Associated disorders

The SPAST gene is associated with autosomal dominant hereditary spastic paraplegia 4 (SPG4) (MedGen UID: 401097).

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An estimated 22%-45% of autosomal dominant HSP is caused by pathogenic variants in SPAST.

The SPAST gene encodes the spastin protein, which cleaves microtubules, playing a role in cytoskeletal dynamics and the transport of organelles on microtubules.

  1. Depienne, C, et al. Hereditary spastic paraplegias: an update. Curr. Opin. Neurol. 2007; 20(6):674-80. doi: 10.1097/WCO.0b013e3282f190ba. PMID: 17992088
  2. Fink, JK. Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. Acta Neuropathol. 2013; 126(3):307-28. doi: 10.1007/s00401-013-1115-8. PMID: 16469273
  3. Errico, A, et al. Spastin interacts with the centrosomal protein NA14, and is enriched in the spindle pole, the midbody and the distal axon. Hum. Mol. Genet. 2004; 13(18):2121-32. doi: 10.1093/hmg/ddh223. PMID: 15269182
  4. Svenson, IK, et al. Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. Am. J. Hum. Genet. 2001; 68(5):1077-85. doi: 10.1086/320111. PMID: 11309678
  5. Dürr, A, et al. Spastic Paraplegia 4. 2003 Apr 17. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301339
  6. Errico, A, et al. Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. Hum. Mol. Genet. 2002; 11(2):153-63. doi: 10.1093/hmg/11.2.153. PMID: 11809724
  7. Crippa, F, et al. Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia. Arch. Neurol. 2006; 63(5):750-5. doi: 10.1001/archneur.63.5.750. PMID: 16682546
  8. McDermott, CJ, et al. Hereditary spastic paraparesis: disrupted intracellular transport associated with spastin mutation. Ann. Neurol. 2003; 54(6):748-59. doi: 10.1002/ana.10757. PMID: 14681884

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
SPAST NM_014946.3