Transcription factor that plays a key role in chondrocytes differentiation and skeletal development. Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes ...[+]

Transcription factor that plays a key role in chondrocytes differentiation and skeletal development. Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including COL2A1. Plays a central role in successive steps of chondrocyte differentiation. Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes. Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis. Later, required to direct hypertrophic maturation and block osteoblast differentiation of growth plate chondrocytes: maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation of chondrocytes. Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells. Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation. In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells. Unlikely to play a role in sex determination but may function during testicular and ovarian differentiation (PubMed:18692165, PubMed:18816826). [-]

             46,XY complete gonadal dysgenesis
             46,XY sex reversal 10

          46,XY SEX REVERSAL 10; SRXY10

ClinVar, ClinGen, MalaCards, KEGG Disease, DECIPHER, COSMIC, MARRVEL, GTR, DisGeNET, dbVAR, GHR, gnomAD