LPL

Summary

LPL (lipoprotein lipase, HGNC:6677) is a protein-coding gene on chromosome 8p21.3, encoding Lipoprotein lipase (P06858). Key enzyme in triglyceride metabolism.

LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism.

Source: NCBI Gene 4023 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial lipoprotein lipase deficiency (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 315
• Clinical variants (ClinVar): 910 total — 87 pathogenic, 58 likely-pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6677
Approved symbol	LPL
Name	lipoprotein lipase
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175445
Ensembl biotype	protein_coding
OMIM	609708
Entrez	4023

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000519773, ENST00000520959, ENST00000521994, ENST00000522701, ENST00000523696, ENST00000524029, ENST00000650287, ENST00000650478, ENST00000900196, ENST00000965928, ENST00000965929, ENST00000965930, ENST00000965931, ENST00000965932

RefSeq mRNA: 1 — MANE Select: NM_000237 NM_000237

CCDS: CCDS6012

Canonical transcript exons

ENST00000650287 — 10 exons

Exon	Start	End
ENSE00001206539	19965310	19967259
ENSE00001206542	19960901	19961083
ENSE00001206548	19959260	19959380
ENSE00001206552	19955841	19956083
ENSE00001206556	19954120	19954353
ENSE00001206558	19953310	19953421
ENSE00001206561	19951769	19951948
ENSE00002728530	19962115	19962219
ENSE00003469588	19948180	19948340
ENSE00003833423	19939253	19939528

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 99.87.

FANTOM5 (CAGE): breadth broad, TPM avg 96.2636 / max 9562.1423, expressed in 683 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87603	91.3675	644
87604	4.2817	298
87605	0.6144	257

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	99.87	gold quality
trigeminal ganglion	UBERON:0001675	99.82	gold quality
dorsal root ganglion	UBERON:0000044	99.79	gold quality
heart right ventricle	UBERON:0002080	99.79	gold quality
left ventricle myocardium	UBERON:0006566	99.50	gold quality
cardiac ventricle	UBERON:0002082	99.26	gold quality
heart left ventricle	UBERON:0002084	99.24	gold quality
adipose tissue	UBERON:0001013	99.17	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.01	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.99	gold quality
omental fat pad	UBERON:0010414	98.96	gold quality
peritoneum	UBERON:0002358	98.88	gold quality
apex of heart	UBERON:0002098	98.86	gold quality
tibial nerve	UBERON:0001323	98.72	gold quality
connective tissue	UBERON:0002384	98.59	gold quality
diaphragm	UBERON:0001103	98.44	gold quality
sural nerve	UBERON:0015488	98.13	gold quality
pericardium	UBERON:0002407	98.04	gold quality
cortical plate	UBERON:0005343	97.95	gold quality
right lung	UBERON:0002167	97.86	gold quality
trabecular bone tissue	UBERON:0002483	97.75	gold quality
tibia	UBERON:0000979	97.66	gold quality
visceral pleura	UBERON:0002401	97.58	gold quality
deltoid	UBERON:0001476	97.54	gold quality
middle frontal gyrus	UBERON:0002702	97.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.43	gold quality
synovial joint	UBERON:0002217	97.29	gold quality
myocardium	UBERON:0002349	97.28	gold quality
body of tongue	UBERON:0011876	97.26	gold quality
lower lobe of lung	UBERON:0008949	97.25	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	469.62
E-HCAD-4	yes	19.70
E-CURD-112	yes	9.82
E-MTAB-8271	no	419.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, BMP2, CEBPA, CNBP, CREB1, CRP, ESR1, FOS, FOXO1, GLI2, HDAC9, IFI16, IFNG, INS, JUN, LRP3, NCOR2, NFKB1, NFYA, NR1H2, NR1H3, NR3C1, POU1F1, POU2F1, PPARA, PPARD, PPARG, RELA, RXRA, SP1, SP3, SREBF1, STAT1, TBP, TBPL2, TFAP2A, TGFB1, TNF, TSC22D3

miRNA regulators (miRDB)

97 targeting LPL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Literature-anchored findings (GeneRIF, showing 40)

• role of Sp1 and Sp3 in interferon-gamma mediated suppression of gene transcription (PMID:11796707)
• Peroxisome proliferator-activated receptor (PPARalpha and PPARgamma) agonists decrease lipoprotein lipase secretion and glycated LDL uptake by human macrophages. (PMID:11852057)
• Spontaneously occurring dissociation of LPL dimer into monomers is accelerated in exon 5 mutants, resulting in conformational changes which result in loss of LPL catalytic activity. (PMID:11893776)
• lipoprotein lipase cannot be a major factor in pathogenesis of Alzheimer’s disease (PMID:11897170)
• Low mass in preheparin serum of type 2 diabetes mellitus patients and its recovery with insulin therapy. (PMID:11947965)
• results suggest that the nature of the mutation in the LPL gene modifies the relationship of HDL particle size to other metabolic variables and secondary factors such as abdominal obesity and gender. (PMID:11996946)
• Variants in gene relate to presence and degree of microalbuminuria in Type II diabetes (PMID:12107736)
• The S447X mutation is associated with anti-atherogenic effects on TG and HDL cholesterol in both genders, and with a moderate protective effect on risk of ischemic heart disease in men. (PMID:12208477)
• LPL is bound to postprandial triglyceride-rich lipoproteins and mediates their hepatic clearance in vivo. (PMID:12226739)
• molecular modeling of its dimeric structure (PMID:12230584)
• variations in genes affecting the removal rate of triglycerides (TG) from plasma significantly influence the lipid phenotypic expression of familial combined hyperlipidemia (PMID:12370850)
• some single-nucleotide polymorphisms in the LPL gene among Chinese associated with abnormal lipid and lipoprotein profiles and predisposition to coronary heart disease, and they are gender-specific. (PMID:12408999)
• LPL has a role in atherosclerosis, chylomicronaemia, obesity, Alzheimer’s disease, and dyslipidaemia associated with diabetes, insulin resistance, and infection [review] (PMID:12483461)
• LPL could play a key role in the differentiation of Neuro-2A cells and in the pathophysiological effects of oxidative stress in several neurodegenerative disorders (PMID:12501246)
• conclude that type IIB VLDL-1 and VLDL-2 induce triglyceride accumulation in monocyte-macrophages primarily by the lipolytic action of LPL, which may involve stabilization and activation of the enzyme, rather than modulation of enzyme production (PMID:12573449)
• H+ allele of the lipoprotein lipase gene HindIII polymorphism is associated with higher plasma triglyceride and lower HDL-cholesterol levels in Chinese patients with early-onset diabetes (PMID:12647273)
• LPL enzyme deficiency causes elevated plasma triglyceride level and subsequent insulin resistance; increased free fatty acids combined with insulin resistance promote gluconeogenesis and hyperglycemia, a vicious circle leading to type 2 diabetes. (PMID:12655575)
• results demonstrate a direct effect of prolactin, via functional prolactin receptors, in reducing the lipoprotein lipase activity in human adipose tissue (PMID:12679477)
• the LPL association with lipid profile is more likely attributable to the functional S447X rather than the nonfunctional exon 10 SNP (PMID:12687649)
• The LPL D9N genotype was a significant predictor of both baseline carotid plaque area and progression. Heterozygotes for the N9 allele had higher values than did LPL D9/D9 homozygotes. D9N genotype may be a determinant of atherosclerosis. (PMID:12690214)
• data indicate an important role of endoplasmic reticulum-based chaperones for the folding/dimerization of lipoprotein lipase (PMID:12740382)
• LPL gene and associated regions might contribute to individual blood pressure variation and hypertension in the Chinese population (PMID:12746411)
• Lipoprotein lipase gene polymorphisms might be involved in predisposition to coronary artery disease (PMID:12747600)
• LPL enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and their relationship with Lp(A-I) and Lp(A-I,A-II) (PMID:12777470)
• LPL lipolysis of emulsion triolein was retarded in chylomicron-free human plasma compared with the hydrolysis activated by isolated apolipoprotein C-II. (PMID:12782148)
• LPL 44X alleles were associated with moderately increased LDL peak particle size. (PMID:12818414)
• findings of variation near the LPL gene support the proposition that a region near the lipoprotein lipase gene or the lipoprotein lipase gene itself might contribute to the individual blood pressure variation in Chinese (PMID:12862202)
• lipoprotein lipase has a protective role against coronary artery disease in Mexican-Americans (PMID:12865761)
• did not find significant effects of lipoprotein lipase HindIII or PvuII polymorphisms on the fasting lipids but HindIII variation was associated with higher triglyceride postprandial peak (PMID:12915220)
• These results by showing modulation of association between S447X variant of the LPL gene and serum TG by C-514T variant of the HL gene underscore the importance of gene-gene interactions in the assessment of genetic effects on complex traits (PMID:14564687)
• Muscle can synthesize tethered, dimeric LpL, but efficient production of this enzyme leading to secretion, and physiological function appears to favor secretion of a noncovalent dimer composed of monomeric subunits. (PMID:14570890)
• In Japanese, poorly controlled type 2 diabetic men had more unfavorable lipid profile than did women counterparts, which may be associated with decreased plasma LPL levels. (PMID:14581156)
• results imply that systemic elevation of lipoprotein lipase expression may be potentially useful for the treatment of hyperlipidemias, obesity, and insulin resistance (PMID:14660566)
• Variation in the LPL gene plays a role in determining insulin resistance in Mexican Americans. (PMID:14693718)
• Macrophage LPL activity correlated with body mass index and fat mass. Incubation of patient macrophages with IGF-I for 24 h or differentiation of monocytes from GH-deficient patients into macrophages in presence of this growth factor decreased LPL. (PMID:14764824)
• TRL-bound LPL activity increases in the postprandial state and is strongly reduced in type 2 diabetes, contributing to postprandial hypertriglyceridemia (PMID:14967813)
• both hyperglycemia and hyperinsulinemia plus hyperglycemia reduced LPL activity to 60 % (PMID:14984315)
• LPL-mediated fatty acid uptake is an inefficient process, but may be more efficient in muscle than in adipose tissue. (PMID:14988233)
• Activity may explain the difference in LDL lipoprotein size in diabetic and nondiabetic people. (PMID:14988305)
• Data show that human lipoprotein lipase significantly inhibited spontaneous human natural killer cells, but not lymphokine-activated killer cytotoxic activity against bovine pulmonary endothelial cells. (PMID:15051515)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpla	ENSDARG00000087697
danio_rerio	lplb	ENSDARG00000098720
mus_musculus	Lpl	ENSMUSG00000015568
rattus_norvegicus	Lpl	ENSRNOG00000012181
drosophila_melanogaster	CG5162	FBGN0030828
drosophila_melanogaster	CG6675	FBGN0032973
drosophila_melanogaster	CG6472	FBGN0034166
drosophila_melanogaster	CG5665	FBGN0036977
drosophila_melanogaster	sxe2	FBGN0038398
drosophila_melanogaster	CG4582	FBGN0039344
drosophila_melanogaster	CG6296	FBGN0039470
drosophila_melanogaster	CG6295	FBGN0039471
drosophila_melanogaster	CG17192	FBGN0039472
drosophila_melanogaster	CG17191	FBGN0039473
drosophila_melanogaster	CG6283	FBGN0039474
drosophila_melanogaster	CG6277	FBGN0039475
drosophila_melanogaster	CG6271	FBGN0039476
drosophila_melanogaster	CG4267	FBGN0264979
drosophila_melanogaster	CG18258	FBGN0265267

Paralogs (9): LIPG (ENSG00000101670), PLA1A (ENSG00000144837), LIPH (ENSG00000163898), LIPC (ENSG00000166035), PNLIP (ENSG00000175535), PNLIPRP1 (ENSG00000187021), LIPI (ENSG00000188992), PNLIPRP3 (ENSG00000203837), PNLIPRP2 (ENSG00000266200)

Protein

Protein identifiers

Lipoprotein lipase — P06858 (reviewed: P06858)

Alternative names: Phospholipase A1

All UniProt accessions (7): A0A1B1RVA9, A0A3B3IT60, E5RHN7, E5RJI0, E5RJZ4, P06858, E7EW14

UniProt curated annotations — full annotation on UniProt →

Function. Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage. Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity. Mediates margination of triglyceride-rich lipoprotein particles in capillaries. Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans.

Subunit / interactions. Homodimer. Interacts with GPIHBP1 with 1:1 stoichiometry. Interacts with APOC2; the interaction activates LPL activity in the presence of lipids. Interaction with heparan sulfate proteoglycans is required to protect LPL against loss of activity. Associates with lipoprotein particles in blood plasma. Interacts with LMF1 and SEL1L; interaction with SEL1L is required to prevent aggregation of newly synthesized LPL in the endoplasmic reticulum (ER), and for normal export of LPL from the ER to the extracellular space. Interacts with SORL1; SORL1 acts as a sorting receptor, promoting LPL localization to endosomes and later to lysosomes, leading to degradation of newly synthesized LPL.

Subcellular location. Cell membrane. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Detected in blood plasma. Detected in milk (at protein level).

Post-translational modifications. Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity.

Disease relevance. Hyperlipoproteinemia 1 (HLPP1) [MIM:238600] An autosomal recessive metabolic disorder characterized by defective breakdown of dietary fats, impaired clearance of chylomicrons from plasma causing the plasma to have a milky appearance, and severe hypertriglyceridemia. On a normal diet, patients often present with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive xanthomata, and massive hypertriglyceridemia, sometimes complicated with acute pancreatitis. The disease is caused by variants affecting the gene represented in this entry. Hyperlipidemia, familial combined, 3 (FCHL3) [MIM:144250] A disorder characterized by a variable pattern of elevated levels of serum total cholesterol, triglycerides or both. It is observed in a percentage of individuals with premature coronary heart disease. FCHL3 inheritance is autosomal dominant. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. The apolipoprotein APOC2 acts as a coactivator of LPL activity. Ca(2+) binding promotes protein stability and formation of the active homodimer. Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4. Inhibited by NaCl.

Similarity. Belongs to the AB hydrolase superfamily. Lipase family.

RefSeq proteins (1): NP_000228* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000734	TAG_lipase	Family
IPR001024	PLAT/LH2_dom	Domain
IPR002330	Lipo_Lipase	Family
IPR013818	Lipase	Domain
IPR016272	Lipase_LIPH	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR033906	Lipase_N	Domain
IPR036392	PLAT/LH2_dom_sf	Homologous_superfamily

Pfam: PF00151, PF01477

Enzyme classification (BRENDA):

• EC 3.1.1.34 — lipoprotein lipase (BRENDA: 20 organisms, 68 substrates, 86 inhibitors, 21 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TRIOLEIN	0.0002–2.5	5
VERY-LOW-DENSITY LIPOPROTEIN	0.97–1.68	4
CHYLOMICRON	1.12–1.77	2
TRIACYLGLYCEROL	4.74–6.09	2
VERY-LOW-DENSITY LIPOPROTEINS	0.026–0.053	2
1,2-DI-O-LAURYL-RAC-GLYCERO-3-GLUTARIC ACID 6’-M	0.0004	1

Catalyzed reactions (Rhea), 6 shown:

• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)
• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:18689)
• 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = di-(9Z)-octadecenoylglycerol + (9Z)-octadecenoate + H(+) (RHEA:38575)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z-octadecenoyl)-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+) (RHEA:38699)
• 1,2,3-tributanoylglycerol + H2O = dibutanoylglycerol + butanoate + H(+) (RHEA:40475)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:41384)

UniProt features (162 total): sequence variant 75, strand 26, mutagenesis site 17, helix 14, turn 5, disulfide bond 5, region of interest 5, binding site 4, active site 3, modified residue 3, glycosylation site 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6OAU	X-RAY DIFFRACTION	2.48
6E7K	X-RAY DIFFRACTION	2.8
6WN4	X-RAY DIFFRACTION	2.8
6OB0	X-RAY DIFFRACTION	2.81
6OAZ	X-RAY DIFFRACTION	3.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06858-F1	91.36	0.82

Antibody-complex structures (SAbDab): 1 — 6WN4

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 268 (charge relay system); 159 (nucleophile); 183 (charge relay system)

Ligand- & substrate-binding residues (4): 194; 197; 199; 202

Post-translational modifications (3): 121, 191, 343

Disulfide bonds (5): 54–67, 243–266, 291–310, 302–305, 445–465

Glycosylation sites (2): 70, 386

Mutagenesis-validated functional residues (17):

Position	Phenotype
159	loss of enzyme activity with triolein and tributyrin.
183	loss of enzyme activity with triolein and tributyrin.
199	loss of enzyme activity.
201	no effect on enzyme activity.
202	loss of enzyme activity.
244–264	reduced triglyceride hydrolase activity and increased phospholipase activity.
245–263	loss of both triglyceride hydrolase and phospholipase activity.
245–248	loss of triglyceride hydrolase activity while phospholipase activity remains intact.
262–263	loss of triglyceride hydrolase activity while phospholipase activity remains intact.
268	loss of enzyme activity with triolein and tributyrin.
417	loss of interaction with lipoprotein particles, but no effect on interaction with gpihbp1; when associated with 420-a-a-
420–421	loss of interaction with lipoprotein particles, but no effect on interaction with gpihbp1; when associated with a-417.
430	impaired heparin-binding; when associated with n-432 and n-437.
432	impaired heparin-binding; when associated with n-430 and n-437.
434	impaired heparin-binding; when associated with n-430 and n-432.

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes
R-HSA-8963901	Chylomicron remodeling
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-2187338	Visual phototransduction
R-HSA-382551	Transport of small molecules
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-74160	Gene expression (Transcription)
R-HSA-8963899	Plasma lipoprotein remodeling
R-HSA-9709957	Sensory Perception
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9843745	Adipogenesis
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 520 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_ACYLGLYCEROL_HOMEOSTASIS, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_INFLAMMATORY_RESPONSE, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN

GO Biological Process (30): retinoid metabolic process (GO:0001523), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), triglyceride metabolic process (GO:0006641), phospholipid metabolic process (GO:0006644), response to bacterium (GO:0009617), response to glucose (GO:0009749), positive regulation of macrophage derived foam cell differentiation (GO:0010744), positive regulation of lipid storage (GO:0010884), positive regulation of cholesterol storage (GO:0010886), triglyceride catabolic process (GO:0019433), cellular response to nutrient (GO:0031670), positive regulation of chemokine production (GO:0032722), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-6 production (GO:0032755), positive regulation of tumor necrosis factor production (GO:0032760), chylomicron remodeling (GO:0034371), very-low-density lipoprotein particle remodeling (GO:0034372), high-density lipoprotein particle remodeling (GO:0034375), very-low-density lipoprotein particle clearance (GO:0034447), cholesterol homeostasis (GO:0042632), positive regulation of fat cell differentiation (GO:0045600), positive regulation of inflammatory response (GO:0050729), low-density lipoprotein particle mediated signaling (GO:0055096), triglyceride homeostasis (GO:0070328), cellular response to fatty acid (GO:0071398), positive regulation of adipose tissue development (GO:1904179), positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (17): lipoprotein lipase activity (GO:0004465), glycerophospholipase activity (GO:0004620), triacylglycerol lipase activity (GO:0004806), signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), heparin binding (GO:0008201), glycerophospholipid phospholipase A1 activity (GO:0008970), apolipoprotein binding (GO:0034185), protein homodimerization activity (GO:0042803), heparan sulfate proteoglycan binding (GO:0043395), protein-membrane adaptor activity (GO:0043495), lipoprotein particle binding (GO:0071813), protein binding (GO:0005515), lipase activity (GO:0016298), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), very-low-density lipoprotein particle (GO:0034361), chylomicron (GO:0042627), catalytic complex (GO:1902494), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Plasma lipoprotein remodeling	2
Adipogenesis	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Transport of small molecules	1
Metabolism	1
Gene expression (Transcription)	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1
Plasma lipoprotein assembly, remodeling, and clearance	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Developmental Biology	1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
lipid metabolic process	2
positive regulation of cytokine production	2
triglyceride-rich lipoprotein particle remodeling	2
protein binding	2
hydrolase activity, acting on ester bonds	2
diterpenoid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
acylglycerol metabolic process	1
organophosphate metabolic process	1
response to other organism	1
response to hexose	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
regulation of lipid storage	1
lipid storage	1
positive regulation of cellular process	1
positive regulation of lipid localization	1
cholesterol storage	1
positive regulation of lipid storage	1
regulation of cholesterol storage	1
triglyceride metabolic process	1
acylglycerol catabolic process	1
response to nutrient	1
cellular response to nutrient levels	1
cellular response to chemical stimulus	1
chemokine production	1
regulation of chemokine production	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1

Protein interactions and networks

STRING

2030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPL	GPIHBP1	Q8IV16	998
LPL	APOC2	P02655	983
LPL	APOC3	P02656	961
LPL	ANGPTL4	Q9BY76	930
LPL	ANGPTL3	Q9Y5C1	922
LPL	LMF1	Q96S06	916
LPL	APOE	P02649	908
LPL	LIPE	Q05469	899
LPL	FABP4	P15090	882
LPL	APOA5	Q6Q788	880
LPL	APOB	P04114	875
LPL	CETP	P11597	874
LPL	PPARG	P37231	874
LPL	INS	P01308	854
LPL	CD36	P16671	840

IntAct

79 interactions, top by confidence:

A	B	Type	Score
GPIHBP1	LPL	psi-mi:“MI:0407”(direct interaction)	0.740
GPIHBP1	LPL	psi-mi:“MI:0403”(colocalization)	0.740
GPIHBP1	LPL	psi-mi:“MI:0915”(physical association)	0.740
LPL	GPIHBP1	psi-mi:“MI:0915”(physical association)	0.740
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
DCX	ZBTB5	psi-mi:“MI:0914”(association)	0.670
	LPL	psi-mi:“MI:1355”(lipid cleavage)	0.620
	LPL	psi-mi:“MI:0407”(direct interaction)	0.620
NME4	LPL	psi-mi:“MI:0915”(physical association)	0.560
NPHP1	LPL	psi-mi:“MI:0915”(physical association)	0.560
PRRG2	LPL	psi-mi:“MI:0915”(physical association)	0.560
PSMD9	LPL	psi-mi:“MI:0915”(physical association)	0.560
EIF2B4	LPL	psi-mi:“MI:0915”(physical association)	0.560
LPL	PRMT5	psi-mi:“MI:0915”(physical association)	0.560
TGOLN2	LPL	psi-mi:“MI:0915”(physical association)	0.560
SNX12	LPL	psi-mi:“MI:0915”(physical association)	0.560
SLFN12	LPL	psi-mi:“MI:0915”(physical association)	0.560
TMEM185A	LPL	psi-mi:“MI:0915”(physical association)	0.560
CCDC26	LPL	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	LPL	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (40): LPL (Two-hybrid), LPL (Two-hybrid), LPL (Two-hybrid), UBE2Z (Two-hybrid), LPL (Two-hybrid), COPS6 (Two-hybrid), KIAA1377 (Two-hybrid), LUC7L2 (Two-hybrid), LPL (Two-hybrid), LPL (Affinity Capture-MS), LPL (Reconstituted Complex), VLDLR (Reconstituted Complex), LRP1 (Reconstituted Complex), LRP1 (Reconstituted Complex), LPL (Reconstituted Complex)

ESM2 similar proteins: A1A4K5, A2BGL3, J3RZ81, O46559, O46647, P06858, P07867, P11150, P11151, P11152, P11153, P11602, P13612, P22413, P27656, P28825, P49060, P49923, P55031, P97535, Q06000, Q08761, Q13219, Q16819, Q29524, Q2TBF2, Q32PY2, Q3SZ79, Q53H76, Q5E9H0, Q5NDE3, Q5NDE4, Q5NDE5, Q5NDE8, Q5RBQ5, Q5XGE9, Q641F6, Q64230, Q64610, Q6DBU8

Diamond homologs: A2VBC4, A5PK46, C0HLL3, D7EZN2, J3RZ81, O46559, O46647, O88354, P00591, P06857, P06858, P0CH47, P0CH86, P11150, P11151, P11152, P11153, P11602, P16233, P17892, P27656, P27657, P29183, P49060, P49923, P50903, P51528, P53357, P54315, P54316, P54317, P54318, P55031, P81139, P83629, P97535, Q02157, Q06000, Q06478, Q17RR3

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
APOA5	“up-regulates activity”	LPL	binding
APOC2	“up-regulates activity”	LPL
IFNG	“down-regulates quantity by repression”	LPL	“transcriptional regulation”
PPARA	“up-regulates activity”	LPL
APOC3	“down-regulates activity”	LPL
PRL	“down-regulates activity”	LPL
CRP	“up-regulates quantity by expression”	LPL	“transcriptional regulation”
TNF	“down-regulates quantity by repression”	LPL	“transcriptional regulation”
IL1B	“down-regulates activity”	LPL
INS	“up-regulates quantity by expression”	LPL	“transcriptional regulation”
INS	“up-regulates activity”	LPL
TGFB1	“up-regulates quantity by expression”	LPL	“transcriptional regulation”
IFNA10	“down-regulates activity”	LPL

Disease & clinical

Clinical variants and AI predictions

ClinVar

910 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	87
Likely pathogenic	58
Uncertain significance	266
Likely benign	362
Benign	59

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066636	NM_000237.3(LPL):c.805G>A (p.Glu269Lys)	Pathogenic
1069128	NM_000237.3(LPL):c.474C>G (p.Tyr158Ter)	Pathogenic
1070373	NM_000237.3(LPL):c.1263G>A (p.Trp421Ter)	Pathogenic
1075531	NM_000237.3(LPL):c.1172_1175del (p.Ser390_Phe391insTer)	Pathogenic
1076739	NM_000237.3(LPL):c.1003C>T (p.Gln335Ter)	Pathogenic
1076886	NC_000008.10:g.(?19810811)(19811874_?)del	Pathogenic
1370928	NM_000237.3(LPL):c.811del (p.Ser271fs)	Pathogenic
1399464	NM_000237.3(LPL):c.138del (p.Glu47fs)	Pathogenic
1401888	NM_000237.3(LPL):c.566_567del (p.Asn188_Phe189insTer)	Pathogenic
1418720	NM_000237.3(LPL):c.932del (p.Asn311fs)	Pathogenic
1427499	NM_000237.3(LPL):c.572_588del (p.Tyr191fs)	Pathogenic
1431010	NM_000237.3(LPL):c.46_47del (p.Gln16fs)	Pathogenic
1448765	NM_000237.3(LPL):c.1259G>A (p.Trp420Ter)	Pathogenic
1452004	NM_000237.3(LPL):c.763_766del (p.Arg255fs)	Pathogenic
1452072	NM_000237.3(LPL):c.590G>T (p.Arg197Leu)	Pathogenic
1455355	NM_000237.3(LPL):c.355del (p.Glu119fs)	Pathogenic
1455947	NM_000237.3(LPL):c.10_19del (p.Lys4fs)	Pathogenic
1458039	NM_000237.3(LPL):c.919A>T (p.Lys307Ter)	Pathogenic
1459737	NC_000008.10:g.(?19796711)(19797049_?)del	Pathogenic
1520	LPL, INS	Pathogenic
1521	NM_000237.3(LPL):c.898_1019-1234dup	Pathogenic
1523	NG_008855.2:g.(51625_55052)_(57638_59124)del	Pathogenic
1525	NM_000237.3(LPL):c.811T>A (p.Ser271Thr)	Pathogenic
1526	NM_000237.3(LPL):c.250-1G>A	Pathogenic
1528	NM_000237.3(LPL):c.693C>G (p.Asp231Glu)	Pathogenic
1532	NM_000237.3(LPL):c.506G>A (p.Gly169Glu)	Pathogenic
1533	NM_000237.3(LPL):c.548A>G (p.Asp183Gly)	Pathogenic
1535	NM_000237.3(LPL):c.249+1G>A	Pathogenic
1536	NM_000237.3(LPL):c.264T>A (p.Tyr88Ter)	Pathogenic
1537	NM_000237.3(LPL):c.1227G>A (p.Trp409Ter)	Pathogenic

SpliceAI

1417 predictions. Top by Δscore:

Variant	Effect	Δscore
8:19948175:TCCA:T	acceptor_loss	1.0000
8:19948178:A:AG	acceptor_gain	1.0000
8:19948179:G:GG	acceptor_gain	1.0000
8:19948179:GAA:G	acceptor_gain	1.0000
8:19948179:GAAA:G	acceptor_gain	1.0000
8:19948336:GGACG:G	donor_gain	1.0000
8:19948337:GACG:G	donor_gain	1.0000
8:19948337:GACGG:G	donor_gain	1.0000
8:19948341:G:GA	donor_loss	1.0000
8:19948341:G:GG	donor_gain	1.0000
8:19951947:AGG:A	donor_loss	1.0000
8:19951948:GGTA:G	donor_loss	1.0000
8:19951949:G:T	donor_loss	1.0000
8:19953306:A:AG	acceptor_gain	1.0000
8:19953386:G:GT	donor_gain	1.0000
8:19953422:G:GG	donor_gain	1.0000
8:19953422:GT:G	donor_loss	1.0000
8:19953423:T:A	donor_loss	1.0000
8:19954117:A:AG	acceptor_gain	1.0000
8:19954117:AAG:A	acceptor_gain	1.0000
8:19954118:A:AG	acceptor_gain	1.0000
8:19954118:AG:A	acceptor_gain	1.0000
8:19954119:G:A	acceptor_gain	1.0000
8:19954119:G:GA	acceptor_gain	1.0000
8:19954119:GGC:G	acceptor_gain	1.0000
8:19954119:GGCCT:G	acceptor_gain	1.0000
8:19954350:GGAG:G	donor_gain	1.0000
8:19954351:G:GT	donor_gain	1.0000
8:19954351:GAG:G	donor_gain	1.0000
8:19954351:GAGGT:G	donor_loss	1.0000

AlphaMissense

3139 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:19954305:T:A	C243S	1.000
8:19954306:G:C	C243S	1.000
8:19955874:G:C	R270P	1.000
8:19948335:T:A	W82R	0.999
8:19948335:T:C	W82R	0.999
8:19948337:G:C	W82C	0.999
8:19948337:G:T	W82C	0.999
8:19951790:T:A	W91R	0.999
8:19951790:T:C	W91R	0.999
8:19951792:G:C	W91C	0.999
8:19951792:G:T	W91C	0.999
8:19951856:T:A	W113R	0.999
8:19951856:T:C	W113R	0.999
8:19951881:A:G	Y121C	0.999
8:19953356:G:T	S159I	0.999
8:19953361:G:A	G161R	0.999
8:19953361:G:C	G161R	0.999
8:19953362:G:A	G161E	0.999
8:19954123:T:C	L182P	0.999
8:19954126:A:G	D183G	0.999
8:19954126:A:T	D183V	0.999
8:19954143:T:C	F189L	0.999
8:19954144:T:G	F189C	0.999
8:19954145:T:A	F189L	0.999
8:19954145:T:G	F189L	0.999
8:19954171:T:A	L198H	0.999
8:19954185:G:C	A203P	0.999
8:19954186:C:A	A203E	0.999
8:19954206:C:G	H210D	0.999
8:19954243:G:A	G222E	0.999

dbSNP variants (sampled 300 via entrez): RS1000160107 (8:19951488 A>C), RS1000225315 (8:19965749 A>G), RS1000237995 (8:19945415 A>G), RS1000365481 (8:19940315 G>GGGTT), RS1000419432 (8:19940092 C>G), RS1000812683 (8:19964743 G>T), RS1000834483 (8:19965452 T>C), RS1000949160 (8:19960082 C>A,T), RS1001010023 (8:19948882 A>T), RS1001093111 (8:19964102 G>A), RS1001113397 (8:19954903 A>G), RS1001115528 (8:19940098 C>T), RS1001140011 (8:19939916 G>A,C), RS1001195074 (8:19964889 A>C,G), RS1001197526 (8:19944105 G>T)

Disease associations

OMIM: gene MIM:609708 | disease phenotypes: MIM:144250, MIM:238600, MIM:246650, MIM:115200

GenCC curated gene-disease

Disease	Classification	Inheritance
familial lipoprotein lipase deficiency	Definitive	Autosomal recessive
hyperlipidemia, familial combined, LPL related	Strong	Autosomal dominant

Mondo (5): hyperlipidemia, familial combined, LPL related (MONDO:0007759), familial lipoprotein lipase deficiency (MONDO:0009387), lipase deficiency, combined (MONDO:0009527), hypertriglyceridemia (MONDO:0005347), dilated cardiomyopathy 1A (MONDO:0007269)

Orphanet (4): Familial lipoprotein lipase deficiency (Orphanet:309015), Familial chylomicronemia syndrome (Orphanet:444490), Familial lipase maturation factor 1 deficiency (Orphanet:535453), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751)

HPO phenotypes

23 total (24 of 23 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000660	Lipemia retinalis
HP:0000952	Jaundice
HP:0001013	Eruptive xanthomas
HP:0001114	Xanthelasma
HP:0001433	Hepatosplenomegaly
HP:0001658	Myocardial infarction
HP:0001735	Acute pancreatitis
HP:0001744	Splenomegaly
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002574	Episodic abdominal pain
HP:0003077	Hyperlipidemia
HP:0003124	Hypercholesterolemia
HP:0003141	Increased LDL cholesterol concentration
HP:0003362	Increased VLDL cholesterol concentration
HP:0004416	Precocious atherosclerosis
HP:0011462	Young adult onset
HP:0012238	Increased circulating chylomicron concentration
HP:0031028	Lactescent serum
HP:0031798	Elevated circulating apolipoprotein B concentration
HP:0031800	Elevated circulating apolipoprotein A-II concentration
HP:0002155	Hypertriglyceridemia

GWAS associations

315 associations (top):

Study	Trait	p-value
GCST000026_1	Triglycerides	5.000000e-07
GCST000133_5	HDL cholesterol	9.000000e-23
GCST000135_9	HDL cholesterol	4.000000e-19
GCST000137_1	Triglycerides	5.000000e-12
GCST000138_7	Triglycerides	2.000000e-28
GCST000139_2	Triglycerides	4.000000e-22
GCST000184_1	Waist circumference and related phenotypes	5.000000e-06
GCST000240_1	HDL cholesterol	3.000000e-11
GCST000278_11	Hyperactive-impulsive symptoms	2.000000e-06
GCST000286_2	Triglycerides	2.000000e-41
GCST000288_9	HDL cholesterol	6.000000e-18
GCST000289_2	Triglycerides	2.000000e-18
GCST000290_1	HDL cholesterol	2.000000e-34
GCST000292_9	Metabolic traits	5.000000e-08
GCST000533_16	Lipid metabolism phenotypes	2.000000e-17
GCST000533_39	Lipid metabolism phenotypes	1.000000e-17
GCST000533_40	Lipid metabolism phenotypes	3.000000e-14
GCST000533_41	Lipid metabolism phenotypes	1.000000e-11
GCST000533_42	Lipid metabolism phenotypes	1.000000e-14
GCST000533_44	Lipid metabolism phenotypes	1.000000e-20
GCST000583_4	Hematological and biochemical traits	9.000000e-06
GCST000584_4	Triglycerides	9.000000e-14
GCST000737_4	Hypertriglyceridemia	2.000000e-07
GCST000753_16	Metabolic syndrome	2.000000e-10
GCST000755_27	HDL cholesterol	1.000000e-97
GCST000758_14	Triglycerides	2.000000e-115
GCST000805_8	HDL cholesterol	8.000000e-26
GCST000809_7	Triglycerides	4.000000e-26
GCST000974_15	HDL cholesterol	2.000000e-09
GCST001003_4	Metabolic syndrome	2.000000e-09

EFO canonical traits (29, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004529	lipid measurement
EFO:0000195	metabolic syndrome
EFO:0004723	coronary artery calcification
EFO:0004458	C-reactive protein measurement
EFO:0007874	gut microbiome measurement
EFO:0007929	triglyceride:HDL cholesterol ratio
EFO:0004340	body mass index
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0009132	cholesterol efflux capacity measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0009925	Antithrombotic agent use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004329	alcohol drinking
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004574	total cholesterol measurement
EFO:0005689	non-high density lipoprotein cholesterol measurement
EFO:0600007	fish oil supplement exposure measurement
EFO:0006925	lipoprotein A measurement
EFO:0004842	eosinophil count
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0007984	platelet component distribution width
EFO:0009188	Red cell distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008072	Hyperlipoproteinemia Type I	C16.320.565.398.465; C18.452.584.500.500.644.237; C18.452.584.563.465; C18.452.648.398.465
D015228	Hypertriglyceridemia	C18.452.584.500.500.851
C535904	Lipase deficiency combined (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2060 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,186 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL175247	ORLISTAT	4	38,186

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs320	Efficacy	3	fenofibrate	Hypertriglyceridemia
rs328	Efficacy	3	pravastatin

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs320	LPL	3	2.00	1	fenofibrate
rs328	LPL	3	2.75	1	pravastatin
rs1801177	LPL		0.00	0

ChEMBL bioactivities

14 potent at pChembl≥5 of 53 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.18	IC50	66	nM	ORLISTAT
6.70	IC50	200	nM	CHEMBL339297
5.85	IC50	1400	nM	CHEMBL485946
5.82	IC50	1500	nM	CHEMBL1952298
5.77	IC50	1690	nM	CHEMBL2381069
5.59	IC50	2560	nM	CHEMBL3093304
5.42	IC50	3800	nM	CHEMBL1952296
5.36	IC50	4400	nM	CHEMBL1952307
5.16	IC50	7000	nM	CHEMBL1952310
5.10	IC50	8000	nM	CHEMBL1952295
5.05	IC50	9000	nM	TOLYL BORONIC ACID
5.05	IC50	9000	nM	CHEMBL1952294
5.05	IC50	9000	nM	CHEMBL1952297
5.02	IC50	9600	nM	CHEMBL1952309

PubChem BioAssay actives

14 with measured affinity, of 100 total; 14 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Orlistat	1586815: Inhibition of recombinant human LPL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0660	uM
4-tert-butyl-N-[4-(5-methoxy-2-oxo-1,3,4-oxadiazol-3-yl)phenyl]benzamide	103972: Compound was tested to inhibit lipoprotein lipase (LPL)	ic50	0.2000	uM
(4-nonylphenyl)boronic acid	646971: Inhibition of human lipoprotein lipase expressed in HEK293 cells using bis-BD-PC and mono-BD-TG as substrate incubated for 10 mins prior to substrate addition by micelle assay	ic50	1.4000	uM
(4-undecylphenyl)boronic acid	646971: Inhibition of human lipoprotein lipase expressed in HEK293 cells using bis-BD-PC and mono-BD-TG as substrate incubated for 10 mins prior to substrate addition by micelle assay	ic50	1.5000	uM
S-[(2-fluorophenyl)methyl] N-(6-phenylhexyl)carbamothioate	746247: Inhibition of human LPL expressed in HEK293 cells using PED-A1 as substrate by spectrophotometry	ic50	1.6900	uM
2-[3-[(4-fluorophenyl)methyl]pyrrolidin-1-yl]-5-(trifluoromethyl)benzoic acid	1058526: Inhibition of recombinant human lipoprotein lipase using bis-BODIPY-FL C11-PC as substrate preincubated for 30 mins followed by substrate addition by FELA method	ic50	2.5600	uM
(4-pentylphenyl)boronic acid	646971: Inhibition of human lipoprotein lipase expressed in HEK293 cells using bis-BD-PC and mono-BD-TG as substrate incubated for 10 mins prior to substrate addition by micelle assay	ic50	3.8000	uM
4,4,5,5-tetramethyl-2-(4-phenylphenyl)-1,3,2-dioxaborolane	646968: Inhibition of human lipoprotein lipase expressed using recombinant adenovirus using glycerol-tri[9,10(n)-3H]oleate after 1 hr by vesicle assay	ic50	4.4000	uM
4,4,5,5-tetramethyl-2-(4-thiophen-2-ylphenyl)-1,3,2-dioxaborolane	646968: Inhibition of human lipoprotein lipase expressed using recombinant adenovirus using glycerol-tri[9,10(n)-3H]oleate after 1 hr by vesicle assay	ic50	7.0000	uM
(4-propylphenyl)boronic acid	646968: Inhibition of human lipoprotein lipase expressed using recombinant adenovirus using glycerol-tri[9,10(n)-3H]oleate after 1 hr by vesicle assay	ic50	8.0000	uM
(4-ethylphenyl)boronic acid	646968: Inhibition of human lipoprotein lipase expressed using recombinant adenovirus using glycerol-tri[9,10(n)-3H]oleate after 1 hr by vesicle assay	ic50	9.0000	uM
(4-heptylphenyl)boronic acid	646971: Inhibition of human lipoprotein lipase expressed in HEK293 cells using bis-BD-PC and mono-BD-TG as substrate incubated for 10 mins prior to substrate addition by micelle assay	ic50	9.0000	uM
(4-methylphenyl)boronic acid	646968: Inhibition of human lipoprotein lipase expressed using recombinant adenovirus using glycerol-tri[9,10(n)-3H]oleate after 1 hr by vesicle assay	ic50	9.0000	uM
2-[4-(furan-2-yl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane	646968: Inhibition of human lipoprotein lipase expressed using recombinant adenovirus using glycerol-tri[9,10(n)-3H]oleate after 1 hr by vesicle assay	ic50	9.6000	uM

CTD chemical–gene interactions

132 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects expression, affects cotreatment, increases expression, affects methylation (+2 more)	10
Rosiglitazone	affects transport, affects cotreatment, increases expression, increases reaction, decreases reaction	10
Dexamethasone	affects cotreatment, increases expression, decreases expression, decreases reaction, increases reaction (+1 more)	10
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression, decreases reaction, decreases expression, increases reaction (+1 more)	10
bisphenol S	affects cotreatment, increases expression, decreases expression	6
Valproic Acid	affects expression, affects cotreatment, decreases expression	5
Orlistat	decreases reaction, increases hydrolysis, increases uptake, increases activity, decreases activity	4
Estradiol	affects expression, affects binding, increases expression, affects cotreatment, decreases expression	4
bisphenol F	affects cotreatment, increases expression	3
very low density lipoprotein triglyceride	increases hydrolysis, increases abundance, decreases reaction, increases activity, affects reaction (+1 more)	3
T 0070907	decreases reaction, increases expression, affects cotreatment, decreases expression	3
Troglitazone	affects cotreatment, increases expression, increases metabolic processing	3
Bezafibrate	increases activity	3
Clofibrate	increases activity, increases expression	3
Indomethacin	increases expression, affects cotreatment, decreases reaction	3
Tamoxifen	affects expression, affects cotreatment, increases expression, decreases expression	3
Triglycerides	affects abundance, decreases expression, increases abundance, increases hydrolysis, increases uptake (+1 more)	3
triphenyl phosphate	affects cotreatment, increases expression	2
tributyltin	decreases reaction, increases expression	2
sodium arsenite	affects splicing, decreases expression	2
cordycepin	affects cotreatment, decreases reaction, increases expression	2
perfluorooctane sulfonic acid	affects expression, increases expression	2
Arsenic Trioxide	decreases expression	2
Fulvestrant	affects cotreatment, affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Estrogens	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Fenofibrate	increases activity, increases expression, increases reaction	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, increases expression	2

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015042	Binding	Inhibition of lipoprotein lipase activity assessed as release of free fatty acid from hydrolysis of VLDL by cell based assay	Design, synthesis, and biological evaluation of (2R,alphaS)-3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol as potent and orally active cholesteryl ester transfer protein inhibitor. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 induced pluripotent stem cell, 1 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1MV	AHQUi001-A-1	Induced pluripotent stem cell	Male
CVCL_A8NH	SDQLCHi042-A	Induced pluripotent stem cell	Male
CVCL_B1W3	Abcam HeLa LPL KO	Cancer cell line	Female
CVCL_F1YE	HK-2 LPL(p.464K_del)	Transformed cell line	Male
CVCL_YK97	AHQUi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

258 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00754039	PHASE4	COMPLETED	Study to Compare Welchol and TriCor to TriCor Alone in Patients With High Cholesterol
NCT00246636	PHASE4	COMPLETED	Evaluation of Efficacy and Safety of Omacor (Omega-3-acid Ethyl Esters) as Add-on Therapy in Hypertriglyceridemic Subjects Treated With Antara (Fenofibrate) Followed by an 8-week Extension
NCT00286234	PHASE4	COMPLETED	Niacin, N-3 Fatty Acids and Insulin Resistance
NCT00346697	PHASE4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00397358	PHASE4	WITHDRAWN	Effect of Extraneal (Icodextrin)on Triglyceride Levels in PD Patients
NCT00473655	PHASE4	COMPLETED	Effect of Rosuvastatin on Triglyceride Levels in Mexican Hypertriglyceridemic Patients
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00745407	PHASE4	COMPLETED	Effects of Fenofibrate on Adipocytokine Levels In Hypertriglyceridemic Patients
NCT00758927	PHASE4	UNKNOWN	The Effects of Omega-3 Fatty Acid (OMACOR) on the Low-density Lipoprotein (LDL) Sub-fraction in Type 2 Diabetic Patients
NCT00891293	PHASE4	COMPLETED	A Second Open-Label Extension of a Double-Blind, Parallel, Phase IV Study to Assess the Efficacy and Safety of Adjunctive Lovaza® (Formerly Known as Omacor®) Therapy in Hypertriglyceridemic Subjects Treated With Antara™
NCT00931879	PHASE4	COMPLETED	Lovaza® and Microvascular Function in Type 2 Diabetes
NCT00934219	PHASE4	UNKNOWN	Triglyceride Lowering Study
NCT01003847	PHASE4	COMPLETED	Differential Metabolic Effects of Fenofibrate and Fatty Acid
NCT01010399	PHASE4	COMPLETED	Boosted Lexiva With Lovaza Adjunctive Therapy in Hypertriglyceridemic, HIV-Infected Subjects
NCT01180764	PHASE4	WITHDRAWN	Effects of Lovaza on High Density Lipoprotein (HDL) Composition and Function in Hypertriglyceridemia
NCT01462877	PHASE4	COMPLETED	A Study to Evaluate Fenofibrate Combination With Statin in Chinese Patients With Dyslipidemic
NCT01480687	PHASE4	UNKNOWN	Fish Oil Supplementation and Vascular Function in Hypertensive Patients With Hypertriglyceridemia
NCT01527747	PHASE4	SUSPENDED	Effects of DPP-4 Inhibition on Triglycerides
NCT01569724	PHASE4	COMPLETED	Carbohydrate Metabolism Disorder Frequency in Hypertriglyceridemia Induced by Bexarotene of Cutaneous T Cell Lymphoma
NCT01625442	PHASE4	COMPLETED	Crocus Sativus (Saffron) and Berberis Vulgaris (Barberry Fruit) in Metabolic Syndrome
NCT01660932	PHASE4	COMPLETED	Vascular and Metabolic Effects of Omega-3 Fatty Acids
NCT01666041	PHASE4	COMPLETED	Vascular and Metabolic Effects of Fenofibrate/Omega vs Fenofibrate
NCT02015988	PHASE4	UNKNOWN	Simvastatin and Fenofibrate vs Simvastatin Alone in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome
NCT02926027	PHASE4	COMPLETED	Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy
NCT03120299	PHASE4	COMPLETED	The Effect of Omega-3 FA on Hypertriglyceridemia in Patients With T2DM(OCEAN)
NCT03342807	PHASE4	UNKNOWN	Intravenous Administration of Insulin and Plasma Exchange on Triglyceride Levels in Early Stage of Hypertriglyceridemia-induced Pancreatitis
NCT03501680	PHASE4	UNKNOWN	Intensive Insulin for Severe/Moderate Hypertriglyceridemia Pancreatitis.
NCT05487833	PHASE4	UNKNOWN	Insulin and Standard Management in Hypertriglyceridemic Acute Pancreatitis
NCT06129526	PHASE4	UNKNOWN	Study of the Efficacy and Safety of EPA in Patients With Type-2 Diabetes
NCT01514461	PHASE3	COMPLETED	A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
NCT01589237	PHASE3	TERMINATED	Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.
NCT02211209	PHASE3	COMPLETED	The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
NCT02658175	PHASE3	COMPLETED	The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome
NCT04568434	PHASE3	COMPLETED	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
NCT05130450	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)
NCT05185843	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
NCT05902598	PHASE3	COMPLETED	A Phase 3 Study of ARO-APOC3 / VSA001 / SAR449124 (Plozasiran) in Chinese Adults With Familial Chylomicronemia Syndrome
NCT02035215	PHASE3	UNKNOWN	Phase 3 Study to Evaluate the Efficacy and Safety of Omega-3-acids Ethylesters 90 in Type Ⅱb Hyperlipidemia
NCT00092560	PHASE3	COMPLETED	Two Investigational Drugs in Patients With Mixed Hyperlipidemia (0653-036)
NCT00092573	PHASE3	COMPLETED	Study of Ezetimibe and Fenofibrate in Patients With Mixed Hyperlipidemia (0653-036)(COMPLETED)