Human Gene Module / Chromosome 17 / MAPT

MAPTmicrotubule associated protein tau

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
2 / 1
Aliases
MAPT, DDPAC,  FTDP-17L,  MSTD,  MTBT1,  MTBT2,  PPND,  PPP1R103,  TAU,  tau-40, MAPT
Associated Syndromes
-
Chromosome Band
17q21.31
Associated Disorders
-
Relevance to Autism

An intronic SNP in the MAPT gene (rs141455452) was found to be significantly associated with ASD (P-value 9.0E-07) in a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) in Grove et al., 2019. A transcriptome-wide association study (TWAS) of 7,805 ASD proband-parent trios, which was subsequently replicated using 35,740 independent samples, using eQTL and splicing quantitative trait loci in 12 brain tissues from GTEx and the CommonMind Consortium (CMC) in Huang et al., 2021 identified MAPT as a gene whose transcriptome-wide association with ASD remained significant after a stringent Bonferroni correction for all genes and all tissues in the analysis (meta-analysis P-value 5.67E-09 in CMC DLPFC-splicing tissue).

Molecular Function

This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MAPT (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Identification of common genetic risk variants for autism spectrum disorder Grove J , et al. (2019) Yes -
2 Support - Huang K et al. (2021) Yes -
3 Support - Rosenthal SB et al. (2021) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
5 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.445G>A p.Ala149Thr missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.1342C>T p.Arg448Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-17-20604T>G;c.-170-19888T>G - intron_variant - - - 30804558 Grove J , et al. (2019)
SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.75841324445215

Ranking 31/25841 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 4.6826496228243E-5

Ranking 13488/18225 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 0.63537540354752

Ranking 836/18665 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 0.43525299142093

Ranking 1076/20870 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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