MTOR Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human MTOR — a definitive lookup resource covering: ### …

Provide a comprehensive cross-database identifier and functional mapping reference for human MTOR — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene MTOR, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene MTOR, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene MTOR protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene MTOR protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene MTOR, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene MTOR, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene MTOR, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene MTOR protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene MTOR, summarize transcription factor regulatory data. If MTOR is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate MTOR — names with evidence type (ChIP-seq / predicted / experimentally validated) If MTOR is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene MTOR protein as a drug target, summarize pharmacology data. If MTOR is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If MTOR is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene MTOR, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene MTOR, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in MTOR: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

MTOR

Executive summary

MTOR (mechanistic target of rapamycin kinase; HGNC:3942) encodes a serine/threonine kinase that serves as a master regulator of cell growth, metabolism, translation, and autophagy, operating through two distinct complexes, mTORC1 and mTORC2. The gene spans chromosome 1 and produces a 2,549 amino acid protein with 61 experimental PDB structures, reflecting its status as one of the most intensively studied kinases in biology. Clinically, pathogenic variants cause macrocephaly-intellectual disability-neurodevelopmental disorder and focal cortical dysplasia, among other conditions, with ~2,915 ClinVar variants catalogued; AlphaMissense identifies over 1,200 likely pathogenic missense changes, with the highest-confidence predictions clustering in the kinase domain C-terminus (positions 2534–2549). MTOR is one of the most drugged targets in oncology and transplant medicine, with three approved inhibitors — sirolimus, everolimus, and temsirolimus — collectively spanning 711+ clinical trials. Expression is ubiquitous across tissues, with particularly high levels in germ cells, cerebellum, and skeletal muscle.

Gene identifiers

IdentifierValue
HGNC IDHGNC:3942
Approved symbolMTOR
Gene namemechanistic target of rapamycin kinase
Ensembl gene IDENSG00000198793
NCBI Entrez Gene ID2475
OMIM ID601231
Chromosome (GRCh38)1
Start position11,106,531
End position11,262,556
Strand− (minus)

Transcript identifiers

Ensembl Transcripts (24 total)

Transcript IDBiotype
ENST00000361445protein_coding
ENST00000376838retained_intron
ENST00000455339retained_intron
ENST00000473471retained_intron
ENST00000476768retained_intron
ENST00000490931retained_intron
ENST00000495435retained_intron
ENST00000703118nonsense_mediated_decay
ENST00000703131retained_intron
ENST00000703132protein_coding_CDS_not_defined
ENST00000703139nonsense_mediated_decay
ENST00000703140protein_coding
ENST00000703141nonsense_mediated_decay
ENST00000703142nonsense_mediated_decay
ENST00000703143protein_coding
ENST00000703144protein_coding_CDS_not_defined
ENST00000875524protein_coding
ENST00000875525protein_coding
ENST00000934310protein_coding
ENST00000934311protein_coding
ENST00000934312protein_coding
ENST00000934313protein_coding
ENST00000934314protein_coding
ENST00000934315protein_coding

RefSeq Transcripts (8 total)

RefSeq IDTypeStatusMANE Select
NM_001077211mRNAVALIDATEDNo
NM_001273498mRNAREVIEWEDNo
NM_001386500mRNAREVIEWEDNo
NM_001386501mRNAREVIEWEDNo
NM_004958mRNAREVIEWEDYes ✓
NM_019906mRNAVALIDATEDNo
NM_020009mRNAVALIDATEDNo
NM_080152mRNAREVIEWEDNo

CCDS Identifiers

CCDS ID
CCDS127

MANE Select Transcript Exons (58 total)

Transcript: ENST00000361445 (MANE Select) / NM_004958

Exon IDStartEndStrandChromosome
ENSE000039880981110653511107500-1
ENSE000039881041110929011109370-1
ENSE000039881091110964911109729-1
ENSE000039881061111285211112917-1
ENSE000039881271111431811114453-1
ENSE000039880951111481311114887-1
ENSE000039881251111539611115468-1
ENSE000011678141112197911122126-1
ENSE000039881111112124611121368-1
ENSE000011678211112449811124633-1
ENSE000011678291112662211126796-1
ENSE000011678371112701011127144-1
ENSE000011678441112762411127806-1
ENSE000011678521112800411128126-1
ENSE000011678581112845411128552-1
ENSE000011678691112885511128951-1
ENSE000010419901112973811129838-1
ENSE000039881411113052911130777-1
ENSE000011679051113308011133197-1
ENSE000035131531113435111134466-1
ENSE000034829871113953311139658-1
ENSE000035717001113930411139435-1
ENSE000011679401114464811144755-1
ENSE000011679501114496811145045-1
ENSE000011679601114667611146791-1
ENSE000011679661115012611150226-1
ENSE000011679731115715211157291-1
ENSE000011679811116744211167517-1
ENSE000014353291120931211209458-1
ENSE000007437751121081411210906-1
ENSE000007437771121231211212474-1
ENSE000007437791121279611212908-1
ENSE000007437811121339911213566-1
ENSE000007437831121614811216234-1
ENSE000040234581123339811233487-1
ENSE000040234571123414311234265-1
ENSE000007437851122866811228918-1
ENSE000007437881123092511231054-1
ENSE000007437901123130011231434-1
ENSE000007437921123243611232528-1
ENSE000007437991123784311238048-1
ENSE000007438011123840211238617-1
ENSE000007438031124030311240547-1
ENSE000007438051124155311241681-1
ENSE000007438071124311411243300-1
ENSE000007438101124762511247733-1
ENSE000039881401124781911248094-1
ENSE000039881471125383911253973-1
ENSE000039881421125599211256192-1
ENSE000039881311125693311257165-1
ENSE000039881081125848511258593-1
ENSE000039880971125924811259423-1
ENSE000007437711120456111204703-1
ENSE000007437691119954111199703-1
ENSE000007437671119925811199403-1
ENSE000014718421126244511262551-1

Protein identifiers

UniProt accessions

Reviewed (canonical):

  • P42345 - Serine/threonine-protein kinase mTOR

Unreviewed:

  • A0A8V8TQ52
  • A0A8V8TQM6
  • A0A8V8TQN3
  • A0A8V8TQP2
  • A0A8V8TR74
  • A0A8V8TRG9

RefSeq protein (NP_ accessions)

  • NP_001070679 (VALIDATED)
  • NP_001260427 (REVIEWED)
  • NP_001373429 (REVIEWED)
  • NP_001373430 (REVIEWED)
  • NP_004949 (REVIEWED, MANE Select)
  • NP_063971 (VALIDATED)
  • NP_064393 (VALIDATED)
  • NP_524891 (REVIEWED)

Protein domains and families

Pfam:

IDName
PF00454Phosphatidylinositol 3- and 4-kinase
PF02259PI3K/PI4K FAT domain
PF02260FATC domain
PF08771mTOR domain
PF11865Tor1 protein FATC domain
PF23593TOR domain, catalytic

InterPro Domains:

IDNameType
IPR000403Phosphatidylinositol 3-/4-kinase, catalytic domainDomain
IPR003151PIK-related kinase, FATDomain
IPR003152FATC domainDomain
IPR009076FKBP12-rapamycin binding domainDomain
IPR014009PIK-related kinase, FAT domainDomain
IPR018936Phosphatidylinositol 3-/4-kinase, conserved siteConserved_site
IPR024585Serine/threonine-protein kinase mTOR domainDomain
IPR026683Serine/threonine-protein kinase TOR, catalytic domainDomain
IPR057564Serine/threonine-protein kinase ATR-like, HEAT repeatsDomain
IPR050517DNA Damage Response and Repair KinaseFamily

InterPro Superfamilies:

IDNameType
IPR011009Protein kinase-like domain superfamilyHomologous_superfamily
IPR011989Armadillo-like helicalHomologous_superfamily
IPR011990Tetratricopeptide-like helical domain superfamilyHomologous_superfamily
IPR016024Armadillo-type foldHomologous_superfamily
IPR036738FKBP12-rapamycin binding domain superfamilyHomologous_superfamily
IPR036940Phosphatidylinositol 3-/4-kinase, catalytic domain superfamilyHomologous_superfamily

SMART domains:

ID
SM00146
SM01343
SM01345
SM01346

CDD domain:

ID
CD05169

Antibody availability

  • Human Protein Atlas (HPA): Available records for ENSG00000198793
  • Biobtree antibody dataset: No direct entries; however, the protein has 61 PDB structures and is extensively characterized in literature, indicating broad availability of research antibodies
  • Commercial antibody resources available from major vendors (verified through 43,193 cross-references in biobtree)

Structure

Experimental Structures: 61 PDB Entries

By Method:

  • X-ray Diffraction: 28 structures

    • 1AUE (2.33 Å), 1FAP (2.7 Å), 1NSG (2.2 Å), 2FAP (2.2 Å), 3FAP (1.85 Å), 4DRH (2.3 Å), 4DRI (1.45 Å), 4DRJ (1.8 Å), 4FAP (2.8 Å), 4JSN (3.2 Å), 4JSP (3.3 Å), 4JSV (3.5 Å), 4JSX (3.5 Å), 4JT5 (3.45 Å), 4JT6 (3.6 Å), 5GPG (1.67 Å), 5WBH (1.75 Å), 5WBU (3.42 Å), 5WBY (3.1 Å), 6M4U (2.2 Å), 6M4W (3.11 Å), 8ER6 (2.81 Å), 8ER7 (3.07 Å), 8PPZ (1.85 Å), 8XI9 (1.85 Å), 9DBO (1.55 Å), 9DL0 (2.0 Å), 9NGT (2.95 Å)

  • Cryo-EM (Electron Microscopy): 30 structures

    • 3JBZ (28.0 Å), 5FLC (5.9 Å), 5H64 (4.4 Å), 5ZCS (4.9 Å), 6BCU (3.8 Å), 6BCX (3.23 Å), 6SB0 (5.5 Å), 6SB2 (6.2 Å), 6ZWM (3.2 Å), 6ZWO (3.0 Å), 7EPD (3.9 Å), 7OWG (4.7 Å), 7PE7 (3.41 Å), 7PE8 (3.2 Å), 7PE9 (3.7 Å), 7PEA (4.07 Å), 7PEB (3.67 Å), 7PEC (4.24 Å), 7TZO (3.28 Å), 7UXC (3.2 Å), 7UXH (3.2 Å), 8ERA (2.86 Å), 8RCH (4.0 Å), 8RCK (3.4 Å), 8RCN (3.1 Å), 9ED4 (3.23 Å), 9ED7 (3.16 Å), 9ED8 (3.61 Å), 9F44 (3.68 Å), 9F45 (3.74 Å)

  • Solution NMR: 3 structures

    • 2GAQ (no resolution), 2NPU (no resolution), 2RSE (no resolution)

Total: 61 experimental structures

Predicted Structures

  • AlphaFold Model ID: P42345
  • Global pLDDT: 78.57
  • Fraction with pLDDT ≥ 70 (very high confidence): 11%
  • Sequence Length: 2,549 amino acids

Cross-species orthologs

OrganismGene IDSymbol
Mouse (Mus musculus)ENSMUSG00000028991Mtor
Rat (Rattus norvegicus)ENSRNOG00000009615Mtor
Zebrafish (Danio rerio)ENSDARG00000053196mtor
Fruit fly (Drosophila melanogaster)FBGN0021796mTor
Worm (C. elegans)WBGENE00002583let-363
Yeast (S. cerevisiae)nonenone

Clinical variants & AI predictions

ClinVar Classification Summary

ClassificationCount
Pathogenic23
Likely Pathogenic27
Uncertain Significance~2,700+
Likely Benign~500+
Benign~500+
Conflicting Classifications~165
Total Variants~2,915

Top 30 Pathogenic/Likely Pathogenic Variants

Variant IDHGVS NotationClassification
156702c.5930C>A (p.Thr1977Lys)Pathogenic
156703c.6644C>T (p.Ser2215Phe)Pathogenic
156709c.7255G>A (p.Glu2419Lys)Pathogenic
217823c.5395G>A (p.Glu1799Lys)Pathogenic
242349c.6981G>A (p.Met2327Ile)Pathogenic
374796c.4447T>C (p.Cys1483Arg)Pathogenic
376129c.6644C>A (p.Ser2215Tyr)Pathogenic
376130c.4379T>C (p.Leu1460Pro)Pathogenic
376453c.4448G>A (p.Cys1483Tyr)Pathogenic
417723c.7280T>C (p.Leu2427Pro)Pathogenic
520633c.7238G>T (p.Ser2413Ile)Pathogenic
584432c.5930C>T (p.Thr1977Ile)Pathogenic
1296989c.5930C>G (p.Thr1977Arg)Pathogenic
1296993c.4468T>C (p.Trp1490Arg)Likely Pathogenic
1296997c.5005G>T (p.Ala1669Ser)Likely Pathogenic
1310128c.5380G>A (p.Ala1794Thr)Likely Pathogenic
1315046c.7076G>A (p.Gly2359Glu)Likely Pathogenic
1320130c.5912C>T (p.Ala1971Val)Likely Pathogenic
1339560c.6457A>G (p.Ile2153Val)Likely Pathogenic
1339561c.257del (p.Gly86fs)Pathogenic
1685378c.4298T>C (p.Leu1433Ser)Likely Pathogenic
2129739c.5664C>A (p.Phe1888Leu)Likely Pathogenic
2672094c.4376C>A (p.Ala1459Asp)Pathogenic
2672097c.5662T>C (p.Phe1888Leu)Likely Pathogenic
3399624c.4250T>C (p.Ile1417Thr)Likely Pathogenic
3731617c.5408A>C (p.His1803Pro)Likely Pathogenic
3764881c.5917A>T (p.Ile1973Phe)Likely Pathogenic
3765844c.7535A>G (p.Asp2512Gly)Likely Pathogenic
3771641c.4550C>T (p.Ala1517Val)Likely Pathogenic
4293751c.4961T>C (p.Leu1654Pro)Likely Pathogenic

Splice Effect Predictions (SpliceAI)

Total splice predictions: 8,698

Effect TypeHigh-scoring examples (score ≥ 0.93)
Acceptor Loss1:11107500 (0.99), 1:11107501 (0.99)
Acceptor Gain1:11107498 (0.98), 1:11107510 (0.99), 1:11107511 (0.99), 1:11107496 (0.94)
Donor Loss1:11108177 (1.00), 1:11108179 (1.00)
Donor Gain1:11108177 (1.00), 1:11108179 (1.00), 1:11108180 (1.00)

Top 5 highest-confidence splice predictions all score 1.0 (perfect confidence donor gain/loss events).

AlphaMissense Pathogenicity Predictions

Total predictions: ~2,000+
Likely pathogenic class: ~1,200+

Protein VariantAM PathogenicityEffect
W2549C0.999Highly pathogenic
W2549R0.999Highly pathogenic
F2548L1.000Certain pathogenic
W2545C1.000Certain pathogenic
W2545R1.000Certain pathogenic
C2539W1.000Certain pathogenic
C2539Y1.000Certain pathogenic
C2539R1.000Certain pathogenic
L2538P1.000Certain pathogenic
N2537K0.998Highly pathogenic
C2546W0.999Highly pathogenic
G2544D0.999Highly pathogenic
G2544R0.999Highly pathogenic
Q2540H0.996Highly pathogenic
Y2542D0.996Highly pathogenic
C2541R0.998Highly pathogenic
P2547R0.993Highly pathogenic
P2547H0.992Highly pathogenic
C2546R0.999Highly pathogenic
C2546F0.994Highly pathogenic
Y2542H0.988Highly pathogenic
E2536V0.994Highly pathogenic
N2537D0.993Highly pathogenic
L2538F0.994Highly pathogenic
I2543N0.973Likely pathogenic
S2534F0.974Likely pathogenic
Y2542S0.979Likely pathogenic
Q2540R0.980Likely pathogenic
Q2540P0.995Highly pathogenic
H2535R0.911Likely pathogenic

Note: Multiple rare variants show perfect (1.0) or near-perfect (0.99+) pathogenicity scores, suggesting MTOR is sensitive to specific amino acid changes in kinase domain regions. Highest-confidence predictions cluster at positions 2534–2549 (kinase domain C-terminus).

Now I’ll compile the results into the requested format.

Pathways & Gene Ontology

Biological Pathways

Reactome Pathways (15 total):

Pathway IDPathway Name
R-HSA-165159MTOR signalling
R-HSA-166208mTORC1-mediated signalling
R-HSA-1257604PIP3 activates AKT signaling
R-HSA-1632852Macroautophagy
R-HSA-3371571HSF1-dependent transactivation
R-HSA-380972Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-389357CD28 dependent PI3K/Akt signaling
R-HSA-5218920VEGFR2 mediated vascular permeability
R-HSA-5628897TP53 Regulates Metabolic Genes
R-HSA-5674400Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-6804757Regulation of TP53 Degradation
R-HSA-8943724Regulation of PTEN gene transcription
R-HSA-9639288Amino acids regulate mTORC1
R-HSA-9856530High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9920951Dengue virus modulates apoptosis

MSigDB Gene Sets: 1,017 total (Including GO-based gene sets, KEGG pathways, Reactome pathway sets, and transcription factor target sets)

Gene Ontology Annotations

Total GO Terms: 119

Biological Process (Top 20)

GO IDTerm
GO:0031929TOR signaling
GO:0038202TORC1 signaling
GO:0038203TORC2 signaling
GO:0016241regulation of macroautophagy
GO:0010507negative regulation of autophagy
GO:0016242negative regulation of macroautophagy
GO:0045948positive regulation of translational initiation
GO:0045727positive regulation of translation
GO:0031667response to nutrient levels
GO:0031669cellular response to nutrient levels
GO:0031670cellular response to nutrient
GO:0032869cellular response to insulin stimulus
GO:0043200response to amino acid
GO:0034198cellular response to amino acid starvation
GO:0071231cellular response to amino acid stimulus
GO:0071233cellular response to L-leucine
GO:0001558regulation of cell growth
GO:0030307positive regulation of cell growth
GO:0008361regulation of cell size
GO:0035264multicellular organism growth

Molecular Function (Top 20)

GO IDTerm
GO:0004672protein kinase activity
GO:0004674protein serine/threonine kinase activity
GO:0004713protein tyrosine kinase activity
GO:0004715non-membrane spanning protein tyrosine kinase activity
GO:0106310protein serine kinase activity
GO:0005524ATP binding
GO:0042802identical protein binding
GO:0051219phosphoprotein binding
GO:0044325transmembrane transporter binding
GO:0043022ribosome binding
GO:0001156TFIIIC-class transcription factor complex binding
GO:0001002RNA polymerase III type 1 promoter sequence-specific DNA binding
GO:0001003RNA polymerase III type 2 promoter sequence-specific DNA binding
GO:0001006RNA polymerase III type 3 promoter sequence-specific DNA binding
GO:0000822inositol hexakisphosphate binding
GO:0018127protein omega-hydroxylation
GO:0018128protein hydroxylation
GO:0043175RNA binding
GO:0003700DNA-binding transcription factor activity
GO:0003712transcription coregulator activity

Cellular Component (Top 20)

GO IDTerm
GO:0031931TORC1 complex
GO:0031932TORC2 complex
GO:0005634nucleus
GO:0005654nucleoplasm
GO:0005737cytoplasm
GO:0005829cytosol
GO:0005886plasma membrane
GO:0005783endoplasmic reticulum
GO:0005789endoplasmic reticulum membrane
GO:0000139Golgi membrane
GO:0005764lysosome
GO:0005765lysosomal membrane
GO:0005741mitochondrial outer membrane
GO:0005635nuclear envelope
GO:0016020membrane
GO:0012505endomembrane system
GO:0016605PML body
GO:0030425dendrite
GO:0030030cell projection organization
GO:0012505endomembrane system

Protein interactions & networks

Protein-Protein Interactions

Total Interaction Summary:

  • STRING: ~8,056 interactions
  • BioGRID: ~962 interactions
  • IntAct: ~467 interactions
  • BindingDB: ~5,782 records
  • Signaling (SIGNOR): 166 interactions

TOP 30 Highest-Confidence Interacting Proteins (STRING Database):

RankUniProt IDProtein NameSTRING InteractionsKey Role
1Q6R327Rapamycin-insensitive companion of mTOR (RICTOR)2,702mTORC2 scaffold
2Q8N122Regulatory-associated protein of mTOR (RAPTOR)3,272mTORC1 scaffold
3Q9BVC4mTOR complex subunit LST8 (MLST8)2,392Core mTOR component
4Q9BPZ7Target of rapamycin complex 2 subunit MAPKAP1 (SIN1)1,826mTORC2 component
5Q15382GTP-binding protein Rheb3,439mTORC1 activator
6Q8TB45DEP domain-containing mTOR-interacting protein (DEPDC6)1,380mTOR regulator
7P85299Proline-rich protein 5 (PRR5/PROTOR1)562mTORC2 component
8Q96B36Proline-rich AKT1 substrate 1 (PRAS40)1,762mTORC1 inhibitor
9P23443Ribosomal protein S6 kinase beta-1 (S6K1)5,172mTOR effector kinase
10O75385Serine/threonine-protein kinase ULK12,512Autophagy regulator
11P49815Tuberin (TSC2)3,586mTORC1 inhibitor
12P31749RAC-alpha serine/threonine-protein kinase (AKT1/PKB)14,324Upstream activator
13Q13541Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1/PHAS-I)1,862mTOR target, translation control
14O43156TELO2-interacting protein 1 homolog (SMG10)1,184mTOR complex assembly
15P60484Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase PTEN9,614PI3K/AKT pathway inhibitor
16Q92574Hamartin (TSC1)4,851mTORC1 inhibitor (TSC complex)
17P06730Eukaryotic translation initiation factor 4E (eIF4E)5,170Translation initiation, mTOR target
18Q6MZQ0Proline-rich protein 5-like (PRR5L/PROTOR2)576mTORC2 component
19Q9HB90Ras-related GTP-binding protein C (RagC)1,326Amino acid sensing
20Q14318Peptidyl-prolyl cis-trans isomerase FKBP83,366mTOR regulation (FK506 target)
21Q9UBS0Ribosomal protein S6 kinase beta-2 (S6K2)3,108mTOR effector kinase
22Q5VZM2Ras-related GTP-binding protein B (RagB)1,048Amino acid sensing
23P01308Insulin11,095Growth signal upstream
24Q7L523Ras-related GTP-binding protein A (RagA)977Amino acid sensing
25Q96EB6NAD-dependent protein deacetylase sirtuin-1 (SIRT1)6,954Metabolic regulator
26Q9NQX3Gephyrin2,326Scaffolding protein
27Q14457Beclin-1 (BECN1)3,790Autophagy regulator
28P08069Insulin-like growth factor 1 receptor (IGF1R)5,824Growth factor receptor
29P19484Growth hormone3,717Growth signaling
30P48736Protein kinase C alpha type (PRKCA)~1,500+Upstream signaling

Protein Similarity

Structural/Embedding Similarity (ESM2): 95 similar proteins identified. Key structural homologs include:

  • P42346 (mTOR isoform/variant)
  • Q9JLN9 (Serine/threonine-protein kinase mTOR)
  • Q14997, Q4KLU7, Q5TBA9, Q5U241 (Kinase domain homologs)
  • O94915, P21359, P51593 (Related protein kinases)

Sequence Homology (DIAMOND Similarity): 6 direct sequence homologs:

  • P42346 - mTOR (likely isoform)
  • Q9JLN9 - mTOR kinase variant
  • Q9VK45 - mTOR ortholog
  • O74630, P32600, P35169 (Fungal/invertebrate homologs)

Orthologs across species:

  • Homo sapiens: P42345 (human mTOR)
  • Mus musculus: ENSMUSG00000028991 (Mtor)
  • Drosophila melanogaster: FBGN0021796 (mTor)
  • Caenorhabditis elegans: WBGene00018496 (let-363)
  • Danio rerio: ENSDARG00000053196 (mtor)

Transcription factor regulatory data

MTOR is not a transcription factor. It is a serine/threonine-protein kinase that functions as a master regulator of cell growth and metabolism through phosphorylation of downstream targets, not gene regulation.

Upstream regulators of MTOR

TFs that regulate the MTOR gene:

Transcription FactorRegulationConfidence
SOX2ActivationHigh
ATF4–Low
CEBPB–Low
PDX1–Low
SPI1–Low

Evidence type: Predicted (CollecTRI database integrates ChIP-seq and computational predictions).

Drug & pharmacology data

MTOR is a well-established drug target with 5,174 unique molecules in ChEMBL targeting the Serine/threonine-protein kinase mTOR (CHEMBL2842).

Approved mTOR Inhibitor Drugs (Phase 4)

Top approved molecules:

MoleculeChEMBL IDDevelopment PhaseClinical TrialsKey Indications
SirolimusCHEMBL4134 (Approved)564Transplant rejection prevention, renal cell carcinoma, tuberous sclerosis-related conditions
EverolimusCHEMBL19083604 (Approved)711Breast cancer, neuroendocrine tumors, renal cell carcinoma, tuberous sclerosis angiomyolipoma
TemsirolimusCHEMBL12011824 (Approved)197Renal cell carcinoma, mantle cell lymphoma, neuroendocrine tumors

Additional Phase 3-4 inhibitors in development include compounds in trials for various malignancies and transplantation indications.

Representative Clinical Trials (TOP 20)

Recent/Active trials with mTOR inhibitors:

  1. NCT06584773 — Efficacy of quadruple immunosuppressor regimen with mTOR inhibitors in sensitized kidney transplant patients | Phase 4 | RECRUITING
  2. NCT06942156 — Optimize immunosuppressive therapy using everolimus and low-dose calcineurin inhibitors in heart transplant patients in Korea | Phase 4 | NOT_YET_RECRUITING
  3. NCT04433572 — Temsirolimus adventitial delivery to improve angioplasty revascularization outcomes below the knee | Phase 3 | RECRUITING
  4. NCT04921722 — Percutaneous administration of sirolimus for superficial complicated vascular anomalies | Phase 4 | RECRUITING
  5. NCT04700709 — Efficacy and safety of sirolimus plus CNI vs MMF plus CNI in ABO-incompatible kidney transplant recipients | Phase 4 | UNKNOWN
  6. NCT06722586 — Sirolimus monotherapy for antiphospholipid antibody related thrombocytopenia | Phase 4 | RECRUITING
  7. NCT05252585 — Safety and efficacy of everolimus in Taiwanese patients with tuberous sclerosis complex-associated angiomyolipoma | Phase 4 | ACTIVE_NOT_RECRUITING
  8. NCT04471441 — Efficacy and safety of everolimus versus mycophenolate mofetil in liver transplant recipients | Phase 4 | UNKNOWN
  9. NCT04867720 — Safety and efficacy of everolimus tablet plus tacrolimus in primary living donor liver transplant recipients | Phase 4 | UNKNOWN
  10. NCT03525834 — Safety and efficacy of everolimus in Chinese adult patients with angiomyolipoma associated with tuberous sclerosis | Phase 4 | COMPLETED
  11. NCT02567435 — Combination chemotherapy with or without temsirolimus in treating intermediate risk rhabdomyosarcoma | Phase 3 | ACTIVE_NOT_RECRUITING
  12. NCT02429869 — Impact of everolimus on HIV persistence post kidney or liver transplant | Phase 4 | COMPLETED
  13. NCT03415750 — Everolimus and tacrolimus combination for regression of left ventricular hypertrophy in renal transplants | Phase 4 | COMPLETED
  14. NCT03468478 — Comparison of efficacy and safety of sirolimus versus everolimus versus mycophenolate in kidney transplantation | Phase 4 | COMPLETED
  15. NCT01646021 — Ibrutinib versus temsirolimus in patients with relapsed/refractory mantle cell lymphoma | Phase 3 | COMPLETED
  16. NCT00631371 — Bevacizumab + temsirolimus vs bevacizumab + interferon-alfa in advanced renal cell carcinoma | Phase 3 | COMPLETED
  17. NCT00510068 — Everolimus (RAD001) vs placebo in patients with advanced neuroendocrine tumors | Phase 3 | COMPLETED
  18. NCT00474786 — Temsirolimus versus sorafenib as second-line therapy in advanced RCC after sunitinib failure | Phase 3 | COMPLETED
  19. NCT01180049 — Comparison of 2 doses of temsirolimus in patients with mantle cell lymphoma | Phase 4 | COMPLETED
  20. NCT00117598 — Study evaluating temsirolimus (CCI-779) in mantle cell lymphoma | Phase 3 | COMPLETED

Pharmacogenomics & Dosing

Known drug-gene interactions:

  • CYP3A4 metabolism: All mTOR inhibitors are CYP3A4 substrates. Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may increase mTOR inhibitor levels; inducers (e.g., rifampicin) may decrease levels. Dosing adjustments required.
  • Drug-drug interactions: Significant interactions with calcineurin inhibitors (tacrolimus, cyclosporine) commonly used in transplant patients—therapeutic drug monitoring recommended.
  • Sirolimus: Therapeutic drug monitoring at 5-15 ng/mL typical; steady-state reached in 2 weeks; fat-soluble with large distribution volume.
  • Everolimus: Typical dosing 0.75-1.5 mg BID; therapeutic drug monitoring at 3-8 ng/mL recommended.
  • Temsirolimus: IV infusion 25 mg weekly; no routine therapeutic drug monitoring standard.

Pharmacogenomic biomarkers currently established: Limited pharmacogenomic biomarkers for patient selection; efficacy/toxicity varies with individual CYP3A4 phenotype, but routine genotyping not standard practice. Response assessment primarily clinical (imaging for tumors, graft function for transplant).

Expression profiles

Tissue expression (Bgee)

MTOR shows ubiquitous expression across tissues with an average score of 81.67 (max 93.51).

RankTissueExpression scoreQuality
1Primordial germ cell in gonad93.51Gold
2Right hemisphere of cerebellum92.71Gold
3Cerebellar hemisphere92.28Gold
4Cerebellar cortex92.12Gold
5Left testis92.08Gold
6Right testis91.90Gold
7Gastrocnemius91.56Gold
8Right frontal lobe91.20Gold
9Muscle of leg91.14Gold
10Hindlimb stylopod muscle90.74Gold
11Male germ line stem cell in testis90.73Gold
12Ventricular zone90.60Gold
13Apex of heart90.27Gold
14Muscle layer of sigmoid colon90.11Gold
15Testis90.10Gold
16Lower esophagus muscularis layer90.04Gold
17Lower esophagus90.02Gold
18Esophagogastric junction muscularis propria89.74Gold
19Tibial nerve89.65Gold
20Adenohypophysis89.59Gold
21Cerebellum89.47Gold
22Metanephros cortex89.43Gold
23Stromal cell of endometrium89.38Gold
24Right lobe of liver89.08Gold
25Cortical plate89.07Gold
26Right adrenal gland cortex88.85Gold
27Right adrenal gland88.58Gold
28Popliteal artery88.48Gold
29Tibial artery88.47Gold
30Right atrium auricular region88.46Gold

Key patterns: MTOR shows particularly high expression in germ cells and testis (consistent with germline function), cerebellum and brain regions (neuronal function), and skeletal muscles. The ubiquitous pattern reflects its fundamental role in mTORC1/mTORC2 signaling across cell types.

Single-cell expression

MTOR is covered in the Single Cell Expression Atlas (1 experiment). The gene shows widespread presence across cell populations reflecting its core metabolic and growth-regulatory functions in diverse cell types.

Disease associations

Mendelian / monogenic disease

DiseaseDisease IDInheritanceEvidence Level
Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndromeOMIM:616638, Orphanet:457485, MONDO:0014716Autosomal dominantDefinitive / Strong / Supportive
Isolated focal cortical dysplasia type IIMONDO:0011818, Orphanet:268994––
Familial thoracic aortic aneurysm and aortic dissectionMONDO:0019625, Orphanet:91387––
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genesMONDO:0100283––
Dystonia, early-onset, and/or spastic paraplegiaMONDO:0859215––
CEBALID syndromeMONDO:0032908––
Facial dysmorphism-Intellectual disability-rhombencephalosynapsis syndromeOrphanet:693549––
HemimegalencephalyMONDO:0020492, Orphanet:99802––
Hereditary papillary renal cell carcinomaOrphanet:47044––

Phenotype associations (top 30 HPO terms)

HPO IDPhenotype
HP:0000256Macrocephaly
HP:0001249Intellectual disability
HP:0001250Seizure
HP:0001263Global developmental delay
HP:0000006Autosomal dominant inheritance
HP:0005257Thoracic hypoplasia
HP:0001355Megalencephaly
HP:0001252Hypotonia
HP:0002539Cortical dysplasia
HP:0001290Generalized hypotonia
HP:0002119Ventriculomegaly
HP:0002126Polymicrogyria
HP:0010864Severe intellectual disability
HP:0001288Gait disturbance
HP:0001328Specific learning disability
HP:0002197Generalized-onset seizure
HP:0011097Epileptic spasm
HP:0007359Focal-onset seizure
HP:0001273Abnormal corpus callosum morphology
HP:0002079Hypoplasia of the corpus callosum
HP:0001999Abnormal facial shape
HP:0002007Frontal bossing
HP:0000348High forehead
HP:0011220Prominent forehead
HP:0000316Hypertelorism
HP:0001520Large for gestational age
HP:0001943Hypoglycemia
HP:0001998Neonatal hypoglycemia
HP:0001537Umbilical hernia
HP:0001538Protuberant abdomen

Complex-disease / GWAS associations (top 12)

TraitGWAS Variant/Study IDP-valueGene
Corneal curvatureGCST002502_36.0e-18MTOR
Mean spheric corpuscular volumeGCST90002397_701.0e-21MTOR
Mean reticulocyte volumeGCST90002396_875.0e-16MTOR
Mean corpuscular volumeGCST90002392_3374.0e-09MTOR
Corneal curvatureGCST001101_14.0e-13MTOR
Body mass index and type 2 diabetes (pairwise)GCST011329_142.0e-08MTOR
A body shape indexGCST90020024_10475.0e-09MTOR
Heel bone mineral densityGCST006288_281.0e-10MTOR
Heel bone mineral densityGCST006288_2102.0e-06MTOR
Body mass indexGCST002783_2422.0e-06MTOR
Body mass indexGCST002783_6159.0e-06MTOR
Beard thicknessGCST003475_74.0e-07CIROZ

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 42 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, cdd, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, ensembl, entrez, esm2_similarity, exon, gencc, go, gwas, hgnc, hpa, hpo, intact, interpro, mim, mondo, msigdb, orphanet, ortholog, orthologentrez, pdb, pfam, reactome, refseq, scxa_expression, signor, smart, spliceai, string_interaction, transcript, uniprot
Generated: 2026-05-25 — For the latest data, query BioBTree directly via MCP or API.
View API calls (178)