MYH9myosin heavy chain 9
Autism Reports / Total Reports
6 / 8Rare Variants / Common Variants
54 / 0Aliases
MYH9, BDPLT6, DFNA17, EPSTS, FTNS, MATINS, MHA, NMHC-II-A, NMMHC-IIA, NMMHCAAssociated Syndromes
-Chromosome Band
22q12.3Associated Disorders
DD/NDDRelevance to Autism
De novo missense variants in the MYH9 gene have been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014) and the SPARK cohort (Wang et al., 2020), as well as in probands from the German Mental Retardation Network (Rauch et al., 2012) and the Deciphering Developmental Disorders 2017 study. Single-molecular molecular inversion probe (smMIP) sequencing of 3,363 probands from cohorts with a primary diagnosis of ASD in Wang et al., 2020 identified 26 individuals with missense variants with CADD scores 30 in the MYH9 gene. A rare coding-synonymous variant in the MYH9 gene was identifed within a risk haplotype on chromosome 22 that co-segregated with ASD in a large, 47-member, multigenerational pedigree with 11 cases of autism spectrum disorder (Marchani et al., 2012). Functional analysis of the ASD-associated p.Arg1571Gln missense variant, which was originally identified in an SSC proband, in Drosophila in Marcogliese et al., 2022 demonstrated a gain-of-function effect (increased lethality when overexpressed compared to reference protein; a gain-of-function effect was also observed in wing-size-based-assay).
Molecular Function
This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness.
External Links
SFARI Genomic Platforms
Reports related to MYH9 (8 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study | Rauch A , et al. (2012) | No | - |
| 2 | Support | Identification of rare variants from exome sequence in a large pedigree with autism | Marchani EE et al. (2012) | Yes | - |
| 3 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 4 | Support | Prevalence and architecture of de novo mutations in developmental disorders | et al. (2017) | No | - |
| 5 | Primary | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | DD |
| 6 | Support | - | Marcogliese PC et al. (2022) | Yes | - |
| 7 | Support | - | Zhou X et al. (2022) | Yes | - |
| 8 | Support | - | Wang J et al. (2023) | Yes | - |
Rare Variants (54)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.-19-7C>A | - | splice_region_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.166G>A | p.Val56Met | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.575C>T | p.Ala192Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.934G>A | p.Gly312Arg | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.943G>T | p.Asp315Tyr | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.506C>G | p.Ser169Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1048G>A | p.Gly350Ser | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1088C>T | p.Ala363Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1279C>T | p.Arg427Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2269G>A | p.Gly757Ser | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2369G>A | p.Cys790Tyr | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.3101A>C | p.Glu1034Ala | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3914C>T | p.Ala1305Val | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.4726C>T | p.Arg1576Trp | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.4771G>A | p.Val1591Met | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5692C>T | p.Arg1898Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3547C>T | p.His1183Tyr | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1933A>G | p.Thr645Ala | missense_variant | De novo | - | Simplex | 28135719 | et al. (2017) | |
| c.3195C>T | p.Ala1065%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3756G>A | p.Ala1252%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3816C>T | p.Ala1272%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4407G>A | p.Ala1469%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.5277C>T | p.Ile1759%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.934G>A | p.Gly312Arg | missense_variant | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
| c.5189G>A | p.Arg1730His | missense_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.5693G>A | p.Arg1898His | missense_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
| c.5707G>A | p.Ala1903Thr | missense_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
| c.5089A>T | XP_005261671.1:p.Lys1697Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4712G>A | p.Arg1571Gln | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.73G>A | p.Asp25Asn | missense_variant | Familial | Paternal | Simplex | 33004838 | Wang T et al. (2020) | |
| c.2140C>T | XP_005261671.1:p.Arg714Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2257G>A | XP_005261671.1:p.Gly753Ser | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2311G>A | XP_005261671.1:p.Asp771Asn | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2570C>A | XP_005261671.1:p.Pro857Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3166C>T | XP_005261671.1:p.Arg1056Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3278C>T | XP_005261671.1:p.Ala1093Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3736G>A | XP_005261671.1:p.Glu1246Lys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4027C>T | XP_005261671.1:p.Arg1343Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4028G>A | XP_005261671.1:p.Arg1343Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4511G>A | XP_005261671.1:p.Arg1504Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4789C>T | XP_005261671.1:p.Arg1597Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4838G>A | XP_005261671.1:p.Arg1613Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5311G>A | XP_005261671.1:p.Asp1771Asn | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5725C>T | XP_005261671.1:p.Arg1909Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5743C>T | XP_005261671.1:p.Arg1915Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4361G>A | XP_005261671.1:p.Arg1454His | missense_variant | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
| c.2279C>T | XP_005261671.1:p.Ala760Val | missense_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.3709G>A | XP_005261671.1:p.Glu1237Lys | missense_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
| c.4027C>T | XP_005261671.1:p.Arg1343Trp | missense_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.4838G>A | XP_005261671.1:p.Arg1613Gln | missense_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.5018G>A | XP_005261671.1:p.Arg1673His | missense_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
| c.5758G>A | XP_005261671.1:p.Glu1920Lys | missense_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
| c.4008C>T | p.Asp1336%3D | synonymous_variant | Familial | - | Extended multiplex | 23594493 | Marchani EE et al. (2012) | |
| c.3736G>A | XP_005261671.1:p.Glu1246Lys | missense_variant | Familial | Maternal | Simplex | 33004838 | Wang T et al. (2020) |
Common Variants
No common variants reported.
SFARI Gene score
2
Strong Candidate
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Increased from to 2
Krishnan Probability Score
Score 0.49547779911135
Ranking 2943/25841 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 0.99999999991202
Ranking 70/18225 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
Iossifov Probability Score
Score 0.97
Ranking 58/239 scored genes
[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists
239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This
probability metric combines the evidence from de novo likely-gene- disrupting and missense
mutations and assesses it against the background mutation rate in unaffected individuals from the
University of Washingtonâs Exome Variant Sequence database (evs.gs.washington.edu/EVS/).
The list of probability scores can be found here:
www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/-
/DCSupplemental/pnas.1516376112.sd02.xlsx
Sanders TADA Score
Score 0.9508516897421
Ranking 18653/18665 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 0.36160153166721
Ranking 1883/20870 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.