DNMT3A

DNA (cytosine-5)-methyltransferase 3A is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene.

Function

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than the maintenance of existing methylated sites. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. Alternative splicing results in multiple transcript variants encoding different isoforms.

Clinical relevance

The study of this gene in mice has shown its reduced expression in ageing animals causes cognitive long-term memory decline. It is also frequently mutated in cancer, being one of 127 frequently mutated genes identified in the Cancer Genome Atlas project, in a publication involving whole-genome sequencing on 3,281 cancers of various types. In the Cancer Genome Atlas study, DNMT3A mutations were most commonly seen in acute myeloid leukaemia where they occurred in just over 25% of cases sequenced. Mutations were also relatively common in lung cancers.