Current knowledge of the complex modular organization of SOX9 cis-acting elements. The domain topologically associated with SOX9 spans 1.9 Mb upstream and 0.5 Mb downstream of the gene. The SOX9 proximal region is believed to be a hub for signaling pathways. The distal regions house at least a dozen and likely more enhancers driving gene expression in various tissues, chondrocyte differentiation stages, and cartilage anatomical sites. The upstream region also houses ROCR,
SOX9-regulating IncRNAs. Chromosomal translocations, microdeletions and duplications in the distal regions cause chondrodysplasias (CMPD, ACMPD, and PRS) and disorders of sex development (DSD) with a severity generally proportional to their proximity to the SOX9 gene body.