SOST gene
The SOST gene provides instructions for producing the protein sclerostin, which acts as a negative regulator of bone formation to maintain healthy bone density and structure.
Normal Function
The SOST gene provides instructions for making the protein sclerostin. Sclerostin is produced in bone cells called osteocytes and plays an important role in bone formation.
Bone remodeling is a normal process in which old bone is broken down and new bone is formed. Bone remodeling is carefully controlled to ensure that bones stay strong and healthy. It requires a balance between the formation of new bone tissue and the breakdown and removal (resorption) of old bone tissue. The main function of sclerostin is to stop (inhibit) bone formation. Inhibiting bone formation helps to ensure that bones are the correct shape, size, and density.
Research suggests that sclerostin works by interfering with a process called Wnt signaling, which plays a key role in the regulation of bone formation. Sclerostin may also promote the self-destruction (apoptosis) of bone cells, further inhibiting bone growth.
Health Conditions Related to Genetic Changes
SOST-related sclerosing bone dysplasia
Genetic changes in or near the SOST gene can cause SOST-related sclerosing bone dysplasias, which are characterized by abnormal hardening (sclerosis) of the bone and increased bone formation (hyperostosis). As a result of hyperostosis, bones throughout the body may be wider and denser than normal, particularly the bones of the skull, lower jaw (mandible), arms, and legs. There are two forms of SOST-related sclerosing bone dysplasia: SOST-related sclerosteosis and van Buchem disease (also called SOST-related endosteal hyperostosis, van Buchem type). Although the features seen in people with van Buchem disease may overlap with those seen in people with SOST-related sclerosteosis, they tend to be less severe.
The changes in the SOST gene that cause SOST-related sclerosteosis are known as “loss-of-function variants” because they reduce the activity of sclerostin or decrease the amount of sclerostin that is produced by the cells. Some of the variants prevent the production of any functional sclerostin. This disrupts the ability to inhibit bone growth and causes the hyperostosis seen in affected individuals.
Changes in a region of DNA near the SOST gene cause van Buchem disease. The most common change in people with van Buchem disease is the deletion of a region of DNA that helps regulate the activity (expression) of the SOST gene. This decreases SOST gene expression and reduces protein production, which leads to a shortage of functional sclerostin protein. A shortage of sclerostin disrupts the protein's ability to inhibit bone growth, allowing the hyperostosis seen in people with van Buchem disease.
Other disorders
Genetic changes in the SOST gene have also been found to cause SOST-related craniodiaphyseal dysplasia, an extremely rare condition that causes hyperostosis. However, people with SOST-related craniodiaphyseal dysplasia typically have more severe hyperostosis of the bones in the skull than people with SOST-related sclerosing bone dysplasias. In people with SOST-related craniodiaphyseal dysplasia, hyperostosis of the bones in the skull compress the nerves of the head and neck and increase the pressure on parts of the brain. Affected individuals may also have a narrowing of the nasal passages (choanal atresia), which can cause breathing problems. Because the signs and symptoms seen in people with SOST-related craniodiaphyseal dysplasia tend to be severe, affected individuals often do not survive past childhood. The changes in the SOST gene that are associated with craniodiaphyseal dysplasia cause cells to make a version of sclerostin that cannot inhibit bone growth, allowing excessive bone formation.
Other Names for This Gene
- DAND6
- sclerosteosis
- sclerostin precursor
- VBCH