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Home > A. Molecular pathology > NR0B1


MIM.300473 Xp21.3-p21.2

Tuesday 28 June 2005

NR0B1 (DAX1) is an orphan member of the nuclear receptor (NRs) superfamily. It functions in the proper formation of the adult adrenal gland.

NR0B1 has a unique role as a member of NRs in that it acts as a coregulatory protein that inhibits the transcriptional activity of other NRs


- germline mutations of DAX1 in

  • dosage sensitive male-to-female sex reversal (MIM.300018)
  • delayed-onset adrenal insufficiency and hypogonadotrophic hypogonadism


- Ludbrook LM, Harley VR. Sex determination: a ’window’ of DAX1 activity. Trends Endocrinol Metab. 2004 Apr;15(3):116-21. PMID: 15046740


- Iyer, A. K.; Zhang, Y.-H.; McCabe, E. R. B. : LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1 (NR0B1)-DAX1A heterodimerization. Molec. Genet. Metab. 92: 151-159, 2007. PubMed ID : 17686645

- Iyer, A. K.; Zhang, Y.-H.; McCabe, E. R. B. : Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers. Molec. Endocr. 20: 2326-2342, 2006. PubMed ID : 16709599

- Lin, L.; Gu, W.-X.; Ozisik, G.; To, W. S.; Owen, C. J.; Jameson, J. L.; Achermann, J. C. : Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years’ experience. J. Clin. Endocr. Metab. 91: 3048-3054, 2006. PubMed ID : 16684822

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- Molecular mechanisms of DAX1 action. Iyer AK, McCabe ER. Mol Genet Metab. 2004 Sep-Oct;83(1-2):60-73. PMID: 15464421

- NR0B1A: an alternatively spliced form of NR0B1. Ho J, Zhang YH, Huang BL, McCabe ER. Mol Genet Metab. 2004 Dec;83(4):330-6. PMID: 15589120

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- Lehmann, S. G.; Wurtz, J.-M.; Renaud, J.-P.; Sassone-Corsi, P.; Lalli, E. : Structure-function analysis reveals the molecular determinants of the impaired biological function of DAX-1 mutants in AHC patients. Hum. Molec. Genet. 12: 1063-1072, 2003. PubMed ID : 12700175

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- McCabe, E. R. B. : Sex and the single DAX1: too little is bad, but can we have too much? (Editorial) J. Clin. Invest. 98: 881-882, 1996. PubMed ID : 8770856

- Meeks, J. J.; Weiss, J.; Jameson, J. L. : Dax1 is required for testis determination. Nature Genet. 34: 32-33, 2003. PubMed ID : 12679814

- Merke, D. P.; Tajima, T.; Baron, J.; Cutler, G. B., Jr. : Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene. New Eng. J. Med. 340: 1248-1252, 1999. PubMed ID : 10210708

- Muscatelli, F.; Strom, T. M.; Walker, A. P.; Zanaria, E.; Recan, D.; Meindl, A.; Bardoni, B.; Guioli, S.; Zehetner, G.; Rabl, W.; Schwarz, H. P.; Kaplan, J.-C.; Camerino, G.; Meitinger, T.; Monaco, A. P. : Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature 372: 672-676, 1994. PubMed ID : 7990958

- Nachtigal, M. W.; Hirokawa, Y.; Enyeart-VanHouten, D. L.; Flanagan, J. N.; Hammer, G. D.; Ingraham, H. A. : Wilms’ tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression. Cell 93: 445-454, 1998. PubMed ID : 9590178

- Nakae, J.; Abe, S.; Tajima, T.; Shinohara, N.; Murashita, M.; Igarashi, Y.; Kusuda, S.; Suzuki, J.; Fujieda, K. : Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita. J. Clin. Endocr. Metab. 82: 3835-3841, 1997.
PubMed ID : 9360549

- Nakae, J.; Tajima, T.; Kusuda, S.; Kohda, N.; Okabe, T.; Shinohara, N.; Kato, M.; Murashita, M.; Mukai, T.; Imanaka, K.; Fujieda, K. : Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita. J. Clin. Endocr. Metab. 81: 3680-3685, 1996. PubMed ID : 8855822

- Niakan, K. K.; McCabe, E. R. B. : DAX1 origin, function, and novel role. Molec. Genet. Metab. 86: 70-83, 2005. PubMed ID : 16146703

- Ozisik, G.; Mantovani, G.; Achermann, J. C.; Persani, L.; Spada, A.; Weiss, J.; Beck-Peccoz, P.; Jameson, J. L. : An alternate translation initiation site circumvents an amino-terminal DAX1 nonsense mutation leading to a mild form of X-linked adrenal hypoplasia congenita. J. Clin. Endocr. Metab. 88: 417-423, 2003. PubMed ID : 12519885

- Peter, M.; Viemann, M.; Partsch, C.-J.; Sippell, W. G. : Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene. J. Clin. Endocr. Metab. 83: 2666-2674, 1998. PubMed ID : 9709929

- Petersen, K. E.; Bille, T.; Jacobsen, B. B.; Iversen, T. :
X-linked congenital adrenal hypoplasia: a study of five generations of a Greenlandic family. Acta Paediat. Scand. 71: 947-951, 1982.
PubMed ID : 6891556

- Phelan, J. K.; McCabe, E. R. B. : Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita. Hum. Mutat. 18: 472-487, 2001. PubMed ID : 11748841

- Reincke, M.; Beuschlein, F.; Lalli, E.; Arlt, W.; Vay, S.; Sassone-Corsi, P.; Allolio, B. : DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis. J. Clin. Endocr. Metab. 83: 2597-2600, 1998. PubMed ID : 9661652

- Salvi, R.; Gomez, F.; Fiaux, M.; Schorderet, D.; Jameson, J. L.; Achermann, J. C.; Gaillard, R. C.; Pralong, F. P. : Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin caused by a complex genetic rearrangement within DAX-1. J. Clin. Endocr. Metab. 87: 4094-4100, 2002. PubMed ID : 12213854

- Schwartz, M.; Blichfeldt, S.; Muller, J. : X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis. Hum. Genet. 99: 83-87, 1997. PubMed ID : 9003500

- Seminara, S. B.; Achermann, J. C.; Genel, M.; Jameson, J. L.; Crowley, W. F., Jr. : X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females. J. Clin. Endocr. Metab. 84: 4501-4509, 1999. PubMed ID : 10599709

- Swain, A.; Narvaez, V.; Burgoyne, P.; Camerino, G.; Lovell-Badge, R. : Dax1 antagonizes Sry action in mammalian sex determination. Nature 391: 761-767, 1998. PubMed ID : 9486644

- Swain, A.; Zanaria, E.; Hacker, A.; Lovell-Badge, R.; Camerino, G. : Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function. Nature Genet. 12: 404-409, 1996. PubMed ID : 8630494

- Tabarin, A.; Achermann, J. C.; Recan, D.; Bex, V.; Bertagna, X.; Christin-Maitre, S.; Ito, M.; Jameson, J. L.; Bouchard, P. : A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism. J. Clin. Invest. 105: 321-328, 2000. PubMed ID : 10675358

- Takayanagi, R.; Okabe, T.; Sakai, O.; Nawata, H.; Kato, K.; Ibayashi, H. :
A case of congenital adrenal hypoplasia and hypogonadism. Horumon to Rinsho 40: 81-84, 1992.

- Tamai, K. T.; Monaco, L.; Alastalo, T.-P.; Lalli, E.; Parvinen, M.; Sassone-Corsi, P. : Hormonal and developmental regulation of DAX-1 expression in Sertoli cells. Molec. Endocr. 10: 1561-1569, 1996. PubMed ID : 8961266

- Telvi, L.; Ion, A.; Carel, J.-C.; Desguerre, I.; Piraud, M.; Boutin, A. M.; Feingold, J.; Ponsot, G.; Fellous, M.; McElreavey, K. : A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities. J. Med. Genet. 33: 767-771, 1996. PubMed ID : 8880579

- Verrijn Stuart, A. A.; Ozisik, G.; de Vroede, M. A.; Giltay, J. C.; Sinke, R. J.; Peterson, T. J.; Harris, R. M.; Weiss, J.; Jameson, J. L. : An amino-terminal DAX1 (NROB1) missense mutation associated with isolated mineralocorticoid deficiency. J. Clin. Endocr. Metab. 92: 755-761, 2007. PubMed ID : 17164309

- Wang, J.; Killinger, D. W.; Hegele, R. A. : A microdeletion within DAX-1 in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism. J. Invest. Med. 47: 232-235, 1999.

- Yanase, T.; Takayanagi, R.; Oba, K.; Nishi, Y.; Ohe, K.; Nawata, H. : New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism. J. Clin. Endocr. Metab. 81: 530-535, 1996. PubMed ID : 8636263

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- Zanaria, E.; Muscatelli, F.; Bardoni, B.; Strom, T. M.; Guioli, S.; Guo, W.; Lalli, E.; Moser, C.; Walker, A. P.; McCabe, E. R. B.; Meitinger, T.; Monaco, A. P.; Sassone-Corsi, P.; Camerino, G. : An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature 372: 635-641, 1994. PubMed ID : 7990953

- Zazopoulos, E.; Lalli, E.; Stocco, D. M.; Sassone-Corsi, P. : DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis. Nature 390: 311-315, 1997. PubMed ID : 9384387

- Zhang, Y.-H.; Guo, W.; Wagner, R. L.; Huang, B.-L.; McCabe, L.; Vilain, E.; Burris, T. P.; Anyane-Yeboa, K.; Burghes, A. H. M.; Chitayat, D.; Chudley, A. E.; Genel, M.; and 12 others : DAX1 mutations map to putative structural domains in a deduced three-dimensional model. Am. J. Hum. Genet. 62: 855-864, 1998. PubMed ID : 9529340