WT-like variants displayed immune system and cell-cycle-related functions (patterns 4 and 1), positive regulation of T cell lineage commitment, proliferation, and activation specifically (program 4), consistent with the role of RUNX1 in hematopoietic lineage commitment and differentiation.20,44,69,73,74 LoF-like variants upregulated heme biosynthesis (program 1 and pattern 3), angiogenesis (program 2), and extracellular matrix regulation (program 3), which is consistent with a shift toward erythroid differentiation49,50 and hematological malignancies,73,75 with loss of RUNX1 activity. The gene discussed is RUNX1; the disease is hematologic disorder.