It was found that nearly a quarter of the 447 colon adenocarcinoma samples had mutations in at least one key FAM gene, and LRP2 exhibited the highest frequency, while there were no mutations in PLAAT5 and TNFAIP8L3. Missense mutation was the main variant type of the screened FAM genes, which is consistent with the general mutation features of colon cancer. Here, PLAAT5 is linked to malignant colon neoplasm.