Familial hyperlipidemia type 2 (Homo sapiens)

From WikiPathways

Jump to: navigation, search
ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none Type II BCellular transcriptionfactorMutation leadingto differentphenotypeLipid signalingFHCL1FHCL4FCHL2FCHL1FHCL3HYPLIP2FCHL3USF1DHETFamilial combined hyperlipidemiaEETFamilialhypercholesterolemiaFamilialhyperlipidemiaType II AEPHX2GHRPCSK9LDLRAP1APOBHepatocyteVLDLAPOA2APOA4APOA1PLTPCholesterolHDLLDLLipoproteinIDLLIPCLCATLDLRLPLGPIHBP1GPIHBP1LPLCETPxTransportBindingInhibitionConversionGene/proteinMetaboliteCatalysisStimulationMutationsLegendxCETPCETPCholesterolTriglyceridePhospholipidName: Familial hyperlipidemia type 2Organism: Homo sapiens


Description

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.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Image:Curated.pngApproved version
Image:Wplogo_31.pngCommunity: Rare Diseases

Ontology Terms

Cell Type : osteoblast
 

Bibliography

View all...
  1. Feingold KR; ''Introduction to Lipids and Lipoproteins''; , 2000 PubMed Europe PMC Scholia
  2. Goldberg AS, Hegele RA; ''Cholesteryl ester transfer protein inhibitors for dyslipidemia: focus on dalcetrapib.''; Drug Des Devel Ther, 2012 PubMed Europe PMC Scholia
  3. Edin ML, Hamedani BG, Gruzdev A, Graves JP, Lih FB, Arbes SJ 3rd, Singh R, Orjuela Leon AC, Bradbury JA, DeGraff LM, Hoopes SL, Arand M, Zeldin DC; ''Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia.''; J Biol Chem, 2018 PubMed Europe PMC Scholia
  4. Lucero D, Islam P, Freeman LA, Jin X, Pryor M, Tang J, Kruth HS, Remaley AT; ''Interleukin 10 promotes macrophage uptake of HDL and LDL by stimulating fluid-phase endocytosis.''; Biochim Biophys Acta Mol Cell Biol Lipids, 2020 PubMed Europe PMC Scholia
  5. Sato K, Emi M, Ezura Y, Fujita Y, Takada D, Ishigami T, Umemura S, Xin Y, Wu LL, Larrinaga-Shum S, Stephenson SH, Hunt SC, Hopkins PN; ''Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred.''; J Hum Genet, 2004 PubMed Europe PMC Scholia
  6. Lagace TA; ''PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells.''; Curr Opin Lipidol, 2014 PubMed Europe PMC Scholia
  7. Youngblom E, Pariani M, Knowles JW; ''Familial Hypercholesterolemia''; , 1993 PubMed Europe PMC Scholia
  8. Geller AS, Polisecki EY, Diffenderfer MR, Asztalos BF, Karathanasis SK, Hegele RA, Schaefer EJ; ''Genetic and secondary causes of severe HDL deficiency and cardiovascular disease.''; J Lipid Res, 2018 PubMed Europe PMC Scholia
  9. Ayhan H, Gormus U, Isbir S, Yilmaz SG, Isbir T; ''SCARB1Gene Polymorphisms and HDL Subfractions in Coronary Artery Disease.''; In Vivo, 2017 PubMed Europe PMC Scholia
  10. Liu M, Mei X, Herscovitz H, Atkinson D; ''N-terminal mutation of apoA-I and interaction with ABCA1 reveal mechanisms of nascent HDL biogenesis.''; J Lipid Res, 2019 PubMed Europe PMC Scholia
  11. Takada D, Emi M, Ezura Y, Nobe Y, Kawamura K, Iino Y, Katayama Y, Xin Y, Wu LL, Larringa-Shum S, Stephenson SH, Hunt SC, Hopkins PN; ''Interaction between the LDL-receptor gene bearing a novel mutation and a variant in the apolipoprotein A-II promoter: molecular study in a 1135-member familial hypercholesterolemia kindred.''; J Hum Genet, 2002 PubMed Europe PMC Scholia
  12. Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, Geary RS, Baker BF, Graham MJ, Crooke RM, Witztum JL; ''Targeting APOC3 in the familial chylomicronemia syndrome.''; N Engl J Med, 2014 PubMed Europe PMC Scholia
  13. Pajukanta P, Nuotio I, Terwilliger JD, Porkka KV, Ylitalo K, Pihlajamäki J, Suomalainen AJ, Syvänen AC, Lehtimäki T, Viikari JS, Laakso M, Taskinen MR, Ehnholm C, Peltonen L; ''Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23.''; Nat Genet, 1998 PubMed Europe PMC Scholia
  14. Wood MA, Walker WH; ''USF1/2 transcription factor DNA-binding activity is induced during rat Sertoli cell differentiation.''; Biol Reprod, 2009 PubMed Europe PMC Scholia
  15. Tosheska Trajkovska K, Topuzovska S; ''High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol.''; Anatol J Cardiol, 2017 PubMed Europe PMC Scholia
  16. Obinata H, Kuo A, Wada Y, Swendeman S, Liu CH, Blaho VA, Nagumo R, Satoh K, Izumi T, Hla T; ''Identification of ApoA4 as a sphingosine 1-phosphate chaperone in ApoM- and albumin-deficient mice.''; J Lipid Res, 2019 PubMed Europe PMC Scholia
  17. Takada D, Ezura Y, Ono S, Iino Y, Katayama Y, Xin Y, Wu LL, Larringa-Shum S, Stephenson SH, Hunt SC, Hopkins PN, Emi M; ''Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred.''; Am J Med Genet A, 2003 PubMed Europe PMC Scholia
  18. Bello-Chavolla OY, Kuri-García A, Ríos-Ríos M, Vargas-Vázquez A, Cortés-Arroyo JE, Tapia-González G, Cruz-Bautista I, Aguilar-Salinas CA; ''FAMILIAL COMBINED HYPERLIPIDEMIA: CURRENT KNOWLEDGE, PERSPECTIVES, AND CONTROVERSIES.''; Rev Invest Clin, 2018 PubMed Europe PMC Scholia
  19. Rhainds D, Brissette L; ''The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders.''; Int J Biochem Cell Biol, 2004 PubMed Europe PMC Scholia
  20. Morita SY; ''Metabolism and Modification of Apolipoprotein B-Containing Lipoproteins Involved in Dyslipidemia and Atherosclerosis.''; Biol Pharm Bull, 2016 PubMed Europe PMC Scholia
  21. Todur SP, Ashavaid TF; ''Association of CETP and LIPC Gene Polymorphisms with HDL and LDL Sub-fraction Levels in a Group of Indian Subjects: A Cross-Sectional Study.''; Indian J Clin Biochem, 2013 PubMed Europe PMC Scholia
  22. Boughanem H, Bandera-Merchán B, Hernández-Alonso P, Moreno-Morales N, Tinahones FJ, Lozano J, Morcillo S, Macias-Gonzalez M; ''Association between theAPOA2rs3813627 Single Nucleotide Polymorphism and HDL and APOA1 Levels Through BMI.''; Biomedicines, 2020 PubMed Europe PMC Scholia
  23. Go GW, Mani A; ''Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis.''; Yale J Biol Med, 2012 PubMed Europe PMC Scholia
  24. Huang A, Sun D; ''Sexually Dimorphic Regulation of EET Synthesis and Metabolism: Roles of Estrogen.''; Front Pharmacol, 2018 PubMed Europe PMC Scholia
  25. ''''; , PubMed Europe PMC Scholia
  26. Wolska A, Dunbar RL, Freeman LA, Ueda M, Amar MJ, Sviridov DO, Remaley AT; ''Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism.''; Atherosclerosis, 2017 PubMed Europe PMC Scholia
  27. Burnett JR, Hooper AJ, Hegele RA; ''Familial Lipoprotein Lipase Deficiency''; , 1993 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
136858
Approved
view01:20, 25 February 2025EweitzModified description
136857view01:01, 25 February 2025EweitzStack nodes
136856view00:56, 25 February 2025EweitzModified description
136557
RARE
view18:44, 7 February 2025EweitzRefine interaction positions
136556view18:38, 7 February 2025EweitzRefine legend text alignment
136555view18:35, 7 February 2025EweitzRefine interaction positions
136554view18:34, 7 February 2025EweitzEconomize layout
136553view18:32, 7 February 2025EweitzRefine node alignment
136552view18:28, 7 February 2025EweitzRefine cell type label, economize layout
136551view18:25, 7 February 2025EweitzEconomize layout
135230view21:57, 8 August 2024EweitzClear cache to update board dimensions
135229view21:56, 8 August 2024EweitzEconomize layout
135228view12:36, 8 August 2024EweitzAlign anchor
135227view12:35, 8 August 2024EweitzAlign nodes
135226view12:34, 8 August 2024EweitzEconomize layout
135225view12:26, 8 August 2024EweitzRefine legend, economize layout
135224view12:02, 8 August 2024EweitzRefine legend
135223view12:01, 8 August 2024EweitzEconomize layout
135222view11:57, 8 August 2024EweitzEconomize layout
134579view23:43, 22 July 2024EweitzOntology Term : 'hepatocyte' added !
134373view13:29, 21 July 2024EgonwRemoved template comments
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

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
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 hypercholesterolemiaQ2711291 (Wikidata)
Familial hyperlipidemiaQ18554145 (Wikidata)
Familial combined hyperlipidemiaQ2242370 (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

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5109"
Personal tools