Human Gene Module / Chromosome 15 / MYO5A

MYO5Amyosin VA

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 7
Rare Variants / Common Variants
14 / 1
Aliases
MYO5A, GS1,  MYH12,  MYO5,  MYR12
Associated Syndromes
-
Chromosome Band
15q21.2
Associated Disorders
-
Relevance to Autism

Two de novo missense variants in the MYO5A gene had previously been identified in ASD probands (one proband from the Autism Sequencing Consortium in De Rubeis et al., 2014, the other from the Simons Simplex Collection in Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), MYO5A was determined to be an ASD candidate gene in Yuen et al., 2017.

Molecular Function

This gene is one of three myosin V heavy-chain genes, belonging to the myosin gene superfamily. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MYO5A (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Recent Recommendation Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
4 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - et al. () Yes ADHD
Rare Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3614C>A p.Ser1205Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1826G>A p.Arg609His missense_variant De novo - Simplex 37805537 et al. ()
c.5234A>G p.Glu1745Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5523T>G p.Phe1841Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.368T>G p.Ile123Ser missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1177A>G p.Lys393Glu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2398G>A p.Val800Met missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3768C>T p.Ser1256%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1958C>G p.Thr653Ser missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1961C>A p.Thr654Asn missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1331T>A p.Phe444Tyr missense_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
c.4010C>T p.Ala1337Val missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.4919G>T p.Gly1640Val missense_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
c.4002_4003insGCTGTGGCTGGTTTATGAAGG p.Glu1334_Leu1335insAlaValAlaGlyLeuTer inframe_insertion De novo - - 35982159 Zhou X et al. (2022)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - allele - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
SFARI Gene score
2

Strong Candidate

Two de novo missense variants in the MYO5A gene had previously been identified in ASD probands (one proband from the Autism Sequencing Consortium in De Rubeis et al., 2014, the other from the Simons Simplex Collection in Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), MYO5A was determined to be an ASD candidate gene in Yuen et al., 2017.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two de novo missense variants in the MYO5A gene had previously been identified in ASD probands (one proband from the Autism Sequencing Consortium in De Rubeis et al., 2014, the other from the Simons Simplex Collection in Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), MYO5A was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Two de novo missense variants in the MYO5A gene had previously been identified in ASD probands (one proband from the Autism Sequencing Consortium in De Rubeis et al., 2014, the other from the Simons Simplex Collection in Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), MYO5A was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
4/1/2017
icon
3

Increased from to 3

Description

Two de novo missense variants in the MYO5A gene had previously been identified in ASD probands (one proband from the Autism Sequencing Consortium in De Rubeis et al., 2014, the other from the Simons Simplex Collection in Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), MYO5A was determined to be an ASD candidate gene in Yuen et al., 2017.

Krishnan Probability Score

Score 0.5561858421863

Ranking 1342/25841 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 0.99212966721907

Ranking 1702/18225 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 0.65299929035881

Ranking 909/18665 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 0.50414678935698

Ranking 496/20870 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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