ANGPTL3

The protein encoded by this gene is a member of the angiopoietin-like family of secreted factors. It is expressed predominantly in the liver, and has the characteristic structure of angiopoietins, consisting of a signal peptide, N-terminal coiled-coil domain, and the C-terminal fibrinogen (FBN)-like domain. The FBN-like domain in angiopoietin-like 3 protein was shown to bind alpha-5/beta-3 integrins, and this binding induced endothelial cell adhesion and migration. This protein may also play a role in the regulation of angiogenesis.

Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL),{{cite journal | vauthors = Tikka A, Jauhiainen M | title = The role of ANGPTL3 in controlling lipoprotein metabolism | journal = Endocrine | volume = 52 | issue = 2 | pages = 187–93 | date = May 2016 | pmid = 26754661 | pmc = 4824806 | doi = 10.1007/s12020-015-0838-9 }} thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans.

ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels.{{citation needed|date=March 2018}} Circulating PL-rich HDL particles have high cholesterol efflux abilities.{{citation needed|date=March 2018}}

Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state,{{cite journal | vauthors = Wang Y, McNutt MC, Banfi S, Levin MG, Holland WL, Gusarova V, Gromada J, Cohen JC, Hobbs HH | display-authors = 6 | title = Hepatic ANGPTL3 regulates adipose tissue energy homeostasis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 37 | pages = 11630–5 | date = September 2015 | pmid = 26305978 | pmc = 4577179 | doi = 10.1073/pnas.1515374112 | bibcode = 2015PNAS..11211630W | doi-access = free }} likely through activation by Angptl8, a feeding-induced hepatokine,{{cite journal | vauthors = Zhang R | title = Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels | journal = Biochemical and Biophysical Research Communications | volume = 424 | issue = 4 | pages = 786–92 | date = August 2012 | pmid = 22809513 | doi = 10.1016/j.bbrc.2012.07.038 }}{{cite journal | vauthors = Ren G, Kim JY, Smas CM | title = Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 303 | issue = 3 | pages = E334-51 | date = August 2012 | pmid = 22569073 | pmc = 3423120 | doi = 10.1152/ajpendo.00084.2012 }} to inhibit postprandial LPL activity in cardiac and skeletal muscles,{{cite journal | vauthors = Fu Z, Abou-Samra AB, Zhang R | title = A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase | journal = Scientific Reports | volume = 5 | pages = 18502 | date = December 2015 | pmid = 26687026 | pmc = 4685196 | doi = 10.1038/srep18502 | bibcode = 2015NatSR...518502F }} as suggested by the ANGPTL3-4-8 model.{{cite journal | vauthors = Zhang R | title = The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking | journal = Open Biology | volume = 6 | issue = 4 | pages = 150272 | date = April 2016 | pmid = 27053679 | pmc = 4852456 | doi = 10.1098/rsob.150272 | url = http://rsob.royalsocietypublishing.org/content/6/4/150272.long | access-date = 2016-04-15 | url-status = dead | archive-url = https://web.archive.org/web/20180804201514/http://rsob.royalsocietypublishing.org/content/6/4/150272.long | archive-date = 2018-08-04 }}

In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.{{cn|date=June 2021}}

In humans with genetic loss-of-function variants in one copy of ANGPTL3, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").{{cite journal | vauthors = Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E, Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert JC, DePristo MA, Daly MJ, Cohen JC, Hobbs HH, Altshuler D, Schonfeld G, Gabriel SB, Yue P, Kathiresan S | display-authors = 6 | title = Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia | journal = The New England Journal of Medicine | volume = 363 | issue = 23 | pages = 2220–7 | date = December 2010 | pmid = 20942659 | pmc = 3008575 | doi = 10.1056/NEJMoa1002926 }}

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• {{UCSC gene info|ANGPTL3}}
• {{PDBe-KB2|Q9Y5C1|Angiopoietin-related protein 3}}