This gene was identified as an ASD candidate gene following the identification of a balanced chromosomal abnormality (BCA) leading to gene disruption in an ASD case (Talkowski et al., 2012). This BCA-disrupted gene was also individually implicated by case-control CNV burden or by a minimum of 3 CNVs in neuodevelopmental disorder (NDD) cases with none in controls in a follow-up study in the same report. This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.
Molecular Function
ATP-dependent microtubule severing protein. Microtubule severing may promote reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and for completion of the abscission stage of cytokinesis. May also play a role in axon growth and the formation of axonal branches. Defects in SPAST are the cause of spastic paraplegia autosomal dominant type 4 (SPG4).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exons 5-7 of Spast gene are deleted using a targeting vector, with loxP and a neomycin cassette, inserted in between introns 4 and 7, followed by germline transmission of the floxed allele. Heterozygous flox/+ mice were crossed to CMV-cre mice to get germline knockout of exons 5-7.
Allele Type: Targeted (knockout)
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: PMID:17101632
Description: Increased number of abnormal axonal swellings containing organelles like mitochondria and lysosomes and filaments, spread throughout the axons, are seen in the spinal cord, specifically in the cervical and lumbar regions. these are observed to increase in number with age, no swellings are observable in wild type controls
Exp Paradigm: NA
Description: Truncated transcripts lacking exons 5-7 or alternatively spliced transcripts, with exon 4 spliced together with 8 were detected but no wild type protein was detected, tested in the brain or spinal cord
Exp Paradigm: NA
