RRAGC (Ras Related GTP Binding C)
A key regulator of mTORC1 signaling and amino acid sensing
Gene Information Card
| Symbol | RRAGC |
|---|---|
| Full Name | Ras related GTP binding C |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 64121 ncbi.nlm.nih.gov/gene/64121 |
| Ensembl ID | ENSG00000116918 |
| UniProt ID | Q9HB90 |
| OMIM ID | 608267 |
| HGNC ID | 17302 |
| Aliases | GTR2, RAGC, dJ646B12.1 |
Description
RRAGC encodes a member of the Ras-related small GTPase family that functions as a critical regulator of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. In response to amino acid availability, RRAGC interacts with the GATOR1 and GATOR2 complexes to modulate mTORC1 activity, thereby controlling cell growth, proliferation, and metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 66 | Loss-of-function mutations in RRAGC impair mTORC1 activation in immune cells, leading to defective T-cell proliferation and antibody responses. | PMID: 31104773 |
| Lung adenocarcinoma | Gain-of-function mutations in RRAGC (e.g., p.Ser75Leu) constitutively activate mTORC1, promoting tumor growth. | PMID: 31031016 |
| Colorectal cancer | RRAGC overexpression and activating mutations contribute to mTORC1 hyperactivation and resistance to therapy. | PMID: 29301961 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.3 | Medium |
| Kidney | 9.8 | Medium |
| Liver | 7.5 | Low |
| Brain | 5.2 | Low |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 15.6 | High expression |
| HEK293 (embryonic kidney) | 11.2 | Moderate expression |
| HeLa (cervical cancer) | 8.9 | Moderate expression |
| K562 (leukemia) | 3.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Ser75Leu | Missense | 0.5% in lung adenocarcinoma | Gain-of-function; constitutive mTORC1 activation |
| p.Leu82Pro | Missense | Rare | Loss-of-function; impaired GTP binding |
| p.Arg90Gln | Missense | 0.2% in colorectal cancer | Gain-of-function; increased mTORC1 signaling |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Leu82Pro impair GTP binding and reduce mTORC1 activation, leading to immunodeficiency.
Gain of Function (GOF)
Mutations such as p.Ser75Leu enhance GTP loading and constitutive mTORC1 activation, promoting oncogenesis.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported in RRAGC.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • mTORC1 signaling | • cellular response to amino acid stimulus |
| • regulation of cell growth |
Pathways
• mTOR signaling pathway (KEGG: hsa04150)
• Amino acid sensing via GATOR complex
• Regulation of TORC1 signaling (Reactome: R-HSA-165159)
Protein Summary
RRAGC is a 399-amino acid protein that belongs to the Ras-related GTPase family. It contains a conserved GTP-binding domain and localizes to the lysosomal surface, where it interacts with the Ragulator complex and GATOR1/2 to regulate mTORC1 activity in response to amino acid levels. The protein cycles between an active GTP-bound state and an inactive GDP-bound state, with mutations disrupting this cycle linked to cancer and immune disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RRAGC Knockout HEK293 Cell Line | EDJ-KQ1155 | Human | 64121 | Details Get a Quote |
| RRAGC Knockout A-549 Cell Line | EDJ-KQ20391 | Human | 64121 | Details Get a Quote |
| RRAGC Knockout HCT 116 Cell Line | EDJ-KQ20392 | Human | 64121 | Details Get a Quote |
| RRAGC Knockout HeLa Cell Line | EDJ-KQ20393 | Human | 64121 | Details Get a Quote |
