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Gene Review

RORA  -  RAR-related orphan receptor A

Homo sapiens

Synonyms: NR1F1, Nuclear receptor ROR-alpha, Nuclear receptor RZR-alpha, Nuclear receptor subfamily 1 group F member 1, ROR1, ...
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Disease relevance of RORA


High impact information on RORA

  • Intriguingly, disruption of filopodia formation by suppressing the expression of either Ror2 or filamin A inhibits Wnt5a-induced cell migration, indicating that Ror2-mediated filopodia formation is essential for Wnt5a-induced cell migration [5].
  • The receptor tyrosine kinase Ror2 plays important roles in developmental morphogenesis [5].
  • Ror2-mediated cell migration requires the extracellular cysteine-rich domain (CRD), which is the binding site for Wnt5a, and the cytoplasmic proline-rich domain (PRD) of Ror2 [5].
  • In the present study the function of retinoic acid receptor-related orphan receptor (ROR) alpha in bone metabolism has been examined [6].
  • ROR(alpha) (NR1F1) and Reverb(alpha) (NR1D1) are two members of this family whose biological functions are largely unknown [7].

Chemical compound and disease context of RORA

  • Recently, the participation of nuclear signalling via estrogen as well as RZR/ROR receptors in oncostatic action of melatonin on the breast cancer has been widely discussed [8].
  • The aim of present study was to investigate effects of melatonin, the selective ligand for nuclear RZR/ROR receptors - CGP 52608, and methotrexate on growth of murine 16/C breast cancer cells [8].

Biological context of RORA


Anatomical context of RORA

  • Here, we analyzed the expression of the three members of the retinoid-like orphan receptor (ROR) nuclear receptor subfamily during adipocyte differentiation [11].
  • We have shown that the thiazolidinedione derivative CGP 52608, the specific ROR alpha ligand and activator, reduces the ability of DU 145 cells to invade a reconstituted basement membrane (Matrigel) [3].
  • In the present study we first demonstrate that hypoxia increases the amount of Rora transcripts in a wide panel of cell lines derived from diverse tissues [4].
  • Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration [5].
  • We show, using genetically different or manipulated cultured cells, that Ror2 is critical for Wnt5a-induced, but not Wnt3a-induced, cell migration [5].

Associations of RORA with chemical compounds

  • Retinoic acid receptor-related orphan receptor-alpha (RORalpha) (NR1F1) is an orphan nuclear receptor with a potential role in metabolism [12].
  • The two subtypes of retinoid Z receptor (RZR alpha and beta) and the three splicing variants of retinoid orphan receptor (ROR alpha 1, alpha 2, and alpha 3) form a subfamily within the superfamily of nuclear hormone receptors [10].
  • We examined the effects of various tumor promoters on transcription mediated by several nuclear receptors (RAR, TR, and ROR) by using thymidine kinase promoter-based reporter systems [13].
  • We have also achieved enhanced production of IL-2 and IL-6 using CGP 52608, a specific ligand of the putative nuclear melatonin receptor RZR/ROR, raising the possibility of direct effects of melatonin on gene regulation in both Th1 cells and monocytes [14].
  • A high-resolution X-ray crystal structure of the retinoic acid receptor-related orphan receptor (RORalpha; NR1F1), which reveals a molecule of cholesterol within the ligand binding pocket, is a breakthrough in functional analysis of this orphan nuclear receptor [15].

Other interactions of RORA

  • In this study, we demonstrate that the 730 kb retinoic acid receptor-related orphan receptor alpha (RORA) gene is derived from the middle of the FRA15A (15q22.2) CFS [1].
  • Overexpression of HIF-1alpha increased the activity of the Rora promoter through the HRE [4].
  • Taken together, our data reveal Rora as a new HIF-1 target gene [4].


  1. RORA, a large common fragile site gene, is involved in cellular stress response. Zhu, Y., McAvoy, S., Kuhn, R., Smith, D.I. Oncogene (2006) [Pubmed]
  2. RAR-related orphan receptor A isoform 1 (RORa1) is disrupted by a balanced translocation t(4;15)(q22.3;q21.3) associated with severe obesity. Klar, J., Asling, B., Carlsson, B., Ulvsbäck, M., Dellsén, A., Ström, C., Rhedin, M., Forslund, A., Annerén, G., Ludvigsson, J.F., Dahl, N. Eur. J. Hum. Genet. (2005) [Pubmed]
  3. Role of the orphan nuclear receptor ROR alpha in the control of the metastatic behavior of androgen-independent prostate cancer cells. Moretti, R.M., Marelli, M.M., Motta, M., Limonta, P. Oncol. Rep. (2002) [Pubmed]
  4. The gene encoding human retinoic acid-receptor-related orphan receptor alpha is a target for hypoxia-inducible factor 1. Chauvet, C., Bois-Joyeux, B., Berra, E., Pouyssegur, J., Danan, J.L. Biochem. J. (2004) [Pubmed]
  5. Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration. Nishita, M., Yoo, S.K., Nomachi, A., Kani, S., Sougawa, N., Ohta, Y., Takada, S., Kikuchi, A., Minami, Y. J. Cell Biol. (2006) [Pubmed]
  6. In vitro and in vivo evidence for orphan nuclear receptor RORalpha function in bone metabolism. Meyer, T., Kneissel, M., Mariani, J., Fournier, B. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. Identification of Reverb(alpha) as a novel ROR(alpha) target gene. Delerive, P., Chin, W.W., Suen, C.S. J. Biol. Chem. (2002) [Pubmed]
  8. Growth-inhibitory action of melatonin and thiazolidinedione derivative CGP 52608 on murine 16/C breast cancer cells. Winczyk, K., Lawnicka, H., Pawlikowski, M., Kunert-Radek, J., Karasek, M. Neuro Endocrinol. Lett. (2006) [Pubmed]
  9. The orphan nuclear receptor ROR alpha (RORA) maps to a conserved region of homology on human chromosome 15q21-q22 and mouse chromosome 9. Giguère, V., Beatty, B., Squire, J., Copeland, N.G., Jenkins, N.A. Genomics (1995) [Pubmed]
  10. The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. Steinhilber, D., Brungs, M., Werz, O., Wiesenberg, I., Danielsson, C., Kahlen, J.P., Nayeri, S., Schräder, M., Carlberg, C. J. Biol. Chem. (1995) [Pubmed]
  11. Induction of the nuclear orphan receptor RORgamma during adipocyte differentiation of D1 and 3T3-L1 cells. Austin, S., Medvedev, A., Yan, Z.H., Adachi, H., Hirose, T., Jetten, A.M. Cell Growth Differ. (1998) [Pubmed]
  12. Identification of the human ApoAV gene as a novel RORalpha target gene. Lind, U., Nilsson, T., McPheat, J., Strömstedt, P.E., Bamberg, K., Balendran, C., Kang, D. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. Enhancing effect of tumor promoters, phorbol esters and teleocidins on nuclear receptor-mediated transcription. Fukasawa, H., Yamaguchi, M., Hashimoto, Y., Endo, Y., Shudo, K. Biol. Pharm. Bull. (2000) [Pubmed]
  14. Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. Garcia-Mauriño, S., Gonzalez-Haba, M.G., Calvo, J.R., Rafii-El-Idrissi, M., Sanchez-Margalet, V., Goberna, R., Guerrero, J.M. J. Immunol. (1997) [Pubmed]
  15. RORalpha: an orphan nuclear receptor on a high-cholesterol diet. Willson, T.M. Structure (Camb.) (2002) [Pubmed]
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