Among the top ten mutated genes, ATP1A1, C1orf159 have been reported to be associated with ESCC development, and other novel mutated genes we identified, such as AGRN, TNFRSF8, BRINP3, ATAD3A, ARHGEF16, ARF4, AMY1A, AGO1, have been studied in some diseases, but lacking a study with ESCC (Figure 3F). Here, ARHGEF16 is linked to esophageal squamous cell carcinoma.