Pancreatic, hepatic and gastric/lingual lipase are closely related to each other and to lipoprotein lipase (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL). Familial human hepatic lipase deficiency is a rare recessive disorder Two variants (S267F and T383M) are rare mutations found to date only in HL deficient subjects and their relatives. Of the six HL variants described to date, only S267F and T383M are associated with hyperlipidemia. human-LIPC. The disease is characterised by premature atherosclerosis and abnormal circulating lipoproteins
Hepatic lipase (gene: LIPC; enzyme: HL; E.C.3.1.1.3) is one of three members of the triglyceride lipase family that contributes to vascular lipoprotein degradation and serves a dual role in triglyceride hydrolysis and in facilitating receptor-mediated lipoprotein uptake into the liver. Amino acid sequences, protein structures, and gene locations for vertebrate LIPC (or Lipc for mouse and rat) genes and proteins were sourced from previous reports and vertebrate genome databases. Lipc was distinct from other neutral lipase genes (Lipg encoding endothelial lipase and Lpl encoding lipoprotein lipase [LPL]) and was located on mouse chromosome 9 with nine coding exons on the negative strand. Exon 9 of human LIPC and mouse and rat Lipc genes contained "stop codons" in different positions, causing changes in C-termini length. Vertebrate HL protein subunits shared 58%-97% sequence identities, including active, signal peptide, disulfide bond, and N-glycosylation sites, as well as proprotein convertase ("hinge") and heparin binding regions. Predicted secondary and tertiary structures revealed similarities with the three-dimensional structure reported for horse and human pancreatic lipases. Potential sites for regulating LIPC gene expression included CpG islands near the 5''-untranslated regions of the mouse and rat LIPC genes. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate LIPC gene family with other neutral triglyceride lipase gene families (LIPG and LPL). We conclude that the triglyceride lipase ancestral gene for vertebrate neutral lipase genes (LIPC, LIPG, and LPL) predated the appearance of fish during vertebrate evolution.
        
Title: Human hepatic lipase mutations and polymorphisms Hegele RA, Tu L, Connelly PW Ref: Hum Mutat, 1:320, 1992 : PubMed
Human hepatic lipase (HL) is a 477 residue glycoprotein that hydrolyzes triglycerides from plasma lipoproteins. Familial HL deficiency is a rare recessive disorder that is characterized by premature atherosclerosis and abnormal circulating lipoproteins. While studying the HL gene from the world's index family with HL deficiency, we identified four coding sequence variants of HL, one in each of exons 4, 5, 6, and 8. In this report we present the genetic basis for two new HL gene variants, one in each of exons 3 and 5. All six HL DNA variants are single base pair changes. Two variants (at codons 133 and 202) are diallelic DNA polymorphisms that are silent at the amino acid level. One variant (V73M) is an allele that defines an uncommon HL isoprotein. One variant (N193S) has two alleles of approximately equal frequency in the population that specify two common HL isoproteins. Two variants (S267F and T383M) are rare mutations found to date only in HL deficient subjects and their relatives. Of the six HL variants described to date, only S267F and T383M are associated with hyperlipidemia.