Human Gene Module / Chromosome 19 / MAST1

MAST1microtubule associated serine/threonine kinase 1

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
20 / 0
Aliases
-
Associated Syndromes
Mega-corpus-callosum syndrome with cerebellar hypo
Chromosome Band
19p13.13
Associated Disorders
-
Relevance to Autism

"A de novo missense variant in the MAST1 gene with a CADD score of 26.9 was identified in a male patient from the Solve-RD resource with the HPO phenoterm ""Autism"" in Laurie et al., 2025. Two de novo loss-of-function variants and seven de novo missense variants (2 with CADD >25) in this gene have been reported in ASD probands from the Autism Sequencing Consortium and the SPARK and MSSNG cohorts (Lim et al., 2017; Zhou et al., 2022; Fu et al., 2022). In a report describing six patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM; OMIM 618273), Tripathy et al., 2018 also described two individuals identified via GeneMatcher with de novo MAST1 missense variants and ASD with additional features (speech delay/absent speech, ID, hypotonia, and dysmorphic features) but without significant findings on brain imaging."

Molecular Function

This gene is a member of the microtubule-associated serine/threonine kinase (MAST) family. The protein encoded by this gene has an N-terminal serine/threonine kinase domain followed by a postsynaptic density protein-95/discs large/zona occludens-1 (PDZ) domain. In mouse and rat, the orthologous protein associates with the cytoskeleton and can bind both beta-2-syntrophin and neuronal nitric oxide synthase (nNOS) through its PDZ domain. In mouse and rat, this protein also co-localizes with dystrophin- and utrophin-associated protein complexes (DAPC/UAPC) in the vascular endothelium of the central nervous system.

External Links
Gene CardPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser
Reports related to MAST1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
2 Support - Ratna Tripathy et al. (2018) No ASD, epilepsy/seizures
3 Support - Zhou X et al. (2022) Yes -
4 Support - Fu JM et al. (2022) Yes -
5 Primary - Steven Laurie et al. (2025) Yes -
Rare Variants   (20)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.74G>A p.Arg25His missense_variant De novo - - 35982160 Fu JM et al. (2022)
c.1217A>G p.Asn406Ser missense_variant De novo - - 35982160 Fu JM et al. (2022)
c.3241T>C p.Ser1081Pro missense_variant De novo - - 28714951 Lim ET , et al. (2017)
c.2139+1G>A p.? splice_site_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2527C>T p.Gln843Ter stop_gained De novo - Multiplex 35982159 Zhou X et al. (2022)
c.278C>T p.Ser93Leu missense_variant De novo - - 30449657 Ratna Tripathy et al. (2018)
c.293G>T p.Gly98Val missense_variant De novo - - 30449657 Ratna Tripathy et al. (2018)
c.858G>A p.Ala286= synonymous_variant De novo - Unknown 35982159 Zhou X et al. (2022)
c.3264-5C>T p.? splice_region_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1576C>T p.Leu526Phe missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2864G>A p.Arg955Gln missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1549G>A p.Gly517Ser missense_variant De novo - - 30449657 Ratna Tripathy et al. (2018)
c.2743G>A p.Ala915Thr missense_variant De novo - - 30449657 Ratna Tripathy et al. (2018)
c.709G>A p.Asp237Asn missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3530C>G p.Pro1177Arg missense_variant De novo - - 30449657 Ratna Tripathy et al. (2018)
c.4306A>G p.Ile1436Val missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.583_585del p.Glu195del inframe_deletion De novo - - 30449657 Ratna Tripathy et al. (2018)
c.829_831del p.Lys277del inframe_deletion De novo - - 30449657 Ratna Tripathy et al. (2018)
c.832_834del p.Leu279del inframe_deletion De novo - - 30449657 Ratna Tripathy et al. (2018)
c.1762T>G p.Phe588Val missense_variant De novo - Simplex 39825153 Steven Laurie et al. (2025)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

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.

7/1/2025
3

Initial score established: 3

Krishnan Probability Score

Score 0.49521173971829

Ranking 3120/25841 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 0.99999902438586

Ranking 298/18225 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 0.94922247741748

Ranking 18003/18665 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 0.088391910462372

Ranking 6361/20870 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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