De novo heterozygous variants in EHMT2 genocopy Kleefstra syndrome via loss of G9a methyltransferase activity

EHMT1 and EHMT2 genes encode human euchromatin histone lysine methyltransferase 1 and 2 (EHMT1 alias GLP; EHMT2 alias G9a) that form heteromeric GLP/G9a complexes with essential roles in epigenetic regulation of gene expression. While EHMT1 haploinsufficiency was established as the cause of Kleefstra syndrome twenty years ago, the pathogenesis of G9a dysfunction in human disease remains largely unknown…

Source: https://www.biorxiv.org/content/10.1101/2025.09.25.678439v1.abstract