Although the role of these domains remains elusive, our functional studies support a function in the splicing mechanism with the p.R35L mutation leading to alternative splice site usage in known target genes such as the transcriptional corepressor BCOR, associated with poor prognosis in MDS when altered [77], or the H3K4 methyltransferase KMT2D/MLL2 that have been show to play a role in hematopoiesis [78]. The gene discussed is KMT2D; the disease is myelodysplastic syndrome.