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Nuclear receptor subfamily 0, group B, member 1

Crystallographic structure of DAX-1 (rainbow colored, N-terminus = blue, C-terminus = red) complexed with LRH-1 (green).[1]
Available structures
External IDs OMIM300473 MGI1352460 HomoloGene403 GeneCards: NR0B1 Gene
RNA expression pattern
PBB GE NR0B1 206644 at tn.png
PBB GE NR0B1 206645 s at tn.png
More reference expression data
Species Human Mouse
Entrez 190 11614
Ensembl ENSG00000169297 ENSMUSG00000025056
UniProt P51843 Q53ZY9
RefSeq (mRNA) NM_000475 NM_007430
RefSeq (protein) NP_000466 NP_031456
Location (UCSC) Chr X:
30.23 - 30.24 Mb
Chr X:
82.44 - 82.45 Mb
PubMed search [1] [2]

DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) is a nuclear receptor protein encoded by the NR0B1 gene (nuclear receptor subfamily 0, group B, member 1).[2][3][4] The NR0B1 gene is located on the short (p) arm of the X chromosome between positions 21.3 and 21.2, from base pair 30,082,120 to base pair 30,087,136.



This gene encodes a protein that lacks the normal DNA-binding domain contained in other nuclear receptors.[5] The encoded protein acts as a dominant-negative regulator of transcription of other nuclear receptors including steroidogenic factor 1.[6] This protein also functions as an anti-testis gene by acting antagonistically to SRY. Mutations in this gene result in both X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism.[2]

DAX1 plays an important role in the normal development of several hormone-producing tissues. These tissues include the adrenal glands), the pituitary gland and hypothalamus which are located in the brain and the male and female reproductive structures (the testes and ovaries). DAX1 controls the activity of certain genes in the cells that form these tissues during embryonic development. Proteins that control the activity of other genes are known as transcription factors. DAX1 also plays a role in regulating hormone production in these tissues after they have been formed.

Role in disease

X-linked adrenal hypoplasia congenita is caused by mutations in the NR0B1 gene. More than 90 NR0B1 mutations that cause X-linked adrenal hypoplasia congenita have been identified. Many of these mutations delete all or part of the NR0B1 gene, preventing the production of DAX1 protein. Some mutations cause the production of an abnormally short protein. Other mutations cause a change in one of the building blocks (amino acids) of DAX1. These mutations are thought to result in a misshapen, nonfunctional protein. Loss of DAX1 function leads to adrenal insufficiency and hypogonadotropic hypogonadism, which are the main characteristics of this disorder.

Duplication of genetic material on the X chromosome in the region that contains the NR0B1 gene can cause a condition called dosage-sensitive sex reversal. The extra copy of the NR0B1 gene prevents the formation of male reproductive tissues. People who have this duplication usually appear to be female, but are genetically male with both an X and a Y chromosome.

In some cases, genetic material is deleted from the X chromosome in a region that contains several genes, including NR0B1. This deletion results in a condition called adrenal hypoplasia congenita with complex glycerol kinase deficiency. In addition to the signs and symptoms of adrenal hypoplasia congenita, individuals with this condition may have elevated levels of lipids in their blood and urine and may have problems regulating blood sugar levels. In rare cases, the amount of genetic material deleted is even more extensive and affected individuals also have Duchenne muscular dystrophy.


DAX1 has been shown to interact with COPS2,[7] Steroidogenic factor 1,[8][9] SREBF1[8] and NRIP1.[9]


  1. ^ PDB 3F5C: Sablin EP, Woods A, Krylova IN, Hwang P, Ingraham HA, Fletterick RJ (November 2008). "The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1". Proc. Natl. Acad. Sci. U.S.A. 105 (47): 18390–5. doi:10.1073/pnas.0808936105. PMID 19015525.  
  2. ^ a b "Entrez Gene: NR0B1 nuclear receptor subfamily 0, group B, member 1".  
  3. ^ Walker AP, Chelly J, Love DR, Brush YI, Récan D, Chaussain JL, Oley CA, Connor JM, Yates J, Price DA (November 1992). "A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes". Hum. Mol. Genet. 1 (8): 579–85. doi:10.1093/hmg/1.8.579. PMID 1301166.  
  4. ^ Goodfellow PN, Camerino G (June 1999). "DAX-1, an 'antitestis' gene". Cell. Mol. Life Sci. 55 (6-7): 857–63. doi:10.1007/PL00013201. PMID 10412368.  
  5. ^ McCabe ER (February 2007). "DAX1: Increasing complexity in the roles of this novel nuclear receptor". Mol. Cell. Endocrinol. 265-266: 179–82. doi:10.1016/j.mce.2006.12.017. PMID 17210221.  
  6. ^ Iyer AK, McCabe ER (2004). "Molecular mechanisms of DAX1 action". Mol. Genet. Metab. 83 (1-2): 60–73. doi:10.1016/j.ymgme.2004.07.018. PMID 15464421.  
  7. ^ Altincicek, B; Tenbaum S P, Dressel U, Thormeyer D, Renkawitz R, Baniahmad A (Mar. 2000). "Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenita". J. Biol. Chem. (UNITED STATES) 275 (11): 7662–7. ISSN 0021-9258. PMID 10713076.  
  8. ^ a b Lopez, D; Shea-Eaton W, Sanchez M D, McLean M P (Dec. 2001). "DAX-1 represses the high-density lipoprotein receptor through interaction with positive regulators sterol regulatory element-binding protein-1a and steroidogenic factor-1". Endocrinology (United States) 142 (12): 5097–106. ISSN 0013-7227. PMID 11713202.  
  9. ^ a b Sugawara, T; Abe S, Sakuragi N, Fujimoto Y, Nomura E, Fujieda K, Saito M, Fujimoto S (Aug. 2001). "RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1". Endocrinology (United States) 142 (8): 3570–7. ISSN 0013-7227. PMID 11459805.  

Further reading

  • Goodfellow PN, Camerino G (1999). "DAX-1, an 'antitestis' gene.". Cell. Mol. Life Sci. 55 (6-7): 857–63. doi:10.1007/PL00013201. PMID 10412368.  
  • Achermann JC, Meeks JJ, Jameson JL (2003). "Phenotypic spectrum of mutations in DAX-1 and SF-1.". Mol. Cell. Endocrinol. 185 (1-2): 17–25. doi:10.1016/S0303-7207(01)00619-0. PMID 11738790.  
  • Franzese A, Brunetti-Pierri N, Spagnuolo MI, et al. (2005). "Inappropriate tall stature and renal ectopy in a male patient with X-linked congenital adrenal hypoplasia due to a novel missense mutation in the DAX-1 gene.". Am. J. Med. Genet. A 135 (1): 72–4. doi:10.1002/ajmg.a.30670. PMID 15800903.  
  • Achermann JC (2005). "The role of SF1/DAX1 in adrenal and reproductive function.". Ann. Endocrinol. (Paris) 66 (3): 233–9. PMID 15988384.  
  • Niakan KK, McCabe ER (2006). "DAX1 origin, function, and novel role.". Mol. Genet. Metab. 86 (1-2): 70–83. doi:10.1016/j.ymgme.2005.07.019. PMID 16146703.  
  • Walker AP, Chelly J, Love DR, et al. (1993). "A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes.". Hum. Mol. Genet. 1 (8): 579–85. doi:10.1093/hmg/1.8.579. PMID 1301166.  
  • Worley KC, Towbin JA, Zhu XM, et al. (1992). "Identification of new markers in Xp21 between DXS28 (C7) and DMD.". Genomics 13 (4): 957–61. doi:10.1016/0888-7543(92)90007-F. PMID 1505987.  
  • Petersen KE, Bille T, Jacobsen BB, Iversen T (1983). "X-linked congenital adrenal hypoplasia. A study of five generations of a Greenlandic Family.". Acta paediatrica Scandinavica 71 (6): 947–51. doi:10.1111/j.1651-2227.1982.tb09554.x. PMID 6891556.  
  • Burris TP, Guo W, Le T, McCabe ER (1995). "Identification of a putative steroidogenic factor-1 response element in the DAX-1 promoter.". Biochem. Biophys. Res. Commun. 214 (2): 576–81. doi:10.1006/bbrc.1995.2324. PMID 7677767.  
  • Bardoni B, Zanaria E, Guioli S, et al. (1994). "A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal.". Nat. Genet. 7 (4): 497–501. doi:10.1038/ng0894-497. PMID 7951319.  
  • Zanaria E, Muscatelli F, Bardoni B, et al. (1995). "An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.". Nature 372 (6507): 635–41. doi:10.1038/372635a0. PMID 7990953.  
  • Muscatelli F, Strom TM, Walker AP, et al. (1995). "Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.". Nature 372 (6507): 672–6. doi:10.1038/372672a0. PMID 7990958.  
  • Guo W, Burris TP, McCabe ER (1996). "Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis.". Biochem. Mol. Med. 56 (1): 8–13. doi:10.1006/bmme.1995.1049. PMID 8593542.  
  • Yanase T, Takayanagi R, Oba K, et al. (1996). "New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism.". J. Clin. Endocrinol. Metab. 81 (2): 530–5. doi:10.1210/jc.81.2.530. PMID 8636263.  
  • Guo W, Burris TP, Zhang YH, et al. (1996). "Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.". J. Clin. Endocrinol. Metab. 81 (7): 2481–6. doi:10.1210/jc.81.7.2481. PMID 8675564.  
  • Nakae J, Tajima T, Kusuda S, et al. (1996). "Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.". J. Clin. Endocrinol. Metab. 81 (10): 3680–5. doi:10.1210/jc.81.10.3680. PMID 8855822.  
  • Schwartz M, Blichfeldt S, Müller J (1997). "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 (1): 83–7. doi:10.1007/s004390050316. PMID 9003500.  
  • Takahashi T, Shoji Y, Shoji Y, et al. (1997). "Active hypothalamic-pituitary-gonadal axis in an infant with X-linked adrenal hypoplasia congenita.". J. Pediatr. 130 (3): 485–8. doi:10.1016/S0022-3476(97)70217-8. PMID 9063431.  
  • Nakae J, Abe S, Tajima T, et al. (1997). "Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.". J. Clin. Endocrinol. Metab. 82 (11): 3835–41. doi:10.1210/jc.82.11.3835. PMID 9360549.  
  • Zazopoulos E, Lalli E, Stocco DM, Sassone-Corsi P (1997). "DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis.". Nature 390 (6657): 311–5. doi:10.1038/36899. PMID 9384387.  

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