supplements
ACTIVE NOT RECRUITINGStudy of CT-01 as Monotherapy and Combination Therapy in Subjects With Intermediate or Advanced Hepatocellular Carcinoma
NOT YET RECRUITINGLAM-001 in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome.
RECRUITINGLinperlisib in the Treatment of aPRCA
NOT YET RECRUITINGFirst-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer
RECRUITINGPathogenesis of Chronic Kidney Disease Associated With Metabolic Dysfunction- Associated Fatty Liver Disease (MAFLD) and Treatment Response of Oral Semaglutide.
NOT YET RECRUITINGSapanisertib and Serabelisib (PIKTOR) With Paclitaxel and a Substudy With an Insulin-Suppressing Diet in Patients With Advanced/Recurrent Endometrial Cancer
RECRUITINGExternal Resources
Links to major genomics databases and tools