Out of these significantly mutated genes, twelve - RYR2, PIK3CA, ABCA13, SI, RYR3, MGAM, CUBN, HCN1, CACNA1H, ADCY2, ABCA4, PTEN, and ADCY8 - had recurrent mutations, confirming their involvement in ESCC (Figure 1A, Table S5). Here, RYR3 is linked to esophageal squamous cell carcinoma.