Similarly, the Cul4A-DDB1 E3 ligase complex induces PHGDH K146 monoubiquitination, enhancing PHGDH enzyme activity from mutant low-activity PHGDH K146R, which promotes CRC metastasis progression by increasing intracellular S-adenosylmethionine levels and initiating SETD1A-mediated histone methylation of LAMC2 and CYR61[110]. The gene discussed is PHGDH; the disease is colorectal carcinoma.