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Gene Review

NR0B1  -  nuclear receptor subfamily 0, group B,...

Homo sapiens

Synonyms: AHC, AHCH, AHX, DAX-1, DAX1, ...
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Disease relevance of NR0B1


Psychiatry related information on NR0B1

  • We report on deletion mapping and X inactivation analysis of a gene for X linked non-specific mental retardation (MRX) at Xp21.3-Xp22.11, on the basis of molecular studies in two families with Xp microdeletions involving the DAX-1 gene [5].
  • The authors conclude that the AHC grant program has been successful in generating external research funds (primarily National Institutes of Health) and publications; stimulating risk-taking; and developing interdisciplinary and intercollegiate collaboration [6].
  • A DSS can use these guideline statements in multiple ways, including: (1) as inputs for determining preferred alternatives in decision-making, and (2) as a way to provide targeted commentaries in the clinical information system [7].

High impact information on NR0B1

  • Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene [8].
  • The identification of male individuals deleted for DSS suggests that this locus is not required for testis differentiation [9].
  • We have named this locus DSS (Dosage Sensitive Sex reversal) and localized it to a 160 kilobase region of chromosome Xp21, adjacent to the adrenal hypoplasia congenita locus [9].
  • Here we show that DAX-1 binds DNA and acts as a powerful transcriptional repressor of StAR gene expression, leading to a drastic decrease in steroid production [10].
  • DAX-1 is an unusual member of the nuclear-receptor superfamily of transcription factors which contains no canonical zinc-finger or any other known DNA-binding motif [10].

Chemical compound and disease context of NR0B1


Biological context of NR0B1

  • DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1; NR0B1) is an orphan nuclear receptor that plays an important role in the development and functioning of the adrenal gland and hypothalamic-pituitary gonadal axis [15].
  • Over-expression of NR0B1 results in sex reversal in mice and duplication of the 160kb DSS locus in human patients results in a sex-reversed phenotype (XY females) [1].
  • We show that DAX-1 potently inhibits ligand-dependent transcriptional activation as well as the interaction between the N- and C-terminal activation domains of AR [16].
  • Identification of a novel missense mutation that is as damaging to DAX-1 repressor function as a nonsense mutation [17].
  • Transient transfection assays demonstrated that both mutations resulted in a severe loss of DAX-1 repressor activity [17].

Anatomical context of NR0B1


Associations of NR0B1 with chemical compounds

  • These results implicate novel inhibitory mechanisms of DAX-1 action with particular relevance for the modulation of androgen-dependent gene transcription in the male reproductive system [16].
  • DAX-1 functions as a global negative regulator of steroid hormone production [22].
  • The expression of DAX-1 protein was slightly inhibited by 10(-6) m oestradiol (E2) at 6 h but enhanced by 10(-6) m dihydrotestosterone (DHT) at 48 h [23].
  • The DAX-1 product acts as a dominant negative regulator of transcription mediated by the retinoic acid receptor [24].
  • We provide in vitro and in vivo evidence that DAX-1 binds to DNA hairpin structures [10].

Physical interactions of NR0B1

  • We provide evidence for direct interactions of the two receptors that involve the N-terminal repeat domain of DAX-1 and the C-terminal ligand-binding and activation domain of AR [16].
  • A luciferase assay also indicated that these two cofactors enhanced Ad4BP/SF-1 transactivation.Dosage-sensitive sex reversal (DAX-1) interacts with and thus inhibits Ad4BP/SF-1 transactivation [25].
  • Naturally occurring mutants of the DAX-1 gene fail to interact with Alien and have lost silencing function [26].
  • We have discovered that the orphan receptor DAX-1 (NROB1) interacts with the estrogen receptors ERalpha and ERbeta [27].

Enzymatic interactions of NR0B1

  • The DAX-1 gene was entirely deleted in a 3rd patient as well as in a 4th with the additional feature of glycerol kinase deficiency [28].

Regulatory relationships of NR0B1


Other interactions of NR0B1

  • Inhibition of androgen receptor (AR) function by the reproductive orphan nuclear receptor DAX-1 [16].
  • Recent studies have demonstrated that DAX-1 and COUP-TFII negatively regulate adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1)-dependent transcription of steroidogenic enzymes in experimental animals [19].
  • No significant correlations were detected between DAX-1 immunoreactivity and amounts of aromatase mRNA [22].
  • There was a statistically significant positive correlation between DAX-1 and ERalpha (P = 0.006) and ERbeta LI (P < 0.001) [22].
  • These findings suggest that DAX-1 may inhibit the proliferation and progression of endometrial carcinoma through inhibition of estrogenic actions, possibly by interacting with ER present in carcinoma cells, rather than regulating in situ steroidogenesis [22].

Analytical, diagnostic and therapeutic context of NR0B1


  1. NR0B1A: an alternatively spliced form of NR0B1. Ho, J., Zhang, Y.H., Huang, B.L., McCabe, E.R. Mol. Genet. Metab. (2004) [Pubmed]
  2. Somatic mutational analysis of DAX1 in testes from men with idiopathic azoospermia. Mantovani, G., Mancini, M., Gazzano, G., Spada, A., Colpi, G.M., Beck-Peccoz, P., Persani, L. Fertil. Steril. (2005) [Pubmed]
  3. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience. Lin, L., Gu, W.X., Ozisik, G., To, W.S., Owen, C.J., Jameson, J.L., Achermann, J.C. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  4. Expression of an orphan nuclear receptor DAX-1 in human pituitary adenomas. Ikuyama, S., Mu, Y.M., Ohe, K., Nakagaki, H., Fukushima, T., Takayanagi, R., Nawata, H. Clin. Endocrinol. (Oxf) (1998) [Pubmed]
  5. Deletion mapping and X inactivation analysis of a non-specific mental retardation gene at Xp21.3-Xp22.11. Muroya, K., Kinoshita, E., Kamimaki, T., Matsuo, N., Yorifugi, T., Ogata, T. J. Med. Genet. (1999) [Pubmed]
  6. Investing in research: the impact of one academic health center's research grant program. Paller, M.S., Cerra, F.B. Academic medicine : journal of the Association of American Medical Colleges. (2006) [Pubmed]
  7. Use of declarative statements in creating and maintaining computer-interpretable knowledge bases for guideline-based care. Tu, S.W., Hrabak, K.M., Campbell, J.R., Glasgow, J., Nyman, M.A., McClure, R., McClay, J., Abarbanel, R., Mansfield, J.G., Martins, S.M., Goldstein, M.K., Musen, M.A. AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium (2006) [Pubmed]
  8. Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene. Merke, D.P., Tajima, T., Baron, J., Cutler, G.B. N. Engl. J. Med. (1999) [Pubmed]
  9. A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Bardoni, B., Zanaria, E., Guioli, S., Floridia, G., Worley, K.C., Tonini, G., Ferrante, E., Chiumello, G., McCabe, E.R., Fraccaro, M. Nat. Genet. (1994) [Pubmed]
  10. DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis. Zazopoulos, E., Lalli, E., Stocco, D.M., Sassone-Corsi, P. Nature (1997) [Pubmed]
  11. Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors: possible implications in steroidogenesis. Shibata, H., Ikeda, Y., Mukai, T., Morohashi, K., Kurihara, I., Ando, T., Suzuki, T., Kobayashi, S., Murai, M., Saito, I., Saruta, T. Mol. Genet. Metab. (2001) [Pubmed]
  12. Glycerol metabolism and the determination of triglycerides--clinical, biochemical and molecular findings in six subjects. Hellerud, C., Burlina, A., Gabelli, C., Ellis, J.R., Nyholm, P.G., Lindstedt, S. Clin. Chem. Lab. Med. (2003) [Pubmed]
  13. DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis. Reincke, M., Beuschlein, F., Lalli, E., Arlt, W., Vay, S., Sassone-Corsi, P., Allolio, B. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  14. Phase II evaluation of dibromodulcitol and actinomycin D, hydroxyurea, and cyclophosphamide in previously untreated patients with malignant melanoma. Amato, D.A., Bruckner, H., Guerry, D., Ash, A., Falkson, G., Borden, E.C., Creech, R.H., Savlov, E.D., Cunningham, T.J. Investigational new drugs. (1987) [Pubmed]
  15. Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing. Hossain, A., Li, C., Saunders, G.F. Mol. Endocrinol. (2004) [Pubmed]
  16. Inhibition of androgen receptor (AR) function by the reproductive orphan nuclear receptor DAX-1. Holter, E., Kotaja, N., Mäkela, S., Strauss, L., Kietz, S., Jänne, O.A., Gustafsson, J.A., Palvimo, J.J., Treuter, E. Mol. Endocrinol. (2002) [Pubmed]
  17. Identification of a novel missense mutation that is as damaging to DAX-1 repressor function as a nonsense mutation. Brown, P., Scobie, G.A., Townsend, J., Bayne, R.A., Seckl, J.R., Saunders, P.T., Anderson, R.A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  18. WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells. Gurates, B., Sebastian, S., Yang, S., Zhou, J., Tamura, M., Fang, Z., Suzuki, T., Sasano, H., Bulun, S.E. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  19. Immunolocalization of nuclear transcription factors, DAX-1 and COUP-TF II, in the normal human ovary: correlation with adrenal 4 binding protein/steroidogenic factor-1 immunolocalization during the menstrual cycle. Sato, Y., Suzuki, T., Hidaka, K., Sato, H., Ito, K., Ito, S., Sasano, H. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  20. Identification of a putative steroidogenic factor-1 response element in the DAX-1 promoter. Burris, T.P., Guo, W., Le, T., McCabe, E.R. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  21. Novel role for the orphan nuclear receptor Dax1 in embryogenesis, different from steroidogenesis. Niakan, K.K., Davis, E.C., Clipsham, R.C., Jiang, M., Dehart, D.B., Sulik, K.K., McCabe, E.R. Mol. Genet. Metab. (2006) [Pubmed]
  22. Orphan nuclear receptor DAX-1 in human endometrium and its disorders. Saito, S., Ito, K., Suzuki, T., Utsunomiya, H., Akahira, J., Sugihashi, Y., Niikura, H., Okamura, K., Yaegashi, N., Sasano, H. Cancer Sci. (2005) [Pubmed]
  23. Expression of sex-determining genes in human sebaceous glands and their possible role in the pathogenesis of acne. Chen, W., Yang, C.C., Liao, C.Y., Hung, C.L., Tsai, S.J., Chen, K.F., Sheu, H.M., Zouboulis, C.C. Journal of the European Academy of Dermatology and Venereology : JEADV. (2006) [Pubmed]
  24. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T.M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A.P., McCabe, E.R. Nature (1994) [Pubmed]
  25. Protein kinase A potentiates adrenal 4 binding protein/steroidogenic factor 1 transactivation by reintegrating the subcellular dynamic interactions of the nuclear receptor with its cofactors, general control nonderepressed-5/transformation/transcription domain-associated protein, and suppressor, dosage-sensitive sex reversal-1: a laser confocal imaging study in living KGN cells. Fan, W., Yanase, T., Wu, Y., Kawate, H., Saitoh, M., Oba, K., Nomura, M., Okabe, T., Goto, K., Yanagisawa, J., Kato, S., Takayanagi, R., Nawata, H. Mol. Endocrinol. (2004) [Pubmed]
  26. Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenita. Altincicek, B., Tenbaum, S.P., Dressel, U., Thormeyer, D., Renkawitz, R., Baniahmad, A. J. Biol. Chem. (2000) [Pubmed]
  27. DAX-1 functions as an LXXLL-containing corepressor for activated estrogen receptors. Zhang, H., Thomsen, J.S., Johansson, L., Gustafsson, J.A., Treuter, E. J. Biol. Chem. (2000) [Pubmed]
  28. DAX-1 gene mutations and deletions in Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Kinoshita, E., Yoshimoto, M., Motomura, K., Kawaguchi, T., Mori, R., Baba, T., Nishijo, K., Hasegawa, T., Momoi, T., Yorihuji, T. Horm. Res. (1997) [Pubmed]
  29. The orphan nuclear receptor DAX1 is up-regulated by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors. Mendiola, M., Carrillo, J., García, E., Lalli, E., Hernández, T., de Alava, E., Tirode, F., Delattre, O., García-Miguel, P., López-Barea, F., Pestaña, A., Alonso, J. Int. J. Cancer (2006) [Pubmed]
  30. Congenital adrenal hypoplasia and male pseudohermaphroditism due to DAX1 mutation, SF1 mutation or neither: a patient report. AvRuskin, T.W., Krishnan, N., Juan, C.S. Journal of pediatric endocrinology & metabolism : JPEM. (2004) [Pubmed]
  31. Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis. Guo, W., Burris, T.P., McCabe, E.R. Biochem. Mol. Med. (1995) [Pubmed]
  32. DAX-1 expression in human breast cancer: comparison with estrogen receptors ER-alpha, ER-beta and androgen receptor status. Conde, I., Alfaro, J.M., Fraile, B., Ruíz, A., Paniagua, R., Arenas, M.I. Breast Cancer Res. (2004) [Pubmed]
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