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Gene Review

RORC  -  RAR-related orphan receptor C

Homo sapiens

Synonyms: NR1F3, Nuclear receptor ROR-gamma, Nuclear receptor RZR-gamma, Nuclear receptor subfamily 1 group F member 3, RORG, ...
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Disease relevance of RORC

  • PURPOSE: To perform a randomized three-arm comparison of tamoxifen (TAM; 20 mg/d) and two separate doses of toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d [TOR200]) in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer [1].
  • CONCLUSION: The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM [1].
  • Overexpression/selection using the toxic nucleoside tubercidin similarly yielded the TOR (toxic nucleoside resistance) locus, as well as a new locus (TUB2) conferring collateral hypersensitivity to allopurinol [2].
  • The TOR (target of rapamycin) pathway is an evolutionarily conserved signaling module regulating cell growth (accumulation of mass) in response to a variety of environmental cues such as nutrient availability, hypoxia, DNA damage and osmotic stress [3].
  • Two peaks of association here contain the psoriasis candidate genes SLC9A3R (solute carrier family 9, isoform 3 regulatory factor), NAT9 (N-acetyltransferase superfamily), and RAPTOR (rapamycin (TOR)) [4].

High impact information on RORC

  • TOR, a central controller of cell growth [5].
  • Over the past 10 years the signal transduction networks for p53, IGF-1-AKT, and TOR pathways have been assembled in worms, flies, and mammals, and their functions elucidated [6].
  • The TOR kinases also regulate responses to nutrients, including sporulation, autophagy, mating, and ribosome biogenesis [7].
  • In summary, our results reveal that the TOR cascade plays a prominent role in regulating transcription in response to nutrients in addition to its known roles in regulating translation, ribosome biogenesis, and amino acid permease stability [7].
  • The TOR signaling cascade regulates gene expression in response to nutrients [7].

Biological context of RORC


Anatomical context of RORC

  • RORC may form heterodimers with peroxisome-proliferator activated receptor gamma, it is expressed at high levels in skeletal muscle, and expression is induced in adipocytes during differentiation [8].
  • Fourteen of these mutants show a gain of function: they induce rapamycin-sensitive oncogenic transformation of chicken embryo fibroblasts, constitutively activate Akt and TOR-mediated signaling, and show enhanced lipid kinase activity [11].
  • In the budding yeast Saccharomyces cerevisiae and in human T cells, rapamycin forms a complex with FKBP12 that inhibits cell cycle progression by inhibition of the TOR kinases [12].
  • The TOR proteins promote cell cycle progression in yeast and human cells by regulating translation and polarization of the actin cytoskeleton [10].
  • Given the unsurpassed resources available to yeast researchers, this simple eukaryote continues to contribute to our understanding of eukaryotic cell growth in general and TOR function in particular.Oncogene (2006) 25, 6392-6415. doi:10.1038/sj.onc.1209884 [13].

Associations of RORC with chemical compounds

  • The retinoid-related orphan receptor gamma (RORC) is a member of the nuclear hormone superfamily which maps to the 1q21-q23 region [8].
  • The TOR protein is a phosphoinositide kinase-related kinase widely conserved among eukaryotes [9].
  • Interaction between FKBP12-rapamycin and TOR involves a conserved serine residue [14].
  • Herein we demonstrate that raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs to be required for amino acid- and mTOR-dependent regulation of these mTOR substrates in vivo [15].
  • Taking advantage of its antifungal property, the molecular Target Of Rapamycin, TOR, was first described in the budding yeast Saccharomyces cerevisiae [13].

Analytical, diagnostic and therapeutic context of RORC

  • METHODS: In this study we examined the feasibility of monitoring TOR inhibitor-based immunosuppression by assessment of the phosphorylation status at the Thr(389) site of the p70S6 kinase in peripheral blood mononuclear cells (PBMCs) [16].
  • The identification of target genes subject to regulation by TOR has provided a platform for the dissection of the signaling events downstream of the TOR kinases [17].
  • TOR inhibitors and cardiac allograft vasculopathy: is inhibition of intimal thickening an adequate surrogate of benefit [18]?
  • TOR of the cell cycle: Are there important implications for diabetics in the era of the drug-eluting stent [19]?
  • TOR was 0.73 +/- 0.06 and 0.52 +/- 0.02 mmol min-1 (P < 0.05) in the basal state, 0.33 +/- 0.04 and 0.30 +/- 0.02 at an insulin level of 50 mU l-1 and 0.32 +/- 0.08 and 0.24 +/- 0.02 at an insulin level of 100 mU l-1, in the COPD and control groups, respectively [20].


  1. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. Hayes, D.F., Van Zyl, J.A., Hacking, A., Goedhals, L., Bezwoda, W.R., Mailliard, J.A., Jones, S.E., Vogel, C.L., Berris, R.F., Shemano, I. J. Clin. Oncol. (1995) [Pubmed]
  2. Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by overexpression/selection. Cotrim, P.C., Garrity, L.K., Beverley, S.M. J. Biol. Chem. (1999) [Pubmed]
  3. Stress and mTORture signaling. Reiling, J.H., Sabatini, D.M. Oncogene (2006) [Pubmed]
  4. Investigation of the chromosome 17q25 PSORS2 locus in atopic dermatitis. Morar, N., Bowcock, A.M., Harper, J.I., Cookson, W.O., Moffatt, M.F. J. Invest. Dermatol. (2006) [Pubmed]
  5. TOR, a central controller of cell growth. Schmelzle, T., Hall, M.N. Cell (2000) [Pubmed]
  6. Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Levine, A.J., Feng, Z., Mak, T.W., You, H., Jin, S. Genes Dev. (2006) [Pubmed]
  7. The TOR signaling cascade regulates gene expression in response to nutrients. Cardenas, M.E., Cutler, N.S., Lorenz, M.C., Di Como, C.J., Heitman, J. Genes Dev. (1999) [Pubmed]
  8. Molecular screening and association studies of retinoid-related orphan receptor gamma (RORC): a positional and functional candidate for type 2 diabetes. Wang, H., Chu, W., Das, S.K., Zheng, Z., Hasstedt, S.J., Elbein, S.C. Mol. Genet. Metab. (2003) [Pubmed]
  9. Schizosaccharomyces pombe AGC family kinase Gad8p forms a conserved signaling module with TOR and PDK1-like kinases. Matsuo, T., Kubo, Y., Watanabe, Y., Yamamoto, M. EMBO J. (2003) [Pubmed]
  10. Protein kinase activity and identification of a toxic effector domain of the target of rapamycin TOR proteins in yeast. Alarcon, C.M., Heitman, J., Cardenas, M.E. Mol. Biol. Cell (1999) [Pubmed]
  11. Rare cancer-specific mutations in PIK3CA show gain of function. Gymnopoulos, M., Elsliger, M.A., Vogt, P.K. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  12. Rapamycin blocks sexual development in fission yeast through inhibition of the cellular function of an FKBP12 homolog. Weisman, R., Finkelstein, S., Choder, M. J. Biol. Chem. (2001) [Pubmed]
  13. Cell growth control: little eukaryotes make big contributions. De Virgilio, C., Loewith, R. Oncogene (2006) [Pubmed]
  14. Interaction between FKBP12-rapamycin and TOR involves a conserved serine residue. Stan, R., McLaughlin, M.M., Cafferkey, R., Johnson, R.K., Rosenberg, M., Livi, G.P. J. Biol. Chem. (1994) [Pubmed]
  15. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. Nojima, H., Tokunaga, C., Eguchi, S., Oshiro, N., Hidayat, S., Yoshino, K., Hara, K., Tanaka, N., Avruch, J., Yonezawa, K. J. Biol. Chem. (2003) [Pubmed]
  16. Biochemical monitoring of mTOR inhibitor-based immunosuppression following kidney transplantation: a novel approach for tailored immunosuppressive therapy. Hartmann, B., Schmid, G., Graeb, C., Bruns, C.J., Fischereder, M., Jauch, K.W., Heeschen, C., Guba, M. Kidney Int. (2005) [Pubmed]
  17. Nutrient signaling through TOR kinases controls gene expression and cellular differentiation in fungi. Rohde, J.R., Cardenas, M.E. Curr. Top. Microbiol. Immunol. (2004) [Pubmed]
  18. TOR inhibitors and cardiac allograft vasculopathy: is inhibition of intimal thickening an adequate surrogate of benefit? Mehra, M.R., Uber, P.A. J. Heart Lung Transplant. (2003) [Pubmed]
  19. TOR of the cell cycle: Are there important implications for diabetics in the era of the drug-eluting stent? Carter, A.J. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. (2004) [Pubmed]
  20. Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease. Jakobsson, P., Jorfeldt, L., von Schenck, H. Clinical physiology (Oxford, England) (1995) [Pubmed]
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