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Gene Review

ESR2  -  estrogen receptor 2 (ER beta)

Homo sapiens

Synonyms: ER-BETA, ER-beta, ESR-BETA, ESRB, ESTRB, ...
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Disease relevance of ESR2


Psychiatry related information on ESR2


High impact information on ESR2


Chemical compound and disease context of ESR2


Biological context of ESR2

  • However an association was found at the ESR2 locus with the heterozygous genotype of the G1082A polymorphism and AN but not with any of the other ESR2 polymorphisms analysed [6].
  • MATERIALS AND METHODS: In the Rotterdam study, a prospective population-based cohort of elderly white individuals, we studied six single nucleotide polymorphisms (SNPs) in ESR2 (n = 6343, 60% women) [21].
  • Previously genetic variation in the estrogen receptor 2 gene (ESR2) has been studied, however no strong evidence of association with AN has been found [6].
  • HSA showed that ESR2 haplotype 1 homozygote women had 2.6% thinner cortices, 1.0% increased neck width, and 4.3% higher bone instability (buckling ratios) [21].
  • Genotype pattern tracking in extreme phenotypes and multi-locus analysis using Sumstat and PM algorithms provided significant evidences of genetic interaction between FSHR, ESR1 and ESR2 markers in relation to COS outcome (P = 0.0015) [22].

Anatomical context of ESR2


Associations of ESR2 with chemical compounds

  • These results suggest that ESR2 1082G>A genotype may influence LDL-C levels in women with abundant estrogen levels, due to either endogenous or exogenous sources [27].
  • Some associations were much more prominent in specific races/ethnicities; Chinese women had statistically significant relations between ESR2 rs1256030 and HDL cholesterol, lumbar spine BMD, hip BMD, and metabolic syndrome [28].
  • It shows lesser enhancement of ERbeta transcriptional activity and has no influence on the transcriptional activity of other nuclear hormone receptors (progesterone receptor, glucocorticoid receptor, thyroid hormone receptor, or retinoic acid receptor) or on the basal activity of ERs [29].
  • Immunofluorescence microscopy showed that ER beta protein was present in glycoprotein (GP) IIb(+) megakaryocytes and the HEL megakaryocytic cell line in a predominantly cytoplasmic location [3].
  • The ER-beta variant protein is predicted to lack part of the hormone-binding domain and may bind E2 with lower affinity than the wild-type ER-beta protein [30].

Physical interactions of ESR2


Co-localisations of ESR2


Regulatory relationships of ESR2


Other interactions of ESR2


Analytical, diagnostic and therapeutic context of ESR2


  1. Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Gold, B., Kalush, F., Bergeron, J., Scott, K., Mitra, N., Wilson, K., Ellis, N., Huang, H., Chen, M., Lippert, R., Halldorsson, B.V., Woodworth, B., White, T., Clark, A.G., Parl, F.F., Broder, S., Dean, M., Offit, K. Cancer Res. (2004) [Pubmed]
  2. Polymorphisms of estrogen receptor beta gene are associated with hypospadias. Beleza-Meireles, A., Omrani, D., Kockum, I., Frisén, L., Lagerstedt, K., Nordenskjöld, A. J. Endocrinol. Invest. (2006) [Pubmed]
  3. Human megakaryocytes and platelets contain the estrogen receptor beta and androgen receptor (AR): testosterone regulates AR expression. Khetawat, G., Faraday, N., Nealen, M.L., Vijayan, K.V., Bolton, E., Noga, S.J., Bray, P.F. Blood (2000) [Pubmed]
  4. CYP1B1 gene polymorphisms have higher risk for endometrial cancer, and positive correlations with estrogen receptor alpha and estrogen receptor beta expressions. Sasaki, M., Tanaka, Y., Kaneuchi, M., Sakuragi, N., Dahiya, R. Cancer Res. (2003) [Pubmed]
  5. Estrogen receptor alpha and beta heterodimers exert unique effects on estrogen- and tamoxifen-dependent gene expression in human U2OS osteosarcoma cells. Monroe, D.G., Secreto, F.J., Subramaniam, M., Getz, B.J., Khosla, S., Spelsberg, T.C. Mol. Endocrinol. (2005) [Pubmed]
  6. Variation in the ESR1 and ESR2 genes and genetic susceptibility to anorexia nervosa. Eastwood, H., Brown, K.M., Markovic, D., Pieri, L.F. Mol. Psychiatry (2002) [Pubmed]
  7. Estrogen receptor beta gene variants are associated with increased risk of Alzheimer's disease in women. Pirskanen, M., Hiltunen, M., Mannermaa, A., Helisalmi, S., Lehtovirta, M., Hänninen, T., Soininen, H. Eur. J. Hum. Genet. (2005) [Pubmed]
  8. Role of estrogen receptor-alpha in pharmacogenetics of estrogen action. Herrington, D.M. Curr. Opin. Lipidol. (2003) [Pubmed]
  9. No evidence to support an association between the oestrogen receptor beta gene and bipolar disorder. Kealey, C., Reynolds, A., Mynett-Johnson, L., Claffey, E., McKeon, P. Psychiatr. Genet. (2001) [Pubmed]
  10. Estrogen receptor gene expression in relation to neuropsychiatric disorders. Ostlund, H., Keller, E., Hurd, Y.L. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  11. Antisense oligodeoxynucleotides for estrogen receptor-beta and alpha attenuate estradiol's modulation of affective and sexual behavior, respectively. Walf, A.A., Ciriza, I., Garcia-Segura, L.M., Frye, C.A. Neuropsychopharmacology (2008) [Pubmed]
  12. Mechanisms of estrogen action. Nilsson, S., Mäkelä, S., Treuter, E., Tujague, M., Thomsen, J., Andersson, G., Enmark, E., Pettersson, K., Warner, M., Gustafsson, J.A. Physiol. Rev. (2001) [Pubmed]
  13. Reflections on the discovery and significance of estrogen receptor beta. Koehler, K.F., Helguero, L.A., Haldosén, L.A., Warner, M., Gustafsson, J.A. Endocr. Rev. (2005) [Pubmed]
  14. Estrogen receptor mutations in human disease. Herynk, M.H., Fuqua, S.A. Endocr. Rev. (2004) [Pubmed]
  15. Basic guide to the mechanisms of antiestrogen action. MacGregor, J.I., Jordan, V.C. Pharmacol. Rev. (1998) [Pubmed]
  16. Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D. Ström, A., Hartman, J., Foster, J.S., Kietz, S., Wimalasena, J., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  17. Estrogen receptor beta protein in human breast cancer: correlation with clinical tumor parameters. Fuqua, S.A., Schiff, R., Parra, I., Moore, J.T., Mohsin, S.K., Osborne, C.K., Clark, G.M., Allred, D.C. Cancer Res. (2003) [Pubmed]
  18. Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer. Hopp, T.A., Weiss, H.L., Parra, I.S., Cui, Y., Osborne, C.K., Fuqua, S.A. Clin. Cancer Res. (2004) [Pubmed]
  19. Differential expression of steroid receptors in prostate tissues before and after radiation therapy for prostatic adenocarcinoma. Torlakovic, E., Lilleby, W., Berner, A., Torlakovic, G., Chibbar, R., Furre, T., Fosså, S.D. Int. J. Cancer (2005) [Pubmed]
  20. Clinical significance of estrogen receptor beta in breast cancer. Saji, S., Hirose, M., Toi, M. Cancer Chemother. Pharmacol. (2005) [Pubmed]
  21. Estrogen receptor beta (ESR2) polymorphisms in interaction with estrogen receptor alpha (ESR1) and insulin-like growth factor I (IGF1) variants influence the risk of fracture in postmenopausal women. Rivadeneira, F., van Meurs, J.B., Kant, J., Zillikens, M.C., Stolk, L., Beck, T.J., Arp, P., Schuit, S.C., Hofman, A., Houwing-Duistermaat, J.J., van Duijn, C.M., van Leeuwen, J.P., Pols, H.A., Uitterlinden, A.G. J. Bone Miner. Res. (2006) [Pubmed]
  22. Human controlled ovarian hyperstimulation outcome is a polygenic trait. de Castro, F., Morón, F.J., Montoro, L., Galán, J.J., Hernández, D.P., Padilla, E.S., Ramírez-Lorca, R., Real, L.M., Ruiz, A. Pharmacogenetics (2004) [Pubmed]
  23. Regulation of endogenous gene expression in human non-small cell lung cancer cells by estrogen receptor ligands. Hershberger, P.A., Vasquez, A.C., Kanterewicz, B., Land, S., Siegfried, J.M., Nichols, M. Cancer Res. (2005) [Pubmed]
  24. Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Järvinen, T.A., Pelto-Huikko, M., Holli, K., Isola, J. Am. J. Pathol. (2000) [Pubmed]
  25. Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered ER and PR isoform expression. Jazaeri, A.A., Nunes, K.J., Dalton, M.S., Xu, M., Shupnik, M.A., Rice, L.W. Oncogene (2001) [Pubmed]
  26. Transrepression of estrogen receptor beta signaling by nuclear factor-kappab in ovarian granulosa cells. Chu, S., Nishi, Y., Yanase, T., Nawata, H., Fuller, P.J. Mol. Endocrinol. (2004) [Pubmed]
  27. Estrogen receptor 2 and progesterone receptor gene polymorphisms and lipid levels in women with different hormonal status. Almeida, S., Franken, N., Zandoná, M.R., Osório-Wender, M.C., Hutz, M.H. Pharmacogenomics J. (2005) [Pubmed]
  28. Sex steroid hormone pathway genes and health-related measures in women of 4 races/ethnicities: the Study of Women's Health Across the Nation (SWAN). Sowers, M.R., Wilson, A.L., Karvonen-Gutierrez, C.A., Kardia, S.R. Am. J. Med. (2006) [Pubmed]
  29. Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity. Martini, P.G., Delage-Mourroux, R., Kraichely, D.M., Katzenellenbogen, B.S. Mol. Cell. Biol. (2000) [Pubmed]
  30. Expression of estrogen receptor beta messenger RNA variant in breast cancer. Vladusic, E.A., Hornby, A.E., Guerra-Vladusic, F.K., Lupu, R. Cancer Res. (1998) [Pubmed]
  31. Comparison of estrogen receptor alpha and beta subtypes based on comparative molecular field analysis (CoMFA). Xing, L., Welsh, W.J., Tong, W., Perkins, R., Sheehan, D.M. SAR and QSAR in environmental research. (1999) [Pubmed]
  32. Identification and characterization of a novel factor that regulates quinone reductase gene transcriptional activity. Montano, M.M., Wittmann, B.M., Bianco, N.R. J. Biol. Chem. (2000) [Pubmed]
  33. Isoform-selective interactions between estrogen receptors and steroid receptor coactivators promoted by estradiol and ErbB-2 signaling in living cells. Bai, Y., Giguére, V. Mol. Endocrinol. (2003) [Pubmed]
  34. Terpenoids found in the umbelliferae family act as agonists/antagonists for ER(alpha) and ERbeta: differential transcription activity between ferutinine-liganded ER(alpha) and ERbeta. Ikeda, K., Arao, Y., Otsuka, H., Nomoto, S., Horiguchi, H., Kato, S., Kayama, F. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  35. Multiplexed molecular interactions of nuclear receptors using fluorescent microspheres. Iannone, M.A., Consler, T.G., Pearce, K.H., Stimmel, J.B., Parks, D.J., Gray, J.G. Cytometry. (2001) [Pubmed]
  36. Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats. Mazzucco, C.A., Lieblich, S.E., Bingham, B.I., Williamson, M.A., Viau, V., Galea, L.A. Neuroscience (2006) [Pubmed]
  37. Rapid estrogen-induced phosphorylation of the SRC-3 coactivator occurs in an extranuclear complex containing estrogen receptor. Zheng, F.F., Wu, R.C., Smith, C.L., O'Malley, B.W. Mol. Cell. Biol. (2005) [Pubmed]
  38. Differential modulation of DNA conformation by estrogen receptors alpha and beta. Schultz, J.R., Loven, M.A., Melvin, V.M., Edwards, D.P., Nardulli, A.M. J. Biol. Chem. (2002) [Pubmed]
  39. The Ah receptor inhibits estrogen-induced estrogen receptor beta in breast cancer cells. Kietz, S., Thomsen, J.S., Matthews, J., Pettersson, K., Ström, A., Gustafsson, J.A. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  40. Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism. Shiau, A.K., Barstad, D., Radek, J.T., Meyers, M.J., Nettles, K.W., Katzenellenbogen, B.S., Katzenellenbogen, J.A., Agard, D.A., Greene, G.L. Nat. Struct. Biol. (2002) [Pubmed]
  41. Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-alpha and estrogen receptor-beta. Montano, M.M., Jaiswal, A.K., Katzenellenbogen, B.S. J. Biol. Chem. (1998) [Pubmed]
  42. Estrogen receptor isoform-specific induction of progesterone receptors in human osteoblasts. Rickard, D.J., Waters, K.M., Ruesink, T.J., Khosla, S., Katzenellenbogen, J.A., Katzenellenbogen, B.S., Riggs, B.L., Spelsberg, T.C. J. Bone Miner. Res. (2002) [Pubmed]
  43. The modulation of aromatase and estrogen receptor alpha in cultured human dermal papilla cells by dexamethasone: a novel mechanism for selective action of estrogen via estrogen receptor beta? Thornton, M.J., Nelson, L.D., Taylor, A.H., Birch, M.P., Laing, I., Messenger, A.G. J. Invest. Dermatol. (2006) [Pubmed]
  44. Estrogen receptor beta isoform-specific induction of transforming growth factor beta-inducible early gene-1 in human osteoblast cells: an essential role for the activation function 1 domain. Hawse, J.R., Subramaniam, M., Monroe, D.G., Hemmingsen, A.H., Ingle, J.N., Khosla, S., Oursler, M.J., Spelsberg, T.C. Mol. Endocrinol. (2008) [Pubmed]
  45. Human splicing factor SPF45 (RBM17) confers broad multidrug resistance to anticancer drugs when overexpressed--a phenotype partially reversed by selective estrogen receptor modulators. Perry, W.L., Shepard, R.L., Sampath, J., Yaden, B., Chin, W.W., Iversen, P.W., Jin, S., Lesoon, A., O'Brien, K.A., Peek, V.L., Rolfe, M., Shyjan, A., Tighe, M., Williamson, M., Krishnan, V., Moore, R.E., Dantzig, A.H. Cancer Res. (2005) [Pubmed]
  46. Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest. Paruthiyil, S., Parmar, H., Kerekatte, V., Cunha, G.R., Firestone, G.L., Leitman, D.C. Cancer Res. (2004) [Pubmed]
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