RRAGA: Ras-Related GTP Binding A
A key regulator of mTORC1 signaling and cellular growth
Gene Information Card
| Symbol | RRAGA |
|---|---|
| Full Name | Ras Related GTP Binding A |
| Gene Type | Protein coding |
| Chromosomal Location | 9p22.1 |
| NCBI Gene ID | 10670 ncbi.nlm.nih.gov/gene/10670 |
| Ensembl ID | ENSG00000136869 |
| UniProt ID | Q7L523 |
| OMIM ID | 612194 |
| HGNC ID | 16963 |
| Aliases | RagA, GTR2, FIP-3 |
Description
RRAGA encodes a member of the Ras-related small GTPase family. The protein forms a heterodimer with RRAGC and functions as a key activator of the mechanistic target of rapamycin complex 1 (mTORC1) in response to amino acid availability. It cycles between an active GTP-bound state and an inactive GDP-bound state, regulating cellular growth, metabolism, and autophagy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | Dysregulated mTORC1 signaling due to RRAGA mutations or overexpression promotes uncontrolled cell proliferation | PMID: 23563266, COSMIC |
| Epileptic encephalopathy | De novo missense variants in RRAGA impair GTP hydrolysis, leading to mTORC1 hyperactivation and neurodevelopmental defects | PMID: 31006510, ClinVar |
| Tuberous sclerosis complex (modifier) | Altered RRAGA activity may modulate mTORC1 signaling in TSC patients | PMID: 21575865 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 10.1 | Medium |
| Kidney | 9.7 | Medium |
| Testis | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.0 | High expression |
| HeLa | 11.5 | Medium expression |
| A549 | 9.8 | Medium expression |
| K562 | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.485G>A (p.Arg162Gln) | Missense | <0.01% | Impaired GTP hydrolysis, constitutive mTORC1 activation |
| c.544C>T (p.Arg182Trp) | Missense | <0.01% | Gain-of-function, associated with epileptic encephalopathy |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss-of-function, reduced protein expression |
Mutation functional classification
Loss of Function (LOF)
Rare start-loss or nonsense variants that reduce RRAGA protein levels or disrupt GTP binding.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg162Gln, p.Arg182Trp) that impair GTP hydrolysis, locking RRAGA in an active state and hyperactivating mTORC1.
Dominant Negative (DN)
Not well characterized; some variants may interfere with heterodimer formation with RRAGC.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • protein heterodimerization activity | • regulation of TOR signaling |
| • cellular response to amino acid stimulus | • autophagy |
Pathways
• mTOR signaling pathway (KEGG: hsa04150)
• Regulation of mTORC1 by amino acids (Reactome: R-HSA-9639288)
• Autophagy (KEGG: hsa04140)
Protein Summary
RRAGA is a 313-amino acid small GTPase that localizes to the lysosomal surface. In its GTP-bound form, it recruits mTORC1 to the lysosome, enabling its activation by Rheb. The protein contains an N-terminal GTPase domain and a C-terminal domain that mediates interaction with RRAGC. Post-translational modifications include farnesylation at the C-terminus, which is essential for membrane association.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RRAGA Knockout HEK293 Cell Line | EDJ-KQ1154 | Human | 10670 | Details Get a Quote |
| RRAGA Knockout A-549 Cell Line | EDJ-KQ20384 | Human | 10670 | Details Get a Quote |
| RRAGA Knockout HCT 116 Cell Line | EDJ-KQ20385 | Human | 10670 | Details Get a Quote |
| RRAGA Knockout HeLa Cell Line | EDJ-KQ20386 | Human | 10670 | Details Get a Quote |
