LPL
lipoprotein lipase, the group of Lipases
Basic information
Region (hg38): 8:19901716-19967259
Previous symbols: [ "LIPD" ]
Links
Phenotypes
GenCC
Source:
- hyperlipidemia, familial combined, LPL related (Strong), mode of inheritance: AD
- familial lipoprotein lipase deficiency (Strong), mode of inheritance: AR
- familial lipoprotein lipase deficiency (Definitive), mode of inheritance: AR
- familial lipoprotein lipase deficiency (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hyperlipidemia, familial combined, 3; Lipoprotein lipase deficiency | AD/AR | Cardiovascular; Gastrointestinal; Pharmacogenomic | Patients with Hyperlipidemia, familial combinedL are at increased risk of cardiovascular disease, as well as other comorbid conditions, and awareness may allow early medical and lifestyle management to prevent sequelae; In LPL deficiency, treatment centers on medical (eg, inhibitors of APOC3 mRNA have been reported as beneficial related to lower triglyceride measurements) and nutrition therapy (eg, reducing fat intake, alcohol abstinence, as well as antioxidant therapy related to risks of sequelae) aimed to maintain plasma triglyceride concentration less than 1000 mg/dL; In LPL deficiency, gene therapy (Alipogene tiparvovec) is clinically available; Treatment of acute pancreatitis involves fasting with low-calorie infusion; Medical treatment (eg, with fibrates) may be beneficial in adults with LPL deficiency; Certain medications that can affect triglyceride levels should be avoided, and sequelae such as pancreatitis may be precipitated by OCPs | Cardiovascular; Gastrointestinal; Hematologic | 13483896; 13712364; 3630977; 4719678; 6638056; 6645961; 2648155; 2536938; 2110364; 2294743; 1969408; 2121025; 1975597; 2394828; 2010533; 1702428; 1907278; 1752947; 1674945; 2038366; 1530621; 1562620; 1400331; 1598907; 1511985; 1639392; 1512512; 1731801; 1737848; 8096693; 8486765; 8325986; 7906986; 8541837; 7753827; 8755931; 8778602; 9401010; 9738727; 10517255; 10199753; 11134145; 11334614; 15928243; 16174715; 15840743; 16552344; 17032721; 19295657; 20301485; 21159338; 22129523; 22239554; 22438229; 22717743; 23527320; 24142281; 25470695; 30307446 |
| Heterozygous variants can contribute to Familial combined hyperlipidemia (LPL deficiency is an autosomal recessive disorder) |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (429 variants)
- Hyperlipoproteinemia, type I (168 variants)
- Cardiovascular phenotype (150 variants)
- not specified (44 variants)
- Hyperlipidemia, familial combined, LPL related (25 variants)
- Inborn genetic diseases (18 variants)
- Hyperlipoproteinemia, type I;Hyperlipidemia, familial combined, LPL related (10 variants)
- Hyperlipidemia, familial combined, LPL related;Hyperlipoproteinemia, type I (7 variants)
- LPL-related condition (2 variants)
- High density lipoprotein cholesterol level quantitative trait locus 11 (2 variants)
- Hyperlipidemia, familial combined, susceptibility to (2 variants)
- Dystrophin deficiency (2 variants)
- LIPOPROTEIN LIPASE POLYMORPHISM (1 variants)
- LIPOPROTEIN LIPASE (OLBIA) (1 variants)
- Coronary heart disease (1 variants)
- Hypertriglyceridemia (1 variants)
- Dilated cardiomyopathy 1A (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LPL gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 181 | 185 | ||||
| missense | 12 | 28 | 107 | 153 | ||
| nonsense | 16 | 23 | ||||
| start loss | 1 | |||||
| frameshift | 19 | 21 | ||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 9 | |||||
| splice region ? | 2 | 1 | 3 | 28 | 34 | |
| non coding ? | 51 | 50 | 46 | 147 | ||
| Total | 52 | 39 | 161 | 236 | 52 |
Highest pathogenic variant AF is 0.0000657
Variants in LPL
This is a list of pathogenic ClinVar variants found in the LPL region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-19939142-T-G | Hyperlipoproteinemia, type I | Uncertain significance (Jun 14, 2016) | ||
| 8-19939158-G-T | Hyperlipoproteinemia, type I | Conflicting classifications of pathogenicity (May 04, 2019) | ||
| 8-19939160-T-G | Hyperlipoproteinemia, type I • Hyperlipidemia, familial combined, susceptibility to | Benign (Dec 18, 2023) | ||
| 8-19939200-G-C | not specified • LPL-related disorder | Conflicting classifications of pathogenicity (Nov 20, 2023) | ||
| 8-19939214-T-C | Hyperlipidemia, familial combined, susceptibility to | risk factor (May 09, 1995) | ||
| 8-19939265-T-TCC | Hyperlipoproteinemia, type I | Conflicting classifications of pathogenicity (Sep 21, 2023) | ||
| 8-19939305-T-C | Hyperlipoproteinemia, type I | Uncertain significance (Jan 13, 2018) | ||
| 8-19939340-C-T | Hyperlipoproteinemia, type I | Uncertain significance (Jan 13, 2018) | ||
| 8-19939370-C-G | Hyperlipoproteinemia, type I | Uncertain significance (Jan 13, 2018) | ||
| 8-19939392-C-T | Hyperlipoproteinemia, type I | Uncertain significance (Jan 13, 2018) | ||
| 8-19939403-C-G | Hyperlipoproteinemia, type I | Uncertain significance (Jan 12, 2018) | ||
| 8-19939438-G-T | Uncertain significance (Apr 20, 2022) | |||
| 8-19939443-G-A | Likely pathogenic (Jun 15, 2022) | |||
| 8-19939446-G-A | Likely benign (Mar 18, 2022) | |||
| 8-19939447-AGCAAAGCCCT-A | Pathogenic (Jun 13, 2021) | |||
| 8-19939448-G-A | not specified • Cardiovascular phenotype | Uncertain significance (Sep 13, 2022) | ||
| 8-19939449-C-T | Likely benign (Apr 01, 2021) | |||
| 8-19939455-C-A | Likely benign (Jan 26, 2024) | |||
| 8-19939455-C-G | Likely benign (Oct 04, 2023) | |||
| 8-19939455-C-T | Likely benign (Feb 22, 2019) | |||
| 8-19939458-G-T | Likely benign (Jan 20, 2023) | |||
| 8-19939461-C-A | Cardiovascular phenotype | Likely benign (Mar 18, 2022) | ||
| 8-19939471-C-T | Cardiovascular phenotype | Likely benign (May 24, 2022) | ||
| 8-19939473-G-A | Cardiovascular phenotype | Likely benign (Apr 26, 2021) | ||
| 8-19939473-G-T | Likely benign (May 18, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LPL | protein_coding | protein_coding | ENST00000311322 | 9 | 65542 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.27e-9 | 0.560 | 103778 | 1212 | 20758 | 125748 | 0.0915 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.503 | 283 | 260 | 1.09 | 0.0000143 | 3129 |
| Missense in Polyphen | 93 | 103.56 | 0.898 | 1253 | ||
| Synonymous | -2.08 | 127 | 101 | 1.26 | 0.00000608 | 897 |
| Loss of Function | 1.21 | 17 | 23.3 | 0.730 | 0.00000108 | 289 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.127 | 0.126 |
| Ashkenazi Jewish | 0.105 | 0.104 |
| East Asian | 0.113 | 0.112 |
| Finnish | 0.0882 | 0.0879 |
| European (Non-Finnish) | 0.102 | 0.101 |
| Middle Eastern | 0.113 | 0.112 |
| South Asian | 0.0965 | 0.0960 |
| Other | 0.0951 | 0.0954 |
dbNSFP
Source:
- Function
- FUNCTION: The primary function of this lipase is the hydrolysis of triglycerides of circulating chylomicrons and very low density lipoproteins (VLDL) (PubMed:27578112). Binding to heparin sulfate proteogylcans at the cell surface is vital to the function. The apolipoprotein, APOC2, acts as a coactivator of LPL activity in the presence of lipids on the luminal surface of vascular endothelium (By similarity). {ECO:0000250, ECO:0000269|PubMed:11342582, ECO:0000269|PubMed:27578112}.;
- Disease
- DISEASE: Lipoprotein lipase deficiency (LPL deficiency) [MIM:238600]: Recessive disorder usually manifesting in childhood. On a normal diet, patients often present with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive xanthomata, and massive hypertriglyceridemia, sometimes complicated with acute pancreatitis. {ECO:0000269|PubMed:10660334, ECO:0000269|PubMed:10787434, ECO:0000269|PubMed:11068186, ECO:0000269|PubMed:11099402, ECO:0000269|PubMed:11134145, ECO:0000269|PubMed:11441134, ECO:0000269|PubMed:12204001, ECO:0000269|PubMed:12641539, ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:1400331, ECO:0000269|PubMed:1479292, ECO:0000269|PubMed:14984478, ECO:0000269|PubMed:15185149, ECO:0000269|PubMed:1521525, ECO:0000269|PubMed:15256764, ECO:0000269|PubMed:15877202, ECO:0000269|PubMed:1598907, ECO:0000269|PubMed:1619366, ECO:0000269|PubMed:1639392, ECO:0000269|PubMed:1674945, ECO:0000269|PubMed:1702428, ECO:0000269|PubMed:1730727, ECO:0000269|PubMed:1752947, ECO:0000269|PubMed:1907278, ECO:0000269|PubMed:1969408, ECO:0000269|PubMed:1975597, ECO:0000269|PubMed:2010533, ECO:0000269|PubMed:2038366, ECO:0000269|PubMed:2110364, ECO:0000269|PubMed:2121025, ECO:0000269|PubMed:27578112, ECO:0000269|PubMed:7647785, ECO:0000269|PubMed:7806969, ECO:0000269|PubMed:7906986, ECO:0000269|PubMed:7912254, ECO:0000269|PubMed:7999071, ECO:0000269|PubMed:8077845, ECO:0000269|PubMed:8096693, ECO:0000269|PubMed:8135797, ECO:0000269|PubMed:8288243, ECO:0000269|PubMed:8301230, ECO:0000269|PubMed:8325986, ECO:0000269|PubMed:8486765, ECO:0000269|PubMed:8728326, ECO:0000269|PubMed:8778602, ECO:0000269|PubMed:8858123, ECO:0000269|PubMed:8872057, ECO:0000269|PubMed:8956048, ECO:0000269|PubMed:8956052, ECO:0000269|PubMed:9279761, ECO:0000269|PubMed:9298816, ECO:0000269|PubMed:9498099, ECO:0000269|PubMed:9662394, ECO:0000269|PubMed:9714430, ECO:0000269|PubMed:9719626}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Glycerolipid metabolism - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Familial lipoprotein lipase deficiency;Glycerolipid Metabolism;Glycerol Kinase Deficiency;D-glyceric acidura;Fatty Acid Beta Oxidation;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;miR-targeted genes in adipocytes - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Transcriptional regulation of white adipocyte differentiation;Alzheimers Disease;Adipogenesis;Aryl Hydrocarbon Receptor;Triacylglyceride Synthesis;Composition of Lipid Particles;Angiopoietin Like Protein 8 Regulatory Pathway;PPAR signaling pathway;Statin Pathway;role of ppar-gamma coactivators in obesity and thermogenesis;Vitamin A and Carotenoid Metabolism;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;mechanism of gene regulation by peroxisome proliferators via ppara;visceral fat deposits and the metabolic syndrome;Chylomicron remodeling;Metabolism;Transport of small molecules;Metabolism of vitamins and cofactors;Glycerophospholipid metabolism;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Retinoid metabolism and transport;G alpha (i) signalling events;Plasma lipoprotein remodeling;Visual phototransduction;GPCR downstream signalling
(Consensus)
Intolerance Scores
- loftool
- 0.197
- rvis_EVS
- 0.53
- rvis_percentile_EVS
- 80.96
Haploinsufficiency Scores
- pHI
- 0.361
- hipred
- N
- hipred_score
- 0.453
- ghis
- 0.515
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lpl
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- fatty acid biosynthetic process;triglyceride metabolic process;phospholipid metabolic process;response to cold;response to bacterium;response to glucose;positive regulation of macrophage derived foam cell differentiation;positive regulation of cholesterol storage;positive regulation of sequestering of triglyceride;triglyceride biosynthetic process;triglyceride catabolic process;chylomicron remodeling;very-low-density lipoprotein particle remodeling;response to drug;cholesterol homeostasis;positive regulation of inflammatory response;regulation of lipoprotein lipase activity;low-density lipoprotein particle mediated signaling;triglyceride homeostasis;positive regulation of chemokine secretion
- Cellular component
- extracellular region;extracellular space;plasma membrane;cell surface;anchored component of membrane;very-low-density lipoprotein particle;chylomicron
- Molecular function
- lipoprotein lipase activity;phospholipase activity;triglyceride lipase activity;signaling receptor binding;protein binding;heparin binding;triglyceride binding;apolipoprotein binding