Based on our results from PBC&PSC pathogenesis, we identified that the DNA methylation profile changes for RPL23A and HIST2H2BE result in dysfunctions in the autoimmune and DNA repair response to progression from normal liver cells to PBC&PSC and give rise to the dysregulation of RYR2 through the WNT and the MAPK signaling pathways, to facilitate defects in autoimmunity as shown in Figure 7. The gene discussed is RYR2; the disease is primary biliary cholangitis.