SPASTSpastin
Autism Reports / Total Reports
12 / 17Rare Variants / Common Variants
16 / 0Aliases
SPAST, ADPSP, FSP2, KIAA1083, SPG4Associated Syndromes
-Chromosome Band
2p22.3Associated Disorders
-Genetic Category
Rare Single Gene Mutation, SyndromicRelevance to Autism
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
SFARI Genomic Platforms
Reports related to SPAST (17 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | Patterns and rates of exonic de novo mutations in autism spectrum disorders | Neale BM , et al. (2012) | Yes | - |
| 2 | Primary | Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries | Talkowski ME , et al. (2012) | Yes | - |
| 3 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 4 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
| 5 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 6 | Recent Recommendation | Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci | Sanders SJ , et al. (2015) | Yes | - |
| 7 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies | Redin C , et al. (2016) | No | - |
| 8 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
| 9 | Support | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
| 10 | Support | Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients | Balicza P , et al. (2019) | Yes | - |
| 11 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 12 | Support | - | Kwong AK et al. (2021) | No | - |
| 13 | Support | - | Yap CX et al. (2021) | Yes | - |
| 14 | Support | - | Abe-Hatano C et al. (2021) | No | - |
| 15 | Support | - | Yuan B et al. (2023) | Yes | - |
| 16 | Support | - | Wang J et al. (2023) | Yes | - |
| 17 | Support | - | et al. () | No | - |
Rare Variants (16)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_gain | Unknown | - | - | 33568206 | Yap CX et al. (2021) | |
| - | - | inversion | De novo | - | - | 22521361 | Talkowski ME , et al. (2012) | |
| - | - | inversion | Unknown | Not maternal | - | 27841880 | Redin C , et al. (2016) | |
| c.1496G>A | p.Arg499His | missense_variant | Unknown | - | - | 37943464 | et al. () | |
| c.983T>C | p.Ile328Thr | missense_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| c.586+23A>T | - | intron_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.586+24T>C | - | intron_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.281G>T | p.Gly94Val | missense_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.1250_1252del | p.Glu417del | inframe_deletion | De novo | - | - | 33446253 | Kwong AK et al. (2021) | |
| c.1625A>G | p.Asp542Gly | missense_variant | Familial | Maternal | - | 31134136 | Balicza P , et al. (2019) | |
| c.1496G>A | p.Arg499His | missense_variant | Familial | - | Unknown | 33624935 | Abe-Hatano C et al. (2021) | |
| c.1180del | p.Ala394GlnfsTer2 | frameshift_variant | De novo | - | Simplex | 22495311 | Neale BM , et al. (2012) | |
| c.657dup | p.Cys220MetfsTer24 | frameshift_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.1492_1493del | p.Arg498AlafsTer13 | frameshift_variant | Familial | Paternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.1775T>G | p.Ile592Arg | missense_variant | De novo | - | Unknown | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| NM_199436.1:c.1149_1153insGTGA;c.1245_1249insGTGA | p.Pro384ValfsTer11 | frameshift_variant | Unknown | - | Simplex | 28263302 | C Yuen RK et al. (2017) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence
Score Delta: Score remained at 1
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
4/1/2021
Score remained at 1
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
1/1/2021
Score remained at 1
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
1/1/2020
Score remained at 1
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
10/1/2019
Decreased from 2 to 1
New Scoring Scheme
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 2 to 2
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
1/1/2019
Decreased from 2 to 2
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
4/1/2017
Decreased from 2 to 2
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
Reports Added
[Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.2012] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017]10/1/2016
Decreased from 2 to 2
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
1/1/2016
Decreased from 2 to 2
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
Reports Added
[Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.2012] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015]10/1/2015
Decreased from 3 to 2
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768). This gene was recently 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).
1/1/2015
Decreased from 3 to 3
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768).
10/1/2014
Decreased from 6 to 3
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD. Two de novo LoF variants in the SPAST gene (both frameshift) have been identified in ASD probands (PMIDs 22495311, 25363768).
7/1/2014
Increased from No data to 6
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD.
4/1/2014
Increased from No data to 6
Description
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 (PMID 22521361). This report also showed that there is no significant burden (P=0.27) of SPAST CNVs in individuals with NDD.
Krishnan Probability Score
Score 0.52194958044536
Ranking 1670/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99707471255289
Ranking 1357/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.982
Ranking 42/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.022256429756575
Ranking 35/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 3
Ranking 362/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.36983984625133
Ranking 1789/20870 scored genes
[Show Scoring Methodology]