The majority of CH is caused by mutations in a limited set of genes (Figure 1), predominately those involved in epigenetic regulation (DNMT3A, TET2, and ASXL1), signal transduction (JAK2), splicing (SF3B1, SRSF2, and U2AF1), and the DNA damage response (DDR; TP53 and PPM1D). This evidence concerns the gene U2AF1 and cyclic hematopoiesis.