Relevance to Autism

Two de novo missense variants in the SMARCA4 gene were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014; both of these variants were later determined to be postzygotic mosaic mutations (PZMs) in Lim et al., 2017. A third non-synonymous PZM in SMARCA4 was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (3/571 observed vs. 11/84,448 expected; hypergeometric P-value of 4.9E-05). Furthermore, Lim et al., 2017 demonstrated that overexpression of SMARCA4 mutants in mouse neuroblastoma (N2A) cells resulted in significantly lower expression of GRIN2B compared to wild-type SMARCA4.

Molecular Function

The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. Mutations in this gene are associated with Coffin-Siris syndrome 4 (CSS4; OMIM 614609).

External Links

References