Human Gene Module / Chromosome 17 / MYH10

MYH10myosin heavy chain 10

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 8
Rare Variants / Common Variants
12 / 0
Aliases
MYH10, NMMHC-IIB,  NMMHCB
Associated Syndromes
-
Chromosome Band
17p13.1
Associated Disorders
-
Relevance to Autism

Three rare de novo variants in the MYH10 gene (one loss-of-function, two missense variants predicted to be damaging) have been identified in ASD probands from the Simons Simplex Collection (Willsey et al., 2013; Iossifov et al., 2014). Functional analysis of the ASD-associated p.Tyr265Cys variant in transfected primary rat hippocampal neurons in Hlushchenko et al., 2018 (PMID 30123108) demonstrated that this variant reduced the size of inhibitory synapses and reduced the density of inhibitory synapses in spines of transfected hippocampal neurons compared to wild-type protein, with no other effects on localization, dendritic spine density or morphology. De novo variants in this gene have also been observed in individuals presenting with developmental delay, microcephaly, and cerebral atrophy (Tuzovic et al., 2013; Hamdan et al., 2014).

Molecular Function

This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-10 (MYO10). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene have been associated with May-Hegglin anomaly and developmental defects in brain and heart.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MYH10 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism Willsey AJ , et al. (2013) Yes -
2 Support A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice Tuzovic L , et al. (2013) No -
3 Support De novo mutations in moderate or severe intellectual disability Hamdan FF , et al. (2014) No -
4 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
5 Recent Recommendation ASD-Associated De Novo Mutations in Five Actin Regulators Show Both Shared and Distinct Defects in Dendritic Spines and Inhibitory Synapses in Cultured Hippocampal Neurons Hlushchenko I , et al. (2018) No -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Hu C et al. (2023) Yes -
8 Support - Kipkemoi P et al. (2023) Yes -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.4209+6C>T - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.1313C>T p.Thr438Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3246G>T p.Gln1082His missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5772G>A p.Ala1924%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
GA>G 755-! frameshift_variant De novo - Simplex 24267886 Willsey AJ , et al. (2013)
c.983C>T p.Pro328Leu missense_variant Familial Maternal - 37007974 Hu C et al. (2023)
c.2722G>T p.Glu908Ter stop_gained De novo - Simplex 25003005 Tuzovic L , et al. (2013)
c.1690del p.Val564PhefsTer16 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.242C>T p.Pro81Leu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.838C>T p.Arg280Cys missense_variant De novo - Simplex 25356899 Hamdan FF , et al. (2014)
c.794A>G p.Tyr265Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2555G>A p.Arg852Gln missense_variant De novo - Simplex 37463579 Kipkemoi P et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Three rare de novo variants in the MYH10 gene (one loss-of-function, two missense variants predicted to be damaging) have been identified in ASD probands from the Simons Simplex Collection (Willsey et al., 2013; Iossifov et al., 2014). Functional analysis of the ASD-associated p.Tyr265Cys variant in transfected primary rat hippocampal neurons in Hlushchenko et al., 2018 (PMID 30123108) demonstrated that this variant reduced the size of inhibitory synapses and reduced the density of inhibitory synapses in spines of transfected hippocampal neurons compared to wild-type protein, with no other effects on localization, dendritic spine density or morphology. De novo variants in this gene have also been observed in individuals presenting with developmental delay, microcephaly, and cerebral atrophy (Tuzovic et al., 2013; Hamdan et al., 2014).

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

Three rare de novo variants in the MYH10 gene (one loss-of-function, two missense variants predicted to be damaging) have been identified in ASD probands from the Simons Simplex Collection (Willsey et al., 2013; Iossifov et al., 2014). Functional analysis of the ASD-associated p.Tyr265Cys variant in transfected primary rat hippocampal neurons in Hlushchenko et al., 2018 (PMID 30123108) demonstrated that this variant reduced the size of inhibitory synapses and reduced the density of inhibitory synapses in spines of transfected hippocampal neurons compared to wild-type protein, with no other effects on localization, dendritic spine density or morphology. De novo variants in this gene have also been observed in individuals presenting with developmental delay, microcephaly, and cerebral atrophy (Tuzovic et al., 2013; Hamdan et al., 2014).

Reports Added
[New Scoring Scheme]
7/1/2018
icon
3

Increased from to 3

Description

Three rare de novo variants in the MYH10 gene (one loss-of-function, two missense variants predicted to be damaging) have been identified in ASD probands from the Simons Simplex Collection (Willsey et al., 2013; Iossifov et al., 2014). Functional analysis of the ASD-associated p.Tyr265Cys variant in transfected primary rat hippocampal neurons in Hlushchenko et al., 2018 (PMID 30123108) demonstrated that this variant reduced the size of inhibitory synapses and reduced the density of inhibitory synapses in spines of transfected hippocampal neurons compared to wild-type protein, with no other effects on localization, dendritic spine density or morphology. De novo variants in this gene have also been observed in individuals presenting with developmental delay, microcephaly, and cerebral atrophy (Tuzovic et al., 2013; Hamdan et al., 2014).

Krishnan Probability Score

Score 0.60027537035587

Ranking 403/25841 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 0.99999754972767

Ranking 356/18225 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 0.12933841256199

Ranking 77/18665 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 0.38800140728517

Ranking 1589/20870 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
Submit New Gene

Report an Error