CHSY1

This protein functions as a dual transferase enzyme that synthesizes chondroitin sulfate by adding both glucuronic acid and N-acetylgalactosamine to the growing polymer chain, and negatively regulates bone formation through modulation of NOTCH signaling. Mutations cause Temtamy preaxial brachydactyly syndrome, which involves limb malformations, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.405), indicating that such mutations are typically not tolerated.