Relevance 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

References