Meyahealth
HomeGeneticsGeneSPAST gene
Back to Gene
SPAST gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SPAST gene

The SPAST gene encodes the microtubule‑severing protein spastin, and mutations in this gene are a major cause of autosomal dominant hereditary spastic paraplegia type 4.

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.

Other 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

  • Tests of SPAST

Scientific Articles on PubMed

  • PubMed

Catalog of Genes and Diseases from OMIM

  • SPASTIN; SPAST

Gene and Variant Databases

  • NCBI Gene
  • ClinVar

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. Citation on PubMed or Free article on PubMed Central

Genomic Location

The SPAST gene is found on chromosome 2.

MEDICAL ENCYCLOPEDIA

  • Genes
  • Genetics

Understanding Genetics

  • What is DNA?
  • What is a gene?
  • What is a gene variant and how do variants occur?

MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. MedlinePlus also links to health information from non-government Web sites. See our disclaimer about external links and our quality guidelines.

Frequently Asked Questions

Spastic paraplegia type 4 (HSP4) primarily causes progressive muscle weakness and stiffness (spasticity) in the legs, leading to increasing difficulty with walking. These symptoms typically worsen over time and can affect balance and coordination.
The spastin protein, encoded by the SPAST gene, helps regulate the length and disassembly of microtubules, which are vital for transporting materials within nerve cells (neurons). When spastin is dysfunctional due to a mutation, microtubules cannot function properly, impairing the transport of essential components within neurons, especially in the long nerves of the spinal cord, leading to the characteristic muscle weakness and spasticity in the legs.
HSP4 caused by SPAST gene mutations is inherited in an autosomal dominant pattern. This means that only one copy of the altered gene in each cell is sufficient to cause the disorder. A person with HSP4 has a 50% chance of passing the condition on to each of their children.
While there is currently no cure for spastic paraplegia type 4, treatment focuses on managing symptoms and improving quality of life. This often includes physical therapy, occupational therapy, and medications to reduce muscle spasticity. Assistive devices like braces or walkers may also be used to help with mobility.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ