The EP400 gene encodes a subunit of the NuA4 histone acetyltransferase (HAT) complex, which is responsible for carrying out the acetylation of the nucleosomal histones H2A and H4. This modification is believed to help activate the transcription of certain genes, presumably by altering nucleosome-DNA interactions and promoting the association of the modified histones with other transcription-regulating proteins. Genes suspected to be targeted for transcriptional activation by this complex include E2F1 and MYC during cellular proliferation as well as ZNF42.
The EP400 gene is located on the long arm of chromosome 12. It spans a length of 131 kb of DNA and its coding sequence is spread across 53 exons. The gene encodes a 343.4 kDa protein product comprised of 3159 amino acids. Several additional isoforms of the EPB41L5 gene exist due to alternatively spliced transcript variants. While EP400 is ubiquitously expressed, overexpression of the gene is seen in peripheral blood mononuclear cells, CD8 T-cells, lymph node, B lymphocytes and placenta.
Monies et al. (2017) described the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 5-year-old male from a consanguineous family, presented with global developmental delay, epilepsy and congenital heart disease. Using whole exome sequencing, a heterozygous mutation (c.8226_8227insGCAACAG, p.Q2742fs) was identified in exon 47 of the patient’s EP400 gene. It was considered a candidate for pathogenicity as it was a novel truncating variant and because of EP400’s role as a chromatin modulator (a class of genes often implicated in intellectual disability and heart disease). The authors noted the need for independent confirmation of this association.
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