{"entity":{"id":"rheb","kind":"target","name":"RHEB","aka":["Ras homolog, mTORC1 binding","GTP-binding protein Rheb","RHEB2"],"tldr":"RHEB (GTP-binding protein Rheb) is an enzyme. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma.","summary":"Small GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. In response to nutrients, growth factors or amino acids, specifically activates the protein kinase activity of MTOR, the catalytic component of the mTORC1 complex: acts by causing a conformational change that allows the alignment of residues in the active site of MTOR, thereby enhancing the phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). RHEB is also required for localisation of the TSC-TBC complex to lysosomal membranes.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Sirolimus.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:10011","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10011"},{"label":"UniProt Q15382","url":"https://www.uniprot.org/uniprotkb/Q15382/entry"},{"label":"NCBI Gene 6009","url":"https://www.ncbi.nlm.nih.gov/gene/6009"},{"label":"Ensembl ENSG00000106615","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000106615"}],"tags":["cancer-genes-wave"],"related":["civic"],"cancers":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 1 therapies; CIViC holds 1 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"RHEB","role":["drug-target","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:10011","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10011","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q15382","url":"https://www.uniprot.org/uniprotkb/Q15382/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene RHEB","url":"https://civicdb.org/features/4868","note":"1 evidence items, 0 assertions, 1 variants; diseases: Kidney Cancer (GraphQL API, CC0)"}],"specificity":"broadly-expressed","distribution":"one-type","specificityNote":"Broadly expressed or essential: HPA lists RHEB among essential proteins and finds the RNA at low tissue specificity; a medicine acting on the wild-type protein would expose normal tissue too. HPA RHEB: RNA low tissue specificity; no normal tissue stained high; highest cancer staining colorectal cancer (6 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Renal cell carcinoma); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas RHEB tissue","url":"https://www.proteinatlas.org/ENSG00000106615-RHEB/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000106615 associations","url":"https://platform.opentargets.org/target/ENSG00000106615/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:10011","ensembl":"ENSG00000106615","uniprot":"Q15382","entrez":"6009","firstDescribed":1995,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Gromov P.S. et al, FEBS Lett, 1995, \"A novel approach for expression cloning of small GTPases: identification, tissue distribution and chromosome mapping of the human homolog of rheb\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8543055/","biology":"Small GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. In response to nutrients, growth factors or amino acids, specifically activates the protein kinase activity of MTOR, the catalytic component of the mTORC1 complex: acts by causing a conformational change that allows the alignment of residues in the active site of MTOR, thereby enhancing the phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). RHEB is also required for localisation of the TSC-TBC complex to lysosomal membranes. In response to starvation, RHEB is inactivated by the TSC-TBC complex, preventing activation of mTORC1. Has low intrinsic GTPase activity. Location: Endomembrane system; Lysosome membrane; Golgi apparatus membrane; Endoplasmic reticulum membrane (UniProt). Locus 7q36.1 (HGNC).","whereFound":["Renal cell carcinoma: CIViC evidence names this disease"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/rheb/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}],"cancer":[{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}]}}