SOX9

Transcription factor SOX-9 is a is_associated_with::protein that in humans is encoded by the SOX9 is_associated_with::gene.

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

SOX-9 also plays a pivotal role in male sexual development; by working with Sf1, SOX-9 can produce AMH in is_associated_with::Sertoli cells to inhibit the creation of a female reproductive system. It also interacts with a few other genes to promote the development of male sexual organs. The process starts when the transcription factor is_associated_with::Testis determining factor (encoded by the sex-determining region is_associated_with::SRY of the is_associated_with::Y chromosome) activates SOX-9 activity by binding to an enhancer sequence upstream of the gene. Next, Sox9 activates is_associated_with::FGF9 and forms feedforward loops with FGF9 and is_associated_with::PGD2. 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 is_associated_with::testis cords and the multiplication of is_associated_with::Sertoli cells. The association of SOX-9 and is_associated_with::Dax1 actually creates Sertoli cells, another vital process in male development.

Clinical significance
Mutations lead to the skeletal malformation syndrome is_associated_with::campomelic dysplasia, frequently with autosomal sex-reversal and is_associated_with::cleft palate.

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 is_associated_with::cleft palate.

Role in sex reversal
is_associated_with::Mutations in Sox9 or any associated genes can cause reversal of sex or even is_associated_with::hermaphroditism. If Fgf9, which is activated by Sox9, is not present, a is_associated_with::fetus with both X and Y is_associated_with::chromosomes can be converted into a female; the same is true if is_associated_with::Dax1 is not present. 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.

Interactions
SOX9 has been shown to interact with is_associated_with::Steroidogenic factor 1, is_associated_with::MED12 and MAF.