EXT2 gene
The EXT2 gene provides instructions for the exostosin-2 protein, which works with exostosin-1 to regulate heparan sulfate production and bone development.
Normal Function
The EXT2 gene provides instructions for producing a protein called exostosin-2. Like exostosin-1, this protein is found in the Golgi apparatus. It binds to exostosin-1 to form a complex that modifies heparan sulfate, a sugar-molecule complex essential for cell signaling, immune function, and the regulation of bone formation and cartilage development.
Health Conditions Related to Genetic Changes
Hereditary multiple osteochondromas
Pathogenic variants in the EXT2 gene cause hereditary multiple osteochondromas type 2. These "loss-of-function variants" prevent the production of functional exostosin-2. Without this protein, the complex with exostosin-1 cannot form, leading to improper heparan sulfate modification and the development of multiple benign bone tumors (osteochondromas).
Potocki-Shaffer syndrome
This condition is caused by a deletion of genetic material on chromosome 11. The loss of the EXT2 gene within this region results in multiple osteochondromas. Other features of the syndrome, such as enlarged parietal foramina (openings in the skull) and intellectual disabilities, are caused by the loss of additional genes in the same deleted region, such as ALX4 and PHF21A.
Other disorders
Pathogenic variants in the EXT2 gene have been linked to seizures-scoliosis-macrocephaly syndrome. In this condition, variants occur in both copies of the gene, leading to a reduction in functional exostosin-2. This disrupts heparan sulfate modification, resulting in symptoms including seizures, spinal curvature (scoliosis), an unusually large head (macrocephaly), intellectual disabilities, and low muscle tone (hypotonia).
Other Names for This Gene
- exostosin 2
- SOTV