RPTOR

Chr 17

regulatory associated protein of MTOR complex 1

Also known as: KOG1, Mip1

NCBI Gene: 57521UniProt: Q8N122

This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

146
ClinVar variants
17
Pathogenic / LP
1.00
pLI score· HI
4.9
Missense Z· constrained
0.10
LOEUF· LoF intolerant
0
Active trials
Clinical Summary— RPTOR
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 113 VUS of 146 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/RPTOR?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.10LOEUF
pLI 1.000
Z-score 7.81
OE 0.04 (0.02–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.94Z-score
OE missense 0.53 (0.49–0.57)
473 obs / 886.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.02–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.49–0.57)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 3 / 76.8Missense obs/exp: 473 / 886.9Syn Z: -0.17

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS113
Likely Benign9
Benign7
16
Pathogenic
1
Likely Pathogenic
113
VUS
9
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
103
10
0
113
Likely Benign
0
5
1
3
9
Benign
0
0
1
6
7
Total0108299146

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RPTOR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy.
Liu K et al.·Autophagy
2022
RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding.
Lin Y et al.·J Exp Clin Cancer Res
2024
Common variants of ZNF750, RPTOR and TRAF3IP2 genes and psoriasis risk.
Dębniak T et al.·Arch Dermatol Res
2014
Sex-dependent molecular landscape of Alzheimer's disease revealed by large-scale single-cell transcriptomics.
Soudy M et al.·Alzheimers Dement
2025
RPTOR, a novel target of miR-155, elicits a fibrotic phenotype of cystic fibrosis lung epithelium by upregulating CTGF.
Tsuchiya M et al.·RNA Biol
2016
Prognostic Implications of an Autophagy-related Gene Signature in Pancreatic Ductal Adenocarcinoma.
Liu WS et al.·Am J Clin Oncol
2022
Treatment patterns, clinical outcomes and gene mutation characteristics of hepatitis B virus-associated mantle cell lymphoma.
Feng J et al.·Hematol Oncol
2024
mTOR Inhibition Promotes Pneumonitis through Inducing Endothelial Contraction and Hyperpermeability.
Chen X et al.·Am J Respir Cell Mol Biol
2021
Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy.
Martino D et al.·Nat Commun
2018
mTOR acts as a pivotal signaling hub for neural crest cells during craniofacial development.
Nie X et al.·PLoS Genet
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients