Human Gene Module / Chromosome 19 / MYO9B

MYO9BMyosin IXB

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
34 / 0
Aliases
MYO9B, CELIAC4,  MYR5
Associated Syndromes
-
Chromosome Band
19p13.11
Associated Disorders
-
Relevance to Autism

This gene was identified in an ASD whole-exome sequencing study and subsequent TADA (transmission and de novo association) analysis as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (De Rubeis et al., 2014).

Molecular Function

his gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins that may be involved in the remodeling of the actin cytoskeleton. The protein represents an unconventional myosin, which serve in intracellular movements. Polymorphisms in this gene are associated with susceptibility to celiac disease.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MYO9B (6 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 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 -
4 Support Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort Callaghan DB , et al. (2019) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Hu C et al. (2023) Yes -
Rare Variants   (34)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.*12G>A - 3_prime_UTR_variant De novo - - 35982159 Zhou X et al. (2022)
c.1300G>A p.Val434Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1711G>A p.Gly571Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2118C>T p.Ala706%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1159G>A p.Ala387Thr missense_variant Familial Paternal - 37007974 Hu C et al. (2023)
c.597C>T p.Tyr199%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.4393C>T p.Arg1465Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.400C>T p.Arg134Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5615A>G p.Lys1872Arg missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.1063C>T p.Leu355Phe missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2671G>A p.Ala891Thr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3940C>T p.Arg1314Trp missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.4094C>T p.Pro1365Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4507C>T p.Arg1503Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4717G>A p.Val1573Ile missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4747A>G p.Lys1583Glu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4858A>C p.Lys1620Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5164C>T p.His1722Tyr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5577C>A p.Asp1859Glu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.6005C>T p.Ser2002Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5575G>A p.Asp1859Asn missense_variant Unknown - Simplex 31038196 Callaghan DB , et al. (2019)
c.281G>A p.Arg94Gln missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1825G>A p.Ala609Thr missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2077C>T p.Arg693Trp missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2104G>A p.Gly702Arg missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2107C>T p.Arg703Cys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3451C>T p.Arg1151Cys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3454C>T p.Arg1152Trp missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4135G>A p.Gly1379Arg missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4217C>T p.Pro1406Leu missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4717G>A p.Val1573Ile missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.6040G>A p.Gly2014Arg missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4491dup p.Arg1498AlafsTer13 frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.2027G>T p.Gly676Val missense_variant Familial Paternal Multiplex 25363760 De Rubeis S , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo LoF variant and two de novo missense variants that are predicted to be damaging were identified in the MYO9B gene in ASD probands (PMID 22542183, 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYO9B as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760).

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

A de novo LoF variant and two de novo missense variants that are predicted to be damaging were identified in the MYO9B gene in ASD probands (PMID 22542183, 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYO9B as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760).

Reports Added
[New Scoring Scheme]
4/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant and two de novo missense variants that are predicted to be damaging were identified in the MYO9B gene in ASD probands (PMID 22542183, 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYO9B as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760).

Reports Added
[Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.2019]
7/1/2018
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant and two de novo missense variants that are predicted to be damaging were identified in the MYO9B gene in ASD probands (PMID 22542183, 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYO9B as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760).

Reports Added
[ASD-Associated De Novo Mutations in Five Actin Regulators Show Both Shared and Distinct Defects in Dendritic Spines and Inhibitory Synapses in Cult...2018]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant and two de novo missense variants that are predicted to be damaging were identified in the MYO9B gene in ASD probands (PMID 22542183, 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYO9B as a gene meeting high statistical significance with a 0.05

Reports Added
[Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014]
10/1/2014
icon
3

Increased from to 3

Description

A de novo LoF variant and two de novo missense variants that are predicted to be damaging were identified in the MYO9B gene in ASD probands (PMID 22542183, 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYO9B as a gene meeting high statistical significance with a 0.05

Krishnan Probability Score

Score 0.4932049274305

Ranking 4244/25841 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 0.99999887709674

Ranking 309/18225 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 0.17741906628855

Ranking 99/18665 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
Larsen Cumulative Evidence Score

Score 36.5

Ranking 57/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.049744369498752

Ranking 7241/20870 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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