NR5A1
HGNC:7983 9q33 Entrez:2516 MIM.184757
Steroidogenic factor-1 (SF-1/Ad4-binding protein; NR5A1) is an essential regulator of tissue-specific gene expression in steroidogenic cells and of adrenogonadal development.
SF-1 binds as a monomer to nuclear receptor half sites on DNA. Its transcriptional activity can be regulated by putative phospholipid ligands that bind inside its hydrophobic pocket, and by post-translational modifications, namely phosphorylation by different kinases at Ser203 and sumoylation, which may affect subnuclear localization of SF-1 and its DNA-binding activity.
Pathology
XY sex reversal with adrenal failure (MIM.612965)
See also
complete or partial 46,XY gonadal dysgenesis
46,XY disorder of sexual development (46,XY DSD)
Reviews
Adrenocortical development and cancer: focus on SF-1. Lalli E. J Mol Endocrinol. 2010 Jun;44(6):301-7. PMID: #20200142#
References
Partial deletion of the NR5A1 (SF1) gene detected by synthetic probe MLPA in a patient with XY gonadal disorder of sex development. Barbaro M, Cools M, Looijenga LH, Drop SL, Wedell A. Sex Dev. 2011;5(4):181-7. PMID: #21654157#
Lourenco, D.; Brauner, R.; Lin, L.; De Perdigo, A.; Weryha, G.; Muresan, M.; Boudjenah, R.; Guerra-Junior, G.; Maciel-Guerra, A. T.; Achermann, J. C.; McElreavey, K.; Bashamboo, A. : Mutations in the NR5A1 associated with ovarian insufficiency. New Eng. J. Med. 360: 1200-1210, 2009. PubMed ID : #19246354#
Kohler, B.; Lin, L.; Ferraz-de-Souza, B.; Wieacker, P.; Heidemann, P.; Schroder, V.; Biebermann, H.; Schnabel, D.; Gruters, A.; Achermann, J. C. : Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum. Mutat. 29: 59-64, 2008. PubMed ID : #17694559#
Lin, L.; Philibert, P.; Ferraz-de-Souza, B.; Kelberman, D.; Homfray, T.; Albanese, A.; Molini, V.; Sebire, N. J.; Einaudi, S.; Conway, G. S.; Hughes, I. A.; Jameson, J. L.; Sultan, C.; Dattani, M. T.; Achermann, J. C. : Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function. J. Clin. Endocr. Metab. 92: 991-999, 2007. PubMed ID : #17200175#
Lee, P. A.; Houk, C. P.; Ahmed, S. F.; Hughes, I. A. : Consensus statement on management of intersex disorders. Pediatrics 118: e488-e500, 2006. Note: Electronic Article. PubMed ID : #16882788#
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#
Hasegawa, T.; Fukami, M.; Sato, N.; Katsumata, N.; Sasaki, G.; Fukutani, K.; Morohashi, K.-I.; Ogata, T. : Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1. J. Clin. Endocr. Metab. 89: 5930-5935, 2004. PubMed ID : #15579739#
Correa, R. V.; Domenice, S.; Bingham, N. C.; Billerbeck, A. E. C.; Rainey, W. E.; Parker, K. L.; Mendonca, B. B. : A microdeletion in the ligand binding domain of human steroidogenic factor 1 causes XY sex reversal without adrenal insufficiency. J. Clin. Endocr. Metab. 89: 1767-1772, 2004. PubMed ID : #15070943#
Achermann, J. C.; Ito, M.; Ito, M.; Hindmarsh, P. C.; Jameson, J. L. : A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. (Letter) Nature Genet. 22: 125-126, 1999. PubMed ID : #10369247#
Luo, X.; Ikeda, Y.; Parker, K. L. : A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77: 481-490, 1994. PubMed ID : #8187173#
Berkovitz, G. D.; Fechner, P. Y.; Zacur, H. W.; Rock, J. A.; Snyder, H. M, 3rd; Migeon C. J.; Perlman, E. J. : Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation. Medicine 70: 375-383, 1991. PubMed ID : #1956279#