WP5109 - Familial hyperlipidemia type 2 - Homo sapiens

Familial hyperlipidemias are grouped according to the Fredrickson classification. Type II familial hyperlipidemia is divided into 2 subtypes, IIa and IIb.
IIa is linked with mutations in the LDL receptor (LDLR) or genes that regulate the LDL uptake. Therefore, we see an increase of LDL with type IIa familial hyperlipidemia. IIa can be subdivided into 4 different types. FHCL1 is caused by direct mutations of LDLR. FCHL1 has different associated phenotypes, caused by mutations in APOA2, EPHX2, and GHR. FCHL2 is caused by mutations in APOB, which acts as a ligand for LDLR. FHCL3 is caused by mutations in PCSK9 which binds to LDLR to inhibit LDL uptake. Lastly, FHCL4 is linked with mutations in LDLRAP1, which stimulates receptor binding.
Type IIB familial hyperlipidemia is known as familial combined hyperlipidemia. This type has shown an increase of both LDL and VLDL. Type IIB can be divided into 3 subtypes. FCHL1 is caused by mutations in USF1 which plays a role in transcription. However, it is unclear exactly how this is linked to lipid metabolism. HYPLIP2 is caused by mutations in APOB, which is linked to reduced LDL. APOB is also a primary apolipoprotein for VLDL. Lastly, FCHL3 is linked to LPL mutations, which is mostly linked to hydrolyzing VLDL into IDL.