The SPAST gene provides instructions for producing a protein called spastin, which is a member of the AAA protein family. This protein family plays a role in many cellular activities, including regulation of cell components and proteins. Spastin is found throughout the body, particularly in certain nerve cells (neurons). The spastin protein plays a role in the function of microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules are also involved in transporting cell compartments (organelles) and facilitating cell division. Spastin likely helps regulate microtubule length and disassemble microtubule structures when they are no longer needed.
Several hundred mutations in the SPAST gene have been found to cause spastic paraplegia type 4. This condition is characterized by muscle weakness, progressive muscle stiffness (spasticity) in the legs, and difficulty walking. Most of these mutations alter the structure or disrupt the production of spastin, impairing its ability to regulate microtubules. The inability of the microtubules to transport organelles, especially in nerve cells, is thought to contribute to the major signs and symptoms of spastic paraplegia type 4.
Mutation in the SPAST gene account for approximately 40 percent of autosomal dominant hereditary spastic paraplegias.
- spastic paraplegia 4 (autosomal dominant; spastin)