In this study, we performed exome analysis of 3 sCRC tumor samples with LoF mutation screening strategy, together with systems-level analysis, we uncovered well-studied tumor suppressor APC, TCF7L2, and ELF3 in CRC, as well as novel top rank gene BMP5 that can affect CRC initiation, progression and prognosis. The gene discussed is ELF3; the disease is neoplasm.