TABLE 3.

Overview of genetic causes of the FH phenotype.

Gene	Protein	Protein function	Mode of inheritance	Resulting effect
LDLR	Low-density lipoprotein receptor	Cell surface receptor that plays an important role in cholesterol homeostasis, transporting cholesterol through cell surface	AD	↓ binding affinity of LDL-receptor protein
APOB	Apolipoprotein B	Major protein of LDL particle, ligand for LDL receptor	AD	↓ binding affinity of APOB to LDL-receptor
PCSK9	Proprotein-convertase subtilisin kexin 9	Protease that plays a role in LDL-receptor degradation	AD	↑ LDL-receptor protein degradation
STAP1	Signal-transducing adaptor protein-1	Unknown	AD	Unknown/incomplete association with hypercholesterolemia
LDLRAP1	Low-density lipoprotein receptor adaptor protein 1	Adaptor protein that interacts with cytoplasmatic tail of LDL receptor, promoting LDL particle internalization	AR	LDL-receptor dysfunction
LIPA	Lysosomal acid lipase alias cholesterol esters lipase	Hydrolysis of cholesterol esters or triglycerides	AR	APOB overproduction, upregulation of HMGCoA reductase
ABCG5/ABCG8	Sterolin-1 and 2	Transporters required for secretion of cholesterol into bile	AR	↑ absorption of plant sterols
PNPLA5	Patatin-like phospholipase domain-containing protein 5	Influencing adipocyte differentiation, triglyceride hydrolysis	AR	Possibly lipolysis impairment

AR, autosomal recessive; AD, autosomal dominant; HMGCoA, hydroxy-methyl glutaryl coenzyme A.