LPL Gene: Lipoprotein Lipase - Function, Mutations, and Associated Diseases
A comprehensive biomedical overview of the LPL gene, including its genomic context, protein function, tissue expression, disease associations, and clinical significance.
Gene Information Card
| Symbol | LPL |
|---|---|
| Full Name | Lipoprotein Lipase |
| Gene Type | Protein coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 4023 ncbi.nlm.nih.gov/gene/4023 |
| Ensembl ID | ENSG00000175445 |
| UniProt ID | P06858 |
| OMIM ID | 609708 |
| HGNC ID | 6677 |
| Aliases | LIPD, Lipase, Lipoprotein, Lipoprotein Lipase (LPL) |
Description
The LPL gene encodes lipoprotein lipase, a rate-limiting enzyme in the hydrolysis of triglycerides from circulating chylomicrons and very low-density lipoproteins (VLDL). This enzyme is primarily expressed in adipose tissue, skeletal muscle, and cardiac muscle, where it facilitates the release of free fatty acids for energy production or storage. Defects in the LPL gene are the primary cause of familial chylomicronemia syndrome (Type I hyperlipoproteinemia), characterized by severe hypertriglyceridemia and recurrent pancreatitis. The protein functions as a homodimer and requires glycosylation and the cofactor apolipoprotein C-II for optimal activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial Chylomicronemia Syndrome (FCS) | Loss-of-function mutations in LPL lead to a deficiency or absence of functional lipoprotein lipase, preventing the hydrolysis of triglycerides in chylomicrons and VLDL. This results in massive accumulation of chylomicrons in plasma. | ClinVar, OMIM |
| Hyperlipoproteinemia, Type I | This is a synonym for familial chylomicronemia syndrome, caused by homozygous or compound heterozygous mutations in the LPL gene, leading to severe hypertriglyceridemia. | OMIM, NCBI |
| Lipoprotein Lipase Deficiency | A direct consequence of LPL gene mutations, resulting in reduced or absent enzyme activity, leading to impaired triglyceride clearance. | ClinVar, OMIM |
| Hypertriglyceridemia, Susceptibility to | Certain heterozygous mutations or common polymorphisms in LPL can increase susceptibility to hypertriglyceridemia, especially when combined with other genetic or environmental factors. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose Tissue | High | High |
| Skeletal Muscle | High | High |
| Heart Muscle | High | High |
| Mammary Gland | Medium | Medium |
| Lung | Low | Low |
| Kidney | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Adipocytes | High | Primary site of LPL expression and function. |
| Skeletal Muscle Cells | High | Expression is regulated by nutritional and hormonal signals. |
| Cardiomyocytes | High | Important for cardiac energy supply. |
| Macrophages | Low | Expression can be induced in atherosclerotic plaques. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.835C>T (p.Arg279Ter) | Nonsense | Rare | Premature stop codon leading to a truncated, non-functional protein. Associated with severe LPL deficiency. |
| c.983C>T (p.Pro328Leu) | Missense | Rare | Disrupts protein folding and dimerization, leading to loss of enzymatic activity. |
| c.1063G>A (p.Asp355Asn) | Missense | Rare | Affects catalytic activity, reducing the enzyme's ability to hydrolyze triglycerides. |
| c.953A>G (p.Asn318Ser) | Missense | Common polymorphism | Associated with increased risk of hypertriglyceridemia and cardiovascular disease, but with variable penetrance. |
Mutation functional classification
Loss of Function (LOF)
The majority of disease-causing LPL mutations are loss-of-function. These mutations lead to reduced or absent enzyme activity, impairing triglyceride hydrolysis and causing severe hypertriglyceridemia.
Gain of Function (GOF)
No clinically significant gain-of-function mutations have been described for LPL.
Dominant Negative (DN)
While LPL functions as a homodimer, most pathogenic mutations are recessive. However, some missense mutations may exert a dominant-negative effect by forming inactive heterodimers with the wild-type protein, though this is not the primary mechanism for most cases.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004465 (GO:0004465) | • GO:0008201 (GO:0008201) |
| • GO:0016787 (GO:0016787) | • GO:0005615 (GO:0005615) |
| • GO:0005886 (GO:0005886) | • GO:0006641 (GO:0006641) |
| • GO:0019433 (GO:0019433) | • GO:0033344 (GO:0033344) |
| • GO:0051006 (GO:0051006) |
Pathways
• Triglyceride Metabolism
• Lipoprotein Metabolism
• PPAR Signaling Pathway
• Fatty Acid Degradation
Protein Summary
Lipoprotein lipase (LPL) is a secreted glycoprotein that functions as a homodimer. It is the principal enzyme responsible for the hydrolysis of triglycerides in plasma lipoproteins, primarily chylomicrons and very low-density lipoproteins (VLDL). The enzyme is anchored to the luminal surface of capillary endothelial cells via glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). LPL activity is crucial for providing free fatty acids to peripheral tissues for energy production or storage. Its activity is regulated by nutritional status, hormones, and the cofactor apolipoprotein C-II. Deficiency or dysfunction of LPL leads to severe hypertriglyceridemia and associated clinical complications.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LPL Knockout HEK293 Cell Line | EDJ-KQ5140 | Human | 4023 | Details Get a Quote |
| LPL Knockout HeLa Cell Line | EDJ-KQ28102 | Human | 4023 | Details Get a Quote |
| LPL Knockout A-549 Cell Line | EDJ-KQ62283 | Human | 4023 | Details Get a Quote |
| LPL Knockout HCT 116 Cell Line | EDJ-KQ70764 | Human | 4023 | Details Get a Quote |
