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Normal Function
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.
Health Conditions Related to Genetic Changes
Spastic paraplegia type 4
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.
More About This Health ConditionOther Names for This Gene
- ADPSP
- FSP2
- KIAA1083
- SPAST_HUMAN
- spastic paraplegia 4 (autosomal dominant; spastin)
- SPG4
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Blackstone C. Hereditary spastic paraplegia. Handb Clin Neurol. 2018;148:633-652. doi: 10.1016/B978-0-444-64076-5.00041-7. Citation on PubMed
- Claudiani P, Riano E, Errico A, Andolfi G, Rugarli EI. Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. Exp Cell Res. 2005 Oct 1;309(2):358-69. doi: 10.1016/j.yexcr.2005.06.009. Citation on PubMed
- Kuo YW, Trottier O, Mahamdeh M, Howard J. Spastin is a dual-function enzyme that severs microtubules and promotes their regrowth to increase the number and mass of microtubules. Proc Natl Acad Sci U S A. 2019 Mar 19;116(12):5533-5541. doi: 10.1073/pnas.1818824116. Epub 2019 Mar 5. Citation on PubMed or Free article on PubMed Central
- McNally FJ, Roll-Mecak A. Microtubule-severing enzymes: From cellular functions to molecular mechanism. J Cell Biol. 2018 Dec 3;217(12):4057-4069. doi: 10.1083/jcb.201612104. Epub 2018 Oct 29. Citation on PubMed or Free article on PubMed Central
- Roll-Mecak A, Vale RD. Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin. Nature. 2008 Jan 17;451(7176):363-7. doi: 10.1038/nature06482. Citation on PubMed or Free article on PubMed Central
- Sandate CR, Szyk A, Zehr EA, Lander GC, Roll-Mecak A. An allosteric network in spastin couples multiple activities required for microtubule severing. Nat Struct Mol Biol. 2019 Aug;26(8):671-678. doi: 10.1038/s41594-019-0257-3. Epub 2019 Jul 8. Erratum In: Nat Struct Mol Biol. 2020 Apr;27(4):400. doi: 10.1038/s41594-020-0414-8. Citation on PubMed or Free article on PubMed Central
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