Familial hyperlipidemia type 2 (Homo sapiens)

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82523625Cellular transcriptionfactorLipid signalingType II BMutation leadingto differentphenotypeDHETFCHL2FHCL4USF1HYPLIP2FCHL3FHCL3FCHL1FHCL14132082119Familial combined hyperlipidemiaEETFamilial hypercholesterolemiaFamilial hyperlipidemia20, 232Type II AEPHX2GHRPCSK9LDLRAP1APOB20, 2326262618Liver245, 7, 1822, 24, 2752414, 15, 24, 275151, 1757VLDLAPOA2CholesterolHDLLDLAPOA4LipoproteinIDLLIPCAPOA1LCATLDLRPLTPLPLGPIHBP1GPIHBP1LPLCETP720, 2320, 2316xTransportBindingInhibitionConversionGene/proteinMetaboliteCatalysisStimulationMutationsLegendx55CETP75, 7, 18CETP718CholesterolTriglyceridePhospholipid


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.

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120391view08:42, 30 November 2021Fehrhartfixed weird characters in literature list
119149view10:52, 18 June 2021UlasBabayigitCorrected transport arrows and added comment
119148view10:50, 18 June 2021UlasBabayigitCorrected arrows into graphical lines.
119147view10:48, 18 June 2021UlasBabayigitCorrected arrows into graphical lines.
119146view10:47, 18 June 2021UlasBabayigitCorrected arrows into graphical lines.
118696view07:31, 1 June 2021UlasBabayigitOntology Term : 'disease pathway' added !
118671view06:54, 1 June 2021UlasBabayigitAdded wikidata link to FCHL3 node.
118503view09:13, 28 May 2021UlasBabayigitOntology Term : 'familial hyperlipidemia' added !
118489view08:29, 28 May 2021UlasBabayigitOntology Term : 'familial combined hyperlipidemia' added !
118488view08:28, 28 May 2021UlasBabayigitOntology Term : 'familial hypercholesterolemia' added !
118487view08:27, 28 May 2021UlasBabayigitNew pathway

External references


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NameTypeDatabase referenceComment
APOA1GeneProductENSG00000118137 (Ensembl)
APOA2GeneProductENSG00000158874 (Ensembl)
APOA4GeneProductENSG00000110244 (Ensembl)
APOBGeneProductENSG00000084674 (Ensembl)
CETPGeneProductENSG00000087237 (Ensembl)
CholesterolMetaboliteCHEBI:16113 (ChEBI)
DHETMetaboliteCHEBI:64005 (ChEBI)
EETMetaboliteCHEBI:64007 (ChEBI)
EPHX2GeneProductENSG00000120915 (Ensembl)
FCHL1Q18032304 (Wikidata)
FCHL2Q14890615 (Wikidata)
FCHL3Q2242370 (Wikidata) Unclear what this subtypes is seperated on compared to the main class of combined hyperlipidemia. Wikidata is shared for both.
FHCL1Q14872724 (Wikidata)
FHCL3Q3359612 (Wikidata)
FHCL4Q18038122 (Wikidata)
Familial combined hyperlipidemiaQ2242370 (Wikidata)
Familial hypercholesterolemiaQ2711291 (Wikidata)
Familial hyperlipidemiaQ18554145 (Wikidata)
GHRGeneProductENSG00000112964 (Ensembl)
GPIHBP1GeneProductENSG00000277494 (Ensembl)
HDLMetaboliteCHEBI:47775 (ChEBI)
HYPLIP2Q20772119 (Wikidata)
IDLMetaboliteCHEBI:132933 (ChEBI)
LCATGeneProductENSG00000213398 (Ensembl)
LDLMetaboliteCHEBI:47774 (ChEBI)
LDLRAP1GeneProductENSG00000157978 (Ensembl)
LDLRGeneProductENSG00000130164 (Ensembl)
LIPCGeneProductENSG00000166035 (Ensembl)
LPLGeneProductENSG00000175445 (Ensembl)
LipoproteinMetaboliteCHEBI:6495 (ChEBI)
PCSK9GeneProductENSG00000169174 (Ensembl)
PLTPGeneProductENSG00000100979 (Ensembl)
PhospholipidMetaboliteCHEBI:16247 (ChEBI)
TriglycerideMetaboliteCHEBI:17855 (ChEBI)
USF1GeneProductENSG00000158773 (Ensembl)
VLDLMetaboliteCHEBI:39027 (ChEBI)

Annotated Interactions

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