TMED4 and hepatocellular carcinoma: For the hepatocellular carcinoma pathway (Figure 7), WINNER expansion added KC1G2, a serine-threonine kinase that can activate TGF-β1/Smad signaling (Guo et al., 2008); TMED4, WLS, and PRCN, which mediate Wnt/β-catenin signaling (Guo et al., 2008; Martin-Orozco et al., 2019; Bland et al., 2021); and several genes for proteins in the FGF signaling pathway (FRS2, FRS3, KLB, and PLCG1; Gotoh, 2008; Gyanchandani et al., 2013; Wang et al., 2020), of which KLB is particularly important, because it functions as a co-receptor for the binding of FGF-19/21 to FGFR-1/4 (Yang et al., 2012).