Human Gene Module / Chromosome 15 / MAP1A

MAP1Amicrotubule associated protein 1A

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
1 / 0
Aliases
MAP1A, MAP1L,  MTAP1A
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
15q15.3
Associated Disorders
-
Relevance to Autism

Large sample resequencing of 408 selected brain-expressed genes in a cohort of 142 ASD cases and 142 schizophrenia cases in Myers et al., 2011 found that MAP1A had a significant excess of rare missense variants in both disease cohorts. Analysis of exome sequencing data from approximately 8,000 children with ASD and/or ADHD and 5,000 controls from the iPSYCH research initiative in Satterstrom et al., demonstrated that MAP1A had an excess of rare protein-truncating variants in cases compared to controls (11 in cases vs. 0 in controls; p-value 9.21E-03) and subsequently reached exome-wide significance following the inclusion of gnomAD data and Bonferroni correction (combined p-value 4.11E-07, odds ratio 16.4). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified MAP1A as a candidate gene with a false discovery rate (FDR) 0.01.

Molecular Function

This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1A heavy chain and LC2 light chain. Expression of this gene is almost exclusively in the brain. Studies of the rat microtubule-associated protein 1A gene suggested a role in early events of spinal cord development.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MAP1A (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A population genetic approach to mapping neurological disorder genes using deep resequencing Myers RA , et al. (2011) Yes -
2 Recent recommendation Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants Satterstrom FK , et al. (2019) Yes -
3 Recent recommendation Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Support - Woodbury-Smith M et al. (2022) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.4163A>G p.Tyr1388Cys missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We 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.

4/1/2022
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1

Increased from to 1

Krishnan Probability Score

Score 0.63433212994668

Ranking 60/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99968899760248

Ranking 846/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94941698708888

Ranking 18082/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.37270886123888

Ranking 1760/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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