Familial hyperlipidemia type 2 (WP5109)

Homo sapiens

Familial hyperlipidemias are classified 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 subdived into 4 different types. FHCL1 is caused by direct mutations of the LDLR. This FCHL1 has different phenotypes linked to it which are cause by mutations in APOA2, EPHX2 and GHR. FCHL2 is caused by mutations in APOB, which acts as a ligand for the 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. Typ 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 cellular transcription. However, it is unclear how exactly this is linked to the lipid metabolism. HYPLIP2 is caused by mutations in APOB, which is linked to the reduced LDL. APOB is also a primmary apolipoprotein for VLDL. Lastly, FCHL3 is linked to LPL mutations, which is mostly linnked to hydrolizing the VLDL into IDL.


Ulas Babayigit and Friederike Ehrhart


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Homo sapiens


Rare Diseases


Disease Ontology

familial hyperlipidemia familial combined hyperlipidemia familial hypercholesterolemia

Pathway Ontology

disease pathway


Label Type Compact URI Comment
DHET Metabolite chebi:64005
EET Metabolite chebi:64007
VLDL Metabolite chebi:39027
Cholesterol Metabolite chebi:16113
HDL Metabolite chebi:47775
LDL Metabolite chebi:47774
Lipoprotein Metabolite chebi:6495
IDL Metabolite chebi:132933
Cholesterol Metabolite chebi:16113
Triglyceride Metabolite chebi:17855
Phospholipid Metabolite chebi:16247
USF1 GeneProduct ensembl:ENSG00000158773
EPHX2 GeneProduct ensembl:ENSG00000120915
GHR GeneProduct ensembl:ENSG00000112964
PCSK9 GeneProduct ensembl:ENSG00000169174
LDLRAP1 GeneProduct ensembl:ENSG00000157978
APOB GeneProduct ensembl:ENSG00000084674
APOA2 GeneProduct ensembl:ENSG00000158874
APOA4 GeneProduct ensembl:ENSG00000110244
LIPC GeneProduct ensembl:ENSG00000166035
APOA1 GeneProduct ensembl:ENSG00000118137
LCAT GeneProduct ensembl:ENSG00000213398
LDLR GeneProduct ensembl:ENSG00000130164
PLTP GeneProduct ensembl:ENSG00000100979
LPL GeneProduct ensembl:ENSG00000175445
GPIHBP1 GeneProduct ensembl:ENSG00000277494
GPIHBP1 GeneProduct ensembl:ENSG00000277494
LPL GeneProduct ensembl:ENSG00000175445
CETP GeneProduct ensembl:ENSG00000087237
CETP GeneProduct ensembl:ENSG00000087237
CETP GeneProduct ensembl:ENSG00000087237


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