protein
Spastin
Gene
SPAST
Organism
Homo sapiens(9606)
Length
616 aa
Mass
67,197 Da
Spastin (SPAST) is an ATP-dependent microtubule-severing protein that recognizes and cleaves polyglutamylated microtubules, with activity modulated by the length of glutamate tails on tubulin (UniProt: Q9UBP0). This severing activity is essential for reorganizing microtubule arrays and releasing microtubules from the centrosome, processes critical for axon biogenesis, spindle formation, and ciliary function. Spastin also participates in cytokinesis, nuclear envelope reassembly, endosomal trafficking, and lipid droplet regulation.
Mutations in SPAST cause spastic paraplegia 4 (SPG4), a neurodegenerative disorder characterized by progressive weakness and spasticity of the lower limbs, with variable severity and disease progression (UniProt: Q9UBP0). The protein functions in multiple cellular contexts including membrane trafficking, endosomal recycling, and cell division, reflecting its broad role in cytoskeletal dynamics.
Spastin is classified as SFARI Category 2 and associated with syndromic autism (SFARI Cat 2; SFARI Cat syndromic), indicating its relevance to autism spectrum disorder in the context of syndromic presentations linked to SPG4 and related neurodevelopmental complications.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Severing activity is not dependent on tubulin acetylation or detyrosination (PubMed:26875866). Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (PubMed:21310966). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (PubMed:23897888). Probably plays a role in axon growth and the formation of axonal branches (PubMed:15716377)
Involved in lipid metabolism by regulating the size and distribution of lipid droplets
Disease associations
Spastic paraplegia 4, autosomal dominantSPG4
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Sources
Last updated 5/6/2026, 5:23:49 AM