Familial hyperlipidemia type 1 (WP5108)

Homo sapiens

Familial hyperlipidemias are classified according to the Fredrickson classification. Type 1 of this classification is linked to a decrease of LPL, either through mutations on the gene itself or because of other factors. LPL hydrolyzed triglycerides in chylomicrons and in very low-density lipoproteins. Type 1 familial hyperlipidemia shows an increase of chylomicrons. LPL normally hydrolizes these chylomicrons into chylomicron remnants. However, mutations in LPL have been shown to be the cause of the first form of type 1 hyperlipidemia. In tissue, LMF1 causes proper folding and assembly of LPL, which is stabalized by Sel1L. LPL is then transported to the endothelial cell surface of the capillary lumen, where it binds to GPIHBP1. APOC2 is essential for LPL activation, which is stabalized by APOA5. Studies have found another form of LPL activity, but with an increased amount of LPL inhibitors. These inhibitors are ANGPTL3,4 and 8. Which of these are inhibiting LPL depends on the tissue the LPL is in.


Ulas Babayigit and Friederike Ehrhart


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Homo sapiens


Rare Diseases


Disease Ontology

familial GPIHBP1 deficiency familial lipase maturation factor 1 deficiency familial chylomicronemia due to inhibition of lipoprotein lipase activity familial lipoprotein lipase deficiency familial apolipoprotein C-II deficiency familial hyperlipidemia familial chylomicronemia syndrome

Pathway Ontology

disease pathway


Label Type Compact URI Comment
Chylomicron Metabolite wikidata:Q423126
Chylomicron remnant Metabolite wikidata:Q14890553
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
ANGPTL8 GeneProduct ensembl:ENSG00000130173
ANGPTL4 GeneProduct ensembl:ENSG00000167772
APOA2 GeneProduct ensembl:ENSG00000158874
LRP1 GeneProduct ensembl:ENSG00000123384
APOA4 GeneProduct ensembl:ENSG00000110244
CETP GeneProduct ensembl:ENSG00000087237
LIPC GeneProduct ensembl:ENSG00000166035
APOA1 GeneProduct ensembl:ENSG00000118137
LCAT GeneProduct ensembl:ENSG00000213398
LDLR GeneProduct ensembl:ENSG00000130164
PLTP GeneProduct ensembl:ENSG00000100979
GPIHBP1 GeneProduct ensembl:ENSG00000277494
LPL GeneProduct ensembl:ENSG00000175445
ANGPTL3 GeneProduct ensembl:ENSG00000132855
APOC2 GeneProduct ensembl:ENSG00000234906
APOA5 GeneProduct ensembl:ENSG00000110243
CETP GeneProduct ensembl:ENSG00000087237
CETP GeneProduct ensembl:ENSG00000087237
LPL GeneProduct ensembl:ENSG00000175445
LPL GeneProduct ensembl:ENSG00000175445
GPIHBP1 GeneProduct ensembl:ENSG00000277494
SEL1L GeneProduct ensembl:ENSG00000071537
LMF1 GeneProduct ensembl:ENSG00000103227


  1. Familial Lipoprotein Lipase Deficiency. Burnett JR, Hooper AJ, Hegele RA. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1999. PubMed Europe PMC Scholia
  2. Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis. Go GW, Mani A. Yale J Biol Med. 2012 Mar;85(1):19–28. PubMed Europe PMC Scholia
  3. Cholesteryl ester transfer protein inhibitors for dyslipidemia: focus on dalcetrapib. Goldberg AS, Hegele RA. Drug Des Devel Ther. 2012;6:251–9. PubMed Europe PMC Scholia
  4. Association of CETP and LIPC Gene Polymorphisms with HDL and LDL Sub-fraction Levels in a Group of Indian Subjects: A Cross-Sectional Study. Todur SP, Ashavaid TF. Indian J Clin Biochem. 2013 Apr;28(2):116–23. PubMed Europe PMC Scholia
  5. Targeting APOC3 in the familial chylomicronemia syndrome. Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, et al. N Engl J Med. 2014 Dec 4;371(23):2200–6. PubMed Europe PMC Scholia
  6. Introduction to Lipids and Lipoproteins. Feingold KR. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2021. PubMed Europe PMC Scholia
  7. High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol. Tosheska Trajkovska K, Topuzovska S. Anatol J Cardiol. 2017 Aug;18(2):149–54. PubMed Europe PMC Scholia
  8. Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism. Wolska A, Dunbar RL, Freeman LA, Ueda M, Amar MJ, Sviridov DO, et al. Atherosclerosis. 2017 Dec;267:49–60. PubMed Europe PMC Scholia
  9. N-terminal mutation of apoA-I and interaction with ABCA1 reveal mechanisms of nascent HDL biogenesis. Liu M, Mei X, Herscovitz H, Atkinson D. J Lipid Res. 2019 Jan;60(1):44–57. PubMed Europe PMC Scholia
  10. Genetic and secondary causes of severe HDL deficiency and cardiovascular disease. Geller AS, Polisecki EY, Diffenderfer MR, Asztalos BF, Karathanasis SK, Hegele RA, et al. J Lipid Res. 2018 Dec;59(12):2421–35. PubMed Europe PMC Scholia
  11. Identification of ApoA4 as a sphingosine 1-phosphate chaperone in ApoM- and albumin-deficient mice. Obinata H, Kuo A, Wada Y, Swendeman S, Liu CH, Blaho VA, et al. J Lipid Res. 2019 Nov;60(11):1912–21. PubMed Europe PMC Scholia
  12. Interleukin 10 promotes macrophage uptake of HDL and LDL by stimulating fluid-phase endocytosis. Lucero D, Islam P, Freeman LA, Jin X, Pryor M, Tang J, et al. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Feb;1865(2):158537. PubMed Europe PMC Scholia
  13. Association between the APOA2 rs3813627 Single Nucleotide Polymorphism and HDL and APOA1 Levels Through BMI. Boughanem H, Bandera-Merchán B, Hernández-Alonso P, Moreno-Morales N, Tinahones FJ, Lozano J, et al. Biomedicines. 2020 Feb 27;8(3):44. PubMed Europe PMC Scholia
  14. Remnants of the Triglyceride-Rich Lipoproteins, Diabetes, and Cardiovascular Disease. Chait A, Ginsberg HN, Vaisar T, Heinecke JW, Goldberg IJ, Bornfeldt KE. Diabetes. 2020 Apr;69(4):508–16. PubMed Europe PMC Scholia