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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RRAGA
Ras related GTP binding A
Chromosome 9 · 9p22.1
NCBI Gene: 10670Ensembl: ENSG00000155876.6HGNC: HGNC:16963UniProt: Q7L523
100PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GATOR1 complexGTPase activityprotein bindingGTP bindingcataractneurodegenerative diseaseprostate carcinomathyroid cancer
✦AI Summary

RRAGA (Ras-related GTP-binding protein A) is a key regulator of mTORC1 nutrient sensing on the lysosomal membrane. RRAGA functions as a GTPase that senses amino acid availability, particularly leucine, and controls mTORC1 recruitment to lysosomes for activation 1. As a component of the Rag-Ragulator complex, RRAGA serves as the central organizer of mTORC1 pathway architecture, with its nucleotide state controlling lysosomal association of regulatory complexes including GATOR1, GATOR2, and KICSTOR 2. The Rag-Ragulator complex presents substrates like TFEB to mTORC1 for phosphorylation in a RagC GDP-dependent manner 3. RRAGA participates in stress responses, where membrane Atg8ylation recruits RRAGA-containing complexes to damaged lysosomes to inactivate mTORC1 4. RRAGA mutations cause autosomal dominant cataracts through disrupted mTORC1 signaling, increased lysosomal RRAGA relocation, elevated mTORC1 phosphorylation, and compromised autophagy in lens epithelial cells 5. RRAGA-dependent mTORC1 inhibition promotes autophagy and virus replication during glucosamine treatment 6, while STING1-mediated MTORC1 activation involves RRAGA and RRAGC in hepatic lipid metabolism regulation 7. RRAGA overexpression has been associated with depression onset 1.

Sources cited
1
RRAGA senses amino acid availability and controls mTORC1 translocation to lysosomal membrane; overexpression associated with depression
PMID: 35870248
2
Rag-Ragulator complex with RRAGA is central organizer of mTORC1 nutrient-sensing pathway; RagA nucleotide state controls GATOR recruitment
PMID: 39163330
3
RagC GDP-dependent contacts present TFEB to mTORC1 for phosphorylation in megacomplex structure
PMID: 36697823
4
RRAGA-containing Ragulator complex contributes to mTOR inactivation at damaged lysosomes via Atg8ylation
PMID: 36394332
5
RRAGA mutations cause autosomal dominant cataracts through disrupted mTORC1 signaling and altered autophagy
PMID: 27294265
6
RRAGA mediates glucosamine-induced mTORC1 inhibition and autophagy to promote viral replication
PMID: 31204557
7
RRAGA and RRAGC involved in STING1-mediated mTORC1 activation regulating hepatic lipid metabolism
PMID: 34382907
Disease Associationsⓘ20
cataractOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.33Weak
prostate carcinomaOpen Targets
0.19Weak
thyroid cancerOpen Targets
0.17Weak
high grade ovarian serous adenocarcinomaOpen Targets
0.13Weak
Abnormality of the skeletal systemOpen Targets
0.12Weak
type 2 diabetes mellitusOpen Targets
0.12Weak
scoliosisOpen Targets
0.11Weak
basal cell carcinomaOpen Targets
0.10Suggestive
response to antihypertensive drugOpen Targets
0.09Suggestive
poisoningOpen Targets
0.08Suggestive
response to xenobiotic stimulusOpen Targets
0.08Suggestive
Abruptio PlacentaeOpen Targets
0.08Suggestive
malignant renal pelvis neoplasmOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
cartilage diseaseOpen Targets
0.08Suggestive
type 1 diabetes mellitusOpen Targets
0.07Suggestive
gestational diabetesOpen Targets
0.07Suggestive
kidney diseaseOpen Targets
0.07Suggestive
chronic kidney diseaseOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SKP2Protein interaction100%TFEBProtein interaction100%TMEM11Protein interaction100%TBC1D7Protein interaction100%NOL8Protein interaction97%FNIP2Protein interaction95%
Tissue Expression6 tissues
Brain
100%
Heart
76%
Ovary
54%
Liver
48%
Lung
47%
Bone Marrow
21%
Gene Interaction Network
Click a node to explore
RRAGASKP2TFEBTMEM11TBC1D7NOL8FNIP2
PROTEIN STRUCTURE
Preparing viewer…
PDB5X6V · 2.02 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.84LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF0.51 [0.32–0.84]
RankingsWhere RRAGA stands among ~20K protein-coding genes
  • #4,807of 20,598
    Most Researched100 · top quartile
  • #7,186of 17,882
    Most Constrained (LOEUF)0.84
Genes detectedRRAGA
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy.
PMID: 34382907
Autophagy · 2022
1.00
2
Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex.
PMID: 36697823
Nature · 2023
0.90
3
Membrane Atg8ylation, stress granule formation, and MTOR regulation during lysosomal damage.
PMID: 36394332
Autophagy · 2023
0.80
4
Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway.
PMID: 39163330
Proc Natl Acad Sci U S A · 2024
0.70
5
Glucosamine promotes hepatitis B virus replication through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling.
PMID: 31204557
Autophagy · 2020
0.60