ASXL1 mutants were shown to impair the association of wild-type ASXL1 with BAP1 in a dominant-negative manner by sequestering the enzyme and suppressing its recruitment to the promoters of FOXK1/K2 target genes, thereby leading to the maintenance of H2AK119Ub1 levels; deleting mutated ASXL1 restored the expression of BAP1-ASXL1-FOXK1/K2 target genes that play a role in hematopoiesis and/or tumor suppression (e.g., VHL, SOCS1/2, and TXNIP). The gene discussed is ASXL1; the disease is neoplasm.