Species Human Entrez 6662 | Human Mouse Ensembl ENSG00000125398 | |
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Aliases SOX9, CMD1, CMPD1, SRA1, SRXX2, SRXY10, SRY-box 9 External IDs MGI: 98371 HomoloGene: 294 GeneCards: SOX9 | ||
Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.
Contents
Function
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.
SOX-9 also plays a pivotal role in male sexual development; by working with Sf1, SOX-9 can produce AMH in 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 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. Next, Sox9 activates FGF9 and forms feedforward loops with FGF9 and 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 testis cords and the multiplication of Sertoli cells. The association of SOX-9 and Dax1 actually creates Sertoli cells, another vital process in male development.
Clinical significance
Mutations lead to the skeletal malformation syndrome campomelic dysplasia, frequently with autosomal sex-reversal and 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 cleft palate.
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; the same is true if 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 Steroidogenic factor 1, MED12 and MAF.