RRAGD: Ras-Related GTP Binding D
A key regulator of mTORC1 signaling and amino acid sensing
Gene Information Card
| Symbol | RRAGD |
|---|---|
| Full Name | Ras Related GTP Binding D |
| Gene Type | Protein coding |
| Chromosomal Location | 6q25.3 |
| NCBI Gene ID | 58528 ncbi.nlm.nih.gov/gene/58528 |
| Ensembl ID | ENSG00000125046 |
| UniProt ID | Q9NQL2 |
| OMIM ID | 612194 |
| HGNC ID | 19903 |
| Aliases | Rag D, bA465E1.1 |
Description
RRAGD encodes a member of the GTR/Rag GTPase family. The protein forms heterodimers with RRAGA/B/C and is essential for amino acid-stimulated activation of mTORC1, a master regulator of cell growth and metabolism. RRAGD localizes to the lysosomal membrane and recruits mTORC1 in response to amino acid availability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Renal hypomagnesemia 7 with or without dilated cardiomyopathy | Dominant-negative RRAGD mutations impair mTORC1 signaling, leading to altered ion transport and mitochondrial dysfunction | PMID: 31110393, ClinVar |
| Nephropathy with hypomagnesemia | Loss-of-function variants disrupt renal magnesium handling | OMIM #619406 |
| Cancer (various) | RRAGD overexpression or gain-of-function may hyperactivate mTORC1, promoting cell proliferation | COSMIC, PMID: 25686104 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Heart | 7.1 | Medium |
| Brain | 5.4 | Low |
| Skeletal muscle | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HepG2 | 9.8 | Moderate expression |
| A549 | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.59G>A (p.Arg20His) | Missense | <0.01% | Dominant-negative; associated with renal hypomagnesemia |
| c.76C>T (p.Arg26Cys) | Missense | <0.01% | Impaired GTP binding; loss of function |
| c.437A>G (p.Asn146Ser) | Missense | <0.01% | Reduced mTORC1 activation |
Mutation functional classification
Loss of Function (LOF)
Mutations impairing GTP binding or heterodimerization reduce mTORC1 activation.
Gain of Function (GOF)
Not well documented; overexpression may enhance mTORC1 signaling.
Dominant Negative (DN)
p.Arg20His and p.Arg26Cys act as dominant-negative by disrupting Rag heterodimer function.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding | • GTPase activity |
| • lysosomal membrane | • TORC1 signaling |
| • cellular response to amino acid stimulus |
Pathways
• mTORC1 signaling
• Amino acid sensing
• Regulation of cell growth
Protein Summary
RRAGD is a 401-amino acid GTPase that cycles between GDP-bound (inactive) and GTP-bound (active) states. It forms a heterodimeric complex with RRAGA/B/C and localizes to the lysosomal surface. Upon amino acid stimulation, RRAGD recruits mTORC1 to the lysosome for activation by RHEB. Mutations in RRAGD cause renal hypomagnesemia and dilated cardiomyopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RRAGD Knockout HEK293 Cell Line | EDJ-KQ1156 | Human | 58528 | Details Get a Quote |
| RRAGD Knockout A-549 Cell Line | EDJ-KQ20394 | Human | 58528 | Details Get a Quote |
| RRAGD Knockout HCT 116 Cell Line | EDJ-KQ20395 | Human | 58528 | Details Get a Quote |
| RRAGD Knockout HeLa Cell Line | EDJ-KQ56950 | Human | 58528 | Details Get a Quote |
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