Relevance to Autism

De novo likely gene-disruptive (LGD) variants in the SET gene have been identifed in two probands with ASD (Yuen et al., 2017) and three probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SET as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) that passed a Bonferroni family-wise error rare (FWER) correction indicating exome-wide significance (P < 5.0E-07); SET was similarly identified as a gene with an excess of de novo LGD variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018). Stevens et al., 2018 identified four individuals with de novo SET variants, as well as an affected mother and son with a SET frameshift variant, who presented with non-syndromic intellectual disability (autosomal dominant mental retardation-58; OMIM 618106).

Molecular Function

The protein encoded by this gene inhibits acetylation of nucleosomes, especially histone H4, by histone acetylases (HAT). This inhibition is most likely accomplished by masking histone lysines from being acetylated, and the consequence is to silence HAT-dependent transcription. Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning.

External Links

References