RHEB (Ras Homolog Enriched in Brain)
Key Regulator of mTORC1 Signaling and Cell Growth
Gene Information Card
| Symbol | RHEB |
|---|---|
| Full Name | Ras Homolog Enriched in Brain |
| Gene Type | Protein coding |
| Chromosomal Location | 7q36.1 |
| NCBI Gene ID | 6009 ncbi.nlm.nih.gov/gene/6009 |
| Ensembl ID | ENSG00000106615 |
| UniProt ID | Q15382 |
| OMIM ID | 601293 |
| HGNC ID | 10011 |
| Aliases | RHEB2, Rheb |
Description
RHEB (Ras Homolog Enriched in Brain) is a small GTPase that belongs to the Ras superfamily. It acts as a critical activator of the mechanistic target of rapamycin complex 1 (mTORC1), a central regulator of cell growth, proliferation, and metabolism. RHEB is activated when bound to GTP and inhibited by the TSC1-TSC2 complex, which promotes its GTPase activity. Dysregulation of RHEB is implicated in tuberous sclerosis complex, cancer, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tuberous Sclerosis Complex (TSC) | Loss of TSC1/TSC2 leads to RHEB hyperactivation and mTORC1 overactivity, causing benign tumors. | PMID: 12651872 |
| Prostate Cancer | RHEB overexpression and activation promote mTORC1 signaling and tumor growth. | PMID: 20010870 |
| Lung Cancer | RHEB mutations and amplification contribute to mTORC1-driven proliferation. | PMID: 21502514 |
| Cardiac Hypertrophy | RHEB-mediated mTORC1 activation induces pathological cardiac growth. | PMID: 20526336 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.3 | Medium |
| Liver | 6.1 | Medium |
| Kidney | 7.2 | Medium |
| Lung | 5.8 | Medium |
| Skeletal Muscle | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| HeLa | 10.8 | Moderate expression in cervical cancer cells |
| A549 | 9.5 | Moderate expression in lung cancer cells |
| MCF7 | 7.3 | Low expression in breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.37C>T (p.Arg13Cys) | Missense | Rare | Alters GTP binding and reduces mTORC1 activation |
| c.101A>G (p.Tyr34Cys) | Missense | Rare | Gain-of-function, increases mTORC1 signaling |
| c.148G>A (p.Gly50Ser) | Missense | Rare | Loss-of-function, impairs nucleotide binding |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair GTP binding or GTPase activity reduce RHEB's ability to activate mTORC1, leading to decreased cell growth.
Gain of Function (GOF)
Mutations that enhance GTP loading or reduce GTP hydrolysis increase mTORC1 signaling, promoting uncontrolled cell proliferation.
Dominant Negative (DN)
Dominant-negative RHEB mutants (e.g., defective in nucleotide binding) can sequester downstream effectors and inhibit mTORC1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mTOR signaling pathway (KEGG: hsa04150)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Insulin signaling pathway (KEGG: hsa04910)
• Regulation of eIF4E and p70 S6 Kinase (Reactome: R-HSA-166208)
Protein Summary
RHEB is a 184-amino acid small GTPase with a molecular weight of approximately 20.5 kDa. It localizes to the lysosomal membrane where it directly activates mTORC1 in response to growth factors and amino acids. The protein contains a conserved G domain for nucleotide binding and a C-terminal CAAX motif for prenylation and membrane anchoring. RHEB activity is tightly regulated by the TSC1-TSC2 complex, which acts as a GTPase-activating protein (GAP).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RHEBL1 Knockout HEK293 Cell Line | EDJ-KQ7917 | Human | 121268 | Details Get a Quote |
| RHEBL1 Knockout A-549 Cell Line | EDJ-KQ33544 | Human | 121268 | Details Get a Quote |
| RHEBL1 Knockout HCT 116 Cell Line | EDJ-KQ33545 | Human | 121268 | Details Get a Quote |
| RHEBL1 Knockout HeLa Cell Line | EDJ-KQ33546 | Human | 121268 | Details Get a Quote |
| Rheb Knockout RAW 264.7 Cell Line | EDJ-KZ428 | Mouse | 19744 | Details Get a Quote |
