Human Gene Module / Chromosome 15 / MYO1E

MYO1Emyosin IE

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
9 / 0
Aliases
MYO1E, FSGS6,  HuncM-IC,  MYO1C
Associated Syndromes
-
Chromosome Band
15q22.2
Associated Disorders
-
Relevance to Autism

A de novo loss-of-function (LoF) variant and two de novo missense variants (one of which was not present in external databases and was predicted in silico to be damaging) were identified in the MYO1E gene in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified MYO1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

Molecular Function

This gene encodes a member of the nonmuscle class I myosins which are a subgroup of the unconventional myosin protein family. The unconventional myosin proteins function as actin-based molecular motors. Class I myosins are characterized by a head (motor) domain, a regulatory domain and a either a short or long tail domain. Among the class I myosins, this protein is distinguished by a long tail domain that is involved in crosslinking actin filaments. This protein localizes to the cytoplasm and may be involved in intracellular movement and membrane trafficking. Mutations in this gene are the cause of focal segmental glomerulosclerosis-6.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MYO1E (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
3 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Support - Woodbury-Smith M et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2134C>T p.Arg712Trp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2459G>A p.Arg820Gln missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3163C>T p.Gln1055Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1807G>C p.Val603Leu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.751G>A p.Asp251Asn missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1376T>G p.Ile459Ser missense_variant De novo - - 35205252 Woodbury-Smith M et al. (2022)
c.1109C>G p.Ser370Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.511-2A>G - splice_site_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2383G>A p.Gly795Arg missense_variant Unknown Not maternal Simplex 30564305 Guo H , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo loss-of-function (LoF) variant and two de novo missense variants (one of which was not present in external databases and was predicted in silico to be damaging) were identified in the MYO1E gene in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified MYO1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A de novo loss-of-function (LoF) variant and two de novo missense variants (one of which was not present in external databases and was predicted in silico to be damaging) were identified in the MYO1E gene in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified MYO1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo loss-of-function (LoF) variant and two de novo missense variants (one of which was not present in external databases and was predicted in silico to be damaging) were identified in the MYO1E gene in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified MYO1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function (LoF) variant and two de novo missense variants (one of which was not present in external databases and was predicted in silico to be damaging) were identified in the MYO1E gene in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified MYO1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

A de novo loss-of-function (LoF) variant and two de novo missense variants (one of which was not present in external databases and was predicted in silico to be damaging) were identified in the MYO1E gene in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified MYO1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

Krishnan Probability Score

Score 0.41081525775783

Ranking 22567/25841 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 0.047977893071742

Ranking 8600/18225 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 0.34501999820545

Ranking 218/18665 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 -0.07216905711684

Ranking 11269/20870 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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