CHST3

The CHST3 gene provides instructions for making an enzyme called chondroitin 6-O-sulfotransferase 1 or C6ST-1. This enzyme has an important role in the development and maintenance of the skeleton. In particular, it is essential for the normal development of cartilage, which is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.

The C6ST-1 enzyme modifies molecules called chondroitin sulfate proteoglycans, which are abundant in cartilage and give this tissue its rubbery, gel-like consistency. The C6ST-1 enzyme carries out a process known as sulfation, in which a sulfur-containing molecule called a sulfate is transferred from one chemical compound to another. Specifically, the enzyme takes sulfate from a molecule called 3'-phosphoadenyl-5'-phosphosulfate (PAPS) and adds it to a specific location on chondroitin sulfate proteoglycans. Sulfation of these molecules is a critical step in cartilage formation.

CHST3-related skeletal dysplasia - caused by mutations in the CHST3 gene

At least 24 mutations in the CHST3 gene have been found to cause CHST3-related skeletal dysplasia, a condition characterized by progressive bone and joint abnormalities. Most of the mutations change single protein building blocks (amino acids) in the C6ST-1 enzyme. Other mutations result in the production of an abnormally short version of the enzyme. Each of these genetic changes reduces or eliminates the activity of C6ST-1, preventing it from transferring sulfate groups to chondroitin sulfate proteoglycans. Defective sulfation of these molecules disrupts the normal development of cartilage and bone, resulting in short stature, joint dislocations, and the other features of CHST3-related skeletal dysplasia.