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Title: Sox9  
Author: World Heritage Encyclopedia
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Subject: Steroidogenic factor 1, PAX7, MAF (gene), Sex-determination system, Defeminization and masculinization
Publisher: World Heritage Encyclopedia


SRY (sex determining region Y)-box 9

Rendering based on PDB .
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; CMD1; CMPD1; SRA1
External IDs GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.[1][2]


SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It acts during chondrocyte differentiation and, with steroidogenic factor 1, regulates transcription of the anti-Müllerian hormone (AMH) gene.[2]

SOX-9 also plays a pivotal role in male sexual development; by working with Sf1, SOX-9 can produce AMH in Testis determining factor (encoded by the sex-determining region SRY of the Y chromosome) activates SOX-9 activity by binding to an enhancer sequence upstream of the gene.[4] Next, Sox9 activates FGF9 and forms feedforward loops with FGF9[5] and PGD2.[4] These loops are important for producing SOX-9; without these loops, SOX-9 would run out and the development of a female would almost certainly ensue. Activation of FGF9 by SOX-9 starts vital processes in male development, such as the creation of testis cords and the multiplication of Sertoli cells.[5] The association of SOX-9 and Dax1 actually creates Sertoli cells, another vital process in male development.[6]

Clinical significance

Mutations lead to the skeletal malformation syndrome campomelic dysplasia, frequently with autosomal sex-reversal[2] and cleft palate.[7]

SOX9 sits in a gene desert on 17q24 in humans. Deletions, disruptions by translocation breakpoints and a single point mutation of highly conserved non-coding elements located > 1 Mb from the transcription unit on either side of SOX9 have been associated with Pierre Robin Sequence, often with a cleft palate.[8][7]

Role in sex reversal

Mutations in Sox9 or any associated genes can cause reversal of sex or even hermaphroditism. If Fgf9, which is activated by Sox9, is not present, a fetus with both X and Y chromosomes can be converted into a female;[4] the same is true if Dax1 is not present.[6] The related problem of hermaphroditism can be caused by unusual activity of the SRY, usually when it's translocated onto the X-chromosome and its activity is only activated in some cells.[9]


SOX9 has been shown to interact with Steroidogenic factor 1,[3] MED12[10] and MAF.[11]

See also


  1. ^ Tommerup N, Schempp W, Meinecke P, Pedersen S, Bolund L, Brandt C, Goodpasture C, Guldberg P, Held KR, Reinwein H, et al. (Sep 1993). "Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1". Nat Genet 4 (2): 170–4.  
  2. ^ a b c "Entrez Gene: SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal)". 
  3. ^ a b De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P (November 1998). "Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene". Mol. Cell. Biol. 18 (11): 6653–65.  
  4. ^ a b c Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, Marzi L, Cohen-Solal A, Georg I, Klattig J, Englert C, Kim Y, Capel B, Eguchi N, Urade Y, Boizet-Bonhoure B, Poulat F (June 2009). "The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation". Development 136 (11): 1813–21.  
  5. ^ a b Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R, Capel B (June 2006). "Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination". PLoS Biol. 4 (6): e187.  
  6. ^ a b Bouma GJ, Albrecht KH, Washburn LL, Recknagel AK, Churchill GA, Eicher EM (July 2005). "Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells". Development 132 (13): 3045–54.  
  7. ^ a b Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nat. Rev. Genet. 12 (3): 167–78.  
  8. ^ Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, Jamshidi N, Essafi A, Heaney S, Gordon CT, McBride D, Golzio C, Fisher M, Perry P, Abadie V, Ayuso C, Holder-Espinasse M, Kilpatrick N, Lees MM, Picard A, Temple IK, Thomas P, Vazquez MP, Vekemans M, Roest Crollius H, Hastie ND, Munnich A, Etchevers HC, Pelet A, Farlie PG, Fitzpatrick DR, Lyonnet S (March 2009). "Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence". Nat. Genet. 41 (3): 359–64.  
  9. ^ Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F (January 2000). "SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite". Am. J. Med. Genet. 90 (1): 25–8.  
  10. ^ Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S (July 2002). "SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex". Nucleic Acids Res. 30 (14): 3245–52.  
  11. ^ Huang W, Lu N, Eberspaecher H, De Crombrugghe B (December 2002). "A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene". J. Biol. Chem. 277 (52): 50668–75.  

Further reading

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