Here, we identified a critical activating mutation in SMARCA4 (R1157W) that increased the binding capability of SMARCA4 to PRMT1-mediated H4R3me2a and enhanced the ATPase activity and chromatin remodeling of the SWI/SNF complex, leading to the higher transcriptional output of EGFR and TNS4 to accelerate the progression of CRC. The gene discussed is DNAH8; the disease is colorectal carcinoma.