LOF mutations in PCSK9 gene increase the concentration of LDLR on the cell surface, which promotes the uptake of serum LDL-C and prevents the procession of CAD.GOF mutations enhance the degradation of LDLR, which reduces the uptakes of LDL-C and ultimately increases the circulating LDL-C levels. The gene discussed is COG2; the disease is coronary artery disorder.