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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RPTOR
regulatory associated protein of MTOR complex 1
Chromosome 17 · 17q25.3
NCBI Gene: 57521Ensembl: ENSG00000141564.16HGNC: HGNC:30287UniProt: Q8N122
296PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Trending
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein serine/threonine kinase activityprotein bindingprotein kinase bindingprotein serine/threonine kinase inhibitor activityAbnormality of the skeletal systemneurodegenerative diseasecongestive heart failureobesity
✦AI Summary

RPTOR (regulatory associated protein of mTOR complex 1) is an essential regulatory component of mTORC1, serving as both a molecular adapter and substrate-specific scaffold. RPTOR mediates mTORC1 recruitment to lysosomal membranes through interactions with Rag GTPases in response to amino acid availability 1. As a substrate adapter, RPTOR promotes substrate specificity by binding TOS motif-containing proteins and directing them to the mTOR kinase domain for phosphorylation. The mTORC1 complex containing RPTOR phosphorylates key substrates including RPS6KB1, EIF4EBP1, ULK1, ATG13, and TFEB to regulate protein synthesis, autophagy, and lysosomal biogenesis 2. RPTOR is subject to regulatory phosphorylation by AMPK, which inhibits mTORC1 activity and promotes autophagy through TFEB activation 34. In disease contexts, RPTOR-containing mTORC1 is dysregulated in nonalcoholic fatty liver disease, where inflammatory signals like STING1 can aberrantly activate the complex, restricting beneficial lipophagy and promoting hepatic steatosis 5. The complex also plays roles in cellular senescence through mTORC2 regulation 6. RPTOR's function as a critical node in nutrient sensing and metabolic regulation makes it important for understanding growth control and metabolic diseases.

Sources cited
1
RPTOR mediates amino acid-sensitive interaction with mTORC1 and promotes mTORC1 localization to cellular compartments
PMID: 18497260
2
RPTOR structure in the megacomplex showing how it presents substrates like TFEB to mTOR kinase domain through Rag-Ragulator interactions
PMID: 36697823
3
RPTOR phosphorylation by AMPK leads to mTORC1 inactivation and TFEB nuclear translocation promoting autophagy
PMID: 33190588
4
AMPK-mediated RPTOR phosphorylation inhibits mTORC1 and activates TFEB-mediated autophagy pathway in NASH treatment
PMID: 39936600
5
STING1 interacts with RPTOR and other mTORC1 components to promote complex formation and restrict lipophagy in lipotoxic conditions
PMID: 34382907
6
mTORC1 containing RPTOR is involved in autophagy-driven cellular senescence and myofibroblast differentiation
PMID: 31931659
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.44Moderate
neurodegenerative diseaseOpen Targets
0.44Moderate
congestive heart failureOpen Targets
0.38Weak
obesityOpen Targets
0.37Weak
dengue diseaseOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.36Weak
abscessOpen Targets
0.30Weak
cellulitisOpen Targets
0.30Weak
schizophreniaOpen Targets
0.30Weak
hypertensionOpen Targets
0.29Weak
metabolic syndromeOpen Targets
0.28Weak
biliary tract diseaseOpen Targets
0.26Weak
goutOpen Targets
0.25Weak
intestinal impactionOpen Targets
0.25Weak
overnutritionOpen Targets
0.24Weak
cervical carcinomaOpen Targets
0.24Weak
Abruptio PlacentaeOpen Targets
0.23Weak
sialolithiasisOpen Targets
0.22Weak
corneal neovascularizationOpen Targets
0.22Weak
Moyamoya diseaseOpen Targets
0.22Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
INDOXIMODPhase II/III
mTORC1 activator
melanoma
Related Genes
EIF4BProtein interaction100%EIF4EProtein interaction100%EIF4EBP2Protein interaction100%IGBP1Protein interaction100%TFEBProtein interaction100%FKBP8Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
87%
Lung
75%
Liver
68%
Ovary
67%
Bone Marrow
47%
Gene Interaction Network
Click a node to explore
RPTOREIF4BEIF4EEIF4EBP2IGBP1TFEBFKBP8
PROTEIN STRUCTURE
Preparing viewer…
PDB8ERA · 2.86 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.20Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.10–0.20]
RankingsWhere RPTOR stands among ~20K protein-coding genes
  • #1,192of 20,598
    Most Researched296 · top 10%
  • #480of 17,882
    Most Constrained (LOEUF)0.20 · top 5%
Genes detectedRPTOR
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation.
PMID: 33190588
Autophagy · 2021
1.00
2
Buddleoside alleviates nonalcoholic steatohepatitis by targeting the AMPK-TFEB signaling pathway.
PMID: 39936600
Autophagy · 2025
0.90
3
Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease.
PMID: 37700498
Autophagy · 2024
0.80
4
Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex.
PMID: 36697823
Nature · 2023
0.70
5
AMPK phosphorylation of raptor mediates a metabolic checkpoint.
PMID: 18439900
Mol Cell · 2008
0.64