Human Gene Module / Chromosome 17 / MYH4

MYH4Myosin, heavy chain 4, skeletal muscle

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
5 / 0
Aliases
MYH4, MYH2B,  MyHC-2B,  MyHC-IIb
Associated Syndromes
Tourette syndrome
Genetic Category
Rare Single Gene Mutation
Chromosome Band
17p13.1
Associated Disorders
-
Relevance to Autism

A novel recurrent deletion involving the MYH4 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

Molecular Function

Gene product involved muscle contraction

Reports related to MYH4 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder. Prasad A , et al. (2013) Yes -
2 Support Genome-wide characteristics of de novo mutations in autism. Yuen RK , et al. (2016) Yes -
3 Positive Association De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Willsey AJ , et al. (2017) No -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial Maternal Simplex 23275889 Prasad A , et al. (2013)
- - copy_number_loss Familial Maternal Multiplex 23275889 Prasad A , et al. (2013)
c.3595A>G p.Lys1199Glu missense_variant De novo NA Simplex 27525107 Yuen RK , et al. (2016)
c.4109G>C p.Ser1370Thr missense_variant De novo NA Simplex 28472652 Willsey AJ , et al. (2017)
c.1531dup p.Trp511LeufsTer5 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

A novel recurrent deletion involving the MYH4 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

Score Delta: Decreased from 4 to 3

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.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A novel recurrent deletion involving the MYH4 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

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

Decreased from 4 to 4

Description

A novel recurrent deletion involving the MYH4 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

4/1/2017
4
icon
4

Decreased from 4 to 4

Description

A novel recurrent deletion involving the MYH4 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

7/1/2016
4
icon
4

Decreased from 4 to 4

Description

A novel recurrent deletion involving the MYH4 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

7/1/2015
icon
4

Increased from to 4

Description

A novel recurrent deletion involving the MYH4 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

Krishnan Probability Score

Score 0.45747136814236

Ranking 9766/25841 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.
ExAC Score

Score 8.8149213458824E-35

Ranking 18183/18225 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
Sanders TADA Score

Score 0.95049326600726

Ranking 18514/18665 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).
Zhang D Score

Score -0.15861887566291

Ranking 14387/20870 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.
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