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 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 932 total — 88 pathogenic, 63 likely-pathogenic (top 3% of genes corpus-wide)
• GTEx eGene: eQTL in 23 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 23
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_000237
• Interaction hub: 2,128 STRING partners (top 6% of genes corpus-wide)

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: 17 — 11 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000650287

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 1, TSL 4: 5

ENST00000650287, ENST00000519773, ENST00000520959, ENST00000521994, ENST00000522701, ENST00000523696, ENST00000524029, ENST00000650478, ENST00000900196, ENST00000965928, ENST00000965929, ENST00000965930, ENST00000965931, ENST00000965932, ENST00001019198, ENST00001102208, ENST00001133289

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.

Highest expression (Bgee): olfactory bulb, trigeminal ganglion, dorsal root ganglion, heart right ventricle, ventricle myocardium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LPL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.3e-16	+0.69	8:20075352:C:T
Nerve Tibial	eqtl	2.2e-15	+0.20	8:19967156:C:T
Lung	eqtl	4.9e-14	+0.37	8:20076794:A:G
Heart Atrial Appendage	sqtl	1.3e-10	-0.62	8:19965319:G:A
Adipose Subcutaneous	eqtl	1.3e-07	+0.11	8:19967156:C:T
Spleen	eqtl	1.4e-05	+0.75	8:19982897:G:C
Cells Cultured fibroblasts	eqtl	9.4e-05	+0.56	8:20119800:C:G
Thyroid	eqtl	1.0e-04	+0.23	8:19958045:A:G
Lung	sqtl	1.4e-04	-0.28	8:19958727:A:C
Brain Nucleus accumbens basal ganglia	sqtl	1.6e-04	-0.79	8:19965319:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.6e-04	+0.18	8:19977539:A:T
Esophagus Muscularis	eqtl	2.5e-04	+0.29	8:19940405:G:T
Brain Anterior cingulate cortex BA24	eqtl	2.9e-04	-0.26	8:19889987:G:A
Brain Caudate basal ganglia	sqtl	7.0e-04	-0.64	8:19965319:G:A
Brain Cerebellum	eqtl	9.2e-04	-0.17	8:20073281:A:C
Testis	eqtl	3.5e-03	+0.21	8:19967156:C:T
Nerve Tibial	sqtl	3.7e-03	+0.64	8:18978016:C:T
Skin Sun Exposed Lower leg	eqtl	5.6e-03	-0.16	8:19555994:T:C
Brain Putamen basal ganglia	sqtl	7.5e-03	-0.60	8:19965319:G:A
Brain Cerebellar Hemisphere	eqtl	9.5e-03	-0.42	8:19902406:C:T

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

showing 100 of 290 tissues 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
skin of hip	UBERON:0001554	97.01	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.00	gold quality
gluteal muscle	UBERON:0002000	96.92	gold quality
biceps brachii	UBERON:0001507	96.90	gold quality
vena cava	UBERON:0004087	96.34	gold quality
putamen	UBERON:0001874	96.26	gold quality
heart	UBERON:0000948	96.20	gold quality
thoracic mammary gland	UBERON:0005200	96.14	gold quality
lung	UBERON:0002048	96.04	gold quality
caudate nucleus	UBERON:0001873	96.02	gold quality
mammary gland	UBERON:0001911	96.01	gold quality
seminal vesicle	UBERON:0000998	95.99	gold quality
upper lobe of lung	UBERON:0008948	95.94	gold quality
quadriceps femoris	UBERON:0001377	95.84	gold quality
upper lobe of left lung	UBERON:0008952	95.83	gold quality
vastus lateralis	UBERON:0001379	95.76	gold quality
lateral globus pallidus	UBERON:0002476	95.63	gold quality
mammary duct	UBERON:0001765	95.59	gold quality
skeletal muscle tissue	UBERON:0001134	95.49	gold quality
tibialis anterior	UBERON:0001385	95.44	gold quality
metanephric glomerulus	UBERON:0004736	95.33	gold quality
renal glomerulus	UBERON:0000074	95.18	gold quality
cerebellar vermis	UBERON:0004720	95.09	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.01	gold quality
muscle organ	UBERON:0001630	94.57	gold quality
epithelium of mammary gland	UBERON:0003244	94.50	gold quality
nucleus accumbens	UBERON:0001882	94.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.38	gold quality
gastrocnemius	UBERON:0001388	94.26	gold quality
muscle tissue	UBERON:0002385	94.10	gold quality
muscle of leg	UBERON:0001383	94.09	gold quality
middle temporal gyrus	UBERON:0002771	93.92	gold quality
parotid gland	UBERON:0001831	93.87	gold quality
cardiac atrium	UBERON:0002081	93.54	gold quality
endothelial cell	CL:0000115	93.35	gold quality
right atrium auricular region	UBERON:0006631	93.32	gold quality
triceps brachii	UBERON:0001509	93.30	gold quality
pleura	UBERON:0000977	92.54	gold quality
paraflocculus	UBERON:0005351	92.48	gold quality
layer of synovial tissue	UBERON:0007616	91.62	gold quality
pigmented layer of retina	UBERON:0001782	91.28	gold quality
sperm	CL:0000019	90.96	gold quality
renal medulla	UBERON:0000362	90.57	gold quality
cartilage tissue	UBERON:0002418	90.28	gold quality
choroid plexus epithelium	UBERON:0003911	90.25	gold quality
male germ cell	CL:0000015	89.92	gold quality
tongue	UBERON:0001723	89.80	gold quality
parietal pleura	UBERON:0002400	89.26	gold quality
medial globus pallidus	UBERON:0002477	88.88	gold quality
globus pallidus	UBERON:0001875	88.73	gold quality
kidney epithelium	UBERON:0004819	88.73	gold quality
left coronary artery	UBERON:0001626	88.64	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.61	gold quality
superficial temporal artery	UBERON:0001614	88.16	gold quality
coronary artery	UBERON:0001621	87.97	gold quality
amniotic fluid	UBERON:0000173	87.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.77	gold quality
mucosa of stomach	UBERON:0001199	86.61	gold quality
cortex of kidney	UBERON:0001225	86.58	gold quality
cranial nerve II	UBERON:0000941	85.80	gold quality
cerebellum	UBERON:0002037	85.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.27	gold quality
decidua	UBERON:0002450	85.20	gold quality
calcaneal tendon	UBERON:0003701	85.09	gold quality
metanephros	UBERON:0000081	85.05	gold quality
cerebellar cortex	UBERON:0002129	84.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.91	gold quality
cerebellar hemisphere	UBERON:0002245	84.78	gold quality
lower esophagus	UBERON:0013473	84.77	gold quality
telencephalon	UBERON:0001893	84.46	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Adipose tissue	tissue	880.1
Heart muscle	tissue	327.9
Parathyroid gland	tissue	170.5
Tongue	tissue	118.8
Putamen	tissue	101.9
Basal ganglia	tissue	82.5
Breast	tissue	78.5
Spinal cord	tissue	74.2
Nucleus accumbens	tissue	64.8
Seminal vesicle	tissue	61.0
Lung	tissue	58.6
Skeletal muscle	tissue	51.2
Ventral forebrain	tissue	46.6
Caudate putamen	tissue	45.3
Septum	tissue	24.7
Salivary gland	tissue	22.9
Substantia nigra	tissue	20.0
Kidney	tissue	17.9
Hippocampus	tissue	16.3
Adrenal gland	tissue	15.0
Choroid plexus	tissue	14.3
Placenta	tissue	13.8
Olfactory bulb	tissue	12.8
Retina	tissue	10.3
Medulla oblongata	tissue	10.1
Postcentral gyrus	tissue	10.1
Thyroid gland	tissue	9.9
Thalamus	tissue	9.4
Superior colliculi	tissue	9.2
Colon	tissue	9.0
Cerebral cortex	tissue	8.7
Insular cortex	tissue	8.7
Appendix	tissue	8.6
Midbrain	tissue	8.5
Motor cortex	tissue	8.4
Ovary	tissue	8.2
Occipital cortex	tissue	8.2
Gallbladder	tissue	8.1
Periaqueductal gray	tissue	8.1
Retrosplenial cortex	tissue	8.1
Amygdala	tissue	8.0
Retrosplenial and cingulate cortex	tissue	8.0
Lymph node	tissue	7.9
Somatosensory cortex	tissue	7.9
Prefrontal cortex	tissue	7.8
Pons	tissue	7.8
Temporal cortex	tissue	7.8
Frontal cortex	tissue	7.7
Hippocampal formation	tissue	7.5
Entorhinal cortex	tissue	7.5
Locus coeruleus	tissue	6.3
Pancreas	tissue	6.0
Cerebellum	tissue	5.9
Corpus callosum	tissue	5.8
Hypothalamus	tissue	5.7
Rectum	tissue	5.5
Thymus	tissue	4.0
Smooth muscle	tissue	3.8
Endometrium 1	tissue	3.5
Pituitary gland	tissue	3.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Caudate nucleus (101.8), Dorsal spinal cord (74.2), Nucleus basalis of Meynert (55.5), Blood vessel (50.2), Cerebellar cortex (38.0).

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)

Targeting LPL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 97 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.12e-12, LOEUF 1.07, missense Z -0.359 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000650287 — one region, missense o/e 1.09.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96820) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 41 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating triglyceride level	4
increased circulating VLDL triglyceride level	3
decreased circulating HDL cholesterol level	2
abnormal lipid homeostasis	2
increased circulating cholesterol level	2
neonatal lethality, complete penetrance	2
increased cardiac muscle cell glucose uptake	2
abnormal adipose tissue morphology	1
decreased circulating LDL cholesterol level	1
abnormal liver morphology	1
abnormal skeletal muscle morphology	1
atelectasis	1
increased body weight	1
abnormal cardiovascular system physiology	1
abnormal lipid level	1
hyperlipidemia	1
increased circulating HDL cholesterol level	1
cyanosis	1
abnormal glucose homeostasis	1
abnormal pulmonary alveolus morphology	1
cardiac fibrosis	1
abnormal capillary morphology	1
pallor	1
increased left ventricle diastolic pressure	1
increased left ventricle systolic pressure	1

+16 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Vespa affinis	P0DMB4	100.0%	Diamond
Bos taurus	P11151	99.4%	Diamond
Papio anubis	P49060	99.4%	Diamond
Ovis aries	Q29524	99.4%	Diamond
Pongo abelii	Q5RBQ5	98.2%	Diamond
Neogale vison	O46647	96.2%	Diamond
Felis catus	P55031	96.2%	Diamond
Vespa velutina	C0HLL3	95.7%	Diamond
Vespula vulgaris	P49369	95.0%	Diamond
Vespula maculifrons	P51528	95.0%	Diamond
Vespula germanica	Q3ZU95	94.7%	Diamond
Sus scrofa	P49923	92.9%	Diamond
Vespa tropica	P0DPT0	92.4%	Diamond
Xenopus tropicalis	Q5XGE9	92.0%	Diamond
Xenopus laevis	Q6PA23	92.0%	Diamond
Vespa magnifica	P0CH47	91.4%	Diamond
Cavia porcellus	P11153	88.3%	Diamond
Ictidomys tridecemlineatus	O88354	85.8%	Diamond
Canis lupus familiaris	P06857	85.2%	Diamond
Polistes annularis	Q9U6W0	84.7%	Diamond
Equus caballus	P29183	83.6%	Diamond
Myocastor coypus	Q64425	82.3%	Diamond
Oryctolagus cuniculus	Q9BDJ4	82.3%	Diamond
Dolichovespula maculata	P53357	80.9%	Diamond
Gallus gallus	P11602	77.4%	Diamond
Crotalus adamanteus	J3RZ81	68.4%	Diamond
Vespula squamosa	P0CH86	68.4%	Diamond
Ceratitis capitata	P27878	56.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SLC18A1	protein-coding	6570
INTS10	protein-coding	55174
ATP6V1B2	protein-coding	526

Protein

Protein identifiers

Lipoprotein lipase — P06858 (reviewed: P06858)

Alternative names: Phospholipase A1

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

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)

• 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 (163 total): sequence variant 75, strand 26, mutagenesis site 17, helix 15, 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 by resolution:

PDB	Title	Method	Resolution (Å)
6OAU	Apo Structure of WT Lipoprotein Lipase in Complex with GPIHBP1 Mutant N78D N82D produced …	X-RAY DIFFRACTION	2.48
6E7K	Structure of the lipoprotein lipase GPIHBP1 complex that mediates plasma triglyceride …	X-RAY DIFFRACTION	2.8
6WN4	Structural basis for the binding of monoclonal antibody 5D2 to the tryptophan-rich …	X-RAY DIFFRACTION	2.8
6OB0	Compound 2 bound structure of WT Lipoprotein Lipase in Complex with GPIHBP1 Mutant N78D …	X-RAY DIFFRACTION	2.81
6OAZ	Apo Structure of WT Lipoprotein Lipase in Complex with GPIHBP1 Mutant N78D N82D produced …	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 antibodies co-crystallized with this protein: 6WN4

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of lipid/glycolipid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IF approved

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)

Position	Role
268	charge relay system
159	nucleophile
183	charge relay system

Ligand- & substrate-binding residues (4)

Position	Role
194	Ca(2+)
197	Ca(2+)
199	Ca(2+)
202	Ca(2+)

Post-translational modifications (3)

Type	Positions
3’-nitrotyrosine	121, 191, 343

Disulfide bonds (5)

Type	Positions
Disulfide bond	54–67, 243–266, 291–310, 302–305, 445–465

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	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-421.
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

4 curated (TAS) of 20; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

20 pathways:

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

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 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), positive regulation of triglyceride transport (GO:1905885)

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 (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), very-low-density lipoprotein particle (GO:0034361), chylomicron (GO:0042627)

Reactome top-level categories

15 top-level categories:

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

showing 60 of 62 GO namespaces:

Category	Terms
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
cellular anatomical structure	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 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
plasma lipoprotein particle remodeling	1
plasma lipoprotein particle clearance	1
sterol homeostasis	1
triacylglycerol lipase activity	1
phospholipase activity	1
lipase activity	1
carboxylic ester hydrolase activity	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
A1-type glycerophospholipase activity	1
identical protein binding	1
protein dimerization activity	1
proteoglycan binding	1
protein-macromolecule adaptor activity	1
protein-lipid complex binding	1
binding	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 53 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
cholesterol homeostasis	BP	mutant phenotype
chylomicron remodeling	BP	mutant phenotype
fatty acid biosynthetic process	BP	direct assay
fatty acid metabolic process	BP	direct assay
low-density lipoprotein particle mediated signaling	BP	mutant phenotype
positive regulation of adipose tissue development	BP	mutant phenotype
positive regulation of chemokine production	BP	mutant phenotype
positive regulation of cholesterol storage	BP	mutant phenotype
positive regulation of fat cell differentiation	BP	mutant phenotype
positive regulation of inflammatory response	BP	mutant phenotype
positive regulation of macrophage derived foam cell differentiation	BP	mutant phenotype
triglyceride catabolic process	BP	direct assay
triglyceride homeostasis	BP	genetic interaction
triglyceride metabolic process	BP	mutant phenotype
very-low-density lipoprotein particle remodeling	BP	direct assay
apolipoprotein binding	MF	physical interaction
calcium ion binding	MF	direct assay
glycerophospholipid phospholipase A1 activity	MF	direct assay
heparan sulfate proteoglycan binding	MF	mutant phenotype
heparin binding	MF	direct assay
lipoprotein lipase activity	MF	direct assay
lipoprotein particle binding	MF	direct assay
protein homodimerization activity	MF	direct assay
signaling receptor binding	MF	physical interaction
triacylglycerol lipase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,128 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPL	APOC2	P02655	933
LPL	APOC3	P02656	923
LPL	LMF1	Q96S06	917
LPL	GPIHBP1	Q8IV16	914
LPL	CETP	P11597	886
LPL	LIPE	Q05469	882
LPL	FABP4	P15090	871
LPL	APOA5	Q6Q788	871
LPL	APOB	P04114	866
LPL	PPARG	P37231	862
LPL	ANGPTL3	Q9Y5C1	862
LPL	ANGPTL4	Q9BY76	857
LPL	APOE	P02649	845
LPL	APOA1	P02647	840
LPL	INS	P01308	836

IntAct

Human interaction partners of LPL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

26 partners by confidence:

Partner	Interaction type	MIscore	Records
GPIHBP1	direct interaction	0.740	7
CCDC26	physical association	0.560	3
EIF2B4	physical association	0.560	3
NME4	physical association	0.560	3
NPHP1	physical association	0.560	3
PRMT5	physical association	0.560	3
PRRG2	physical association	0.560	3
PSMD9	physical association	0.560	3
SLFN12	physical association	0.560	3
SNX12	physical association	0.560	3
TGOLN2	physical association	0.560	3
TMEM185A	physical association	0.560	3
VKORC1L1	physical association	0.560	3
ANGPTL3	direct interaction	0.440	1
ANGPTL4	direct interaction	0.440	1
APOA5	direct interaction	0.440	1
SORT1	direct interaction	0.440	1
CCND1	physical association	0.370	1
MTRFR	association	0.350	1
ASCC2	physical association	0.000	1
CEP126	physical association	0.000	1
COPS6	physical association	0.000	1
LUC7L2	physical association	0.000	1
PTPN4	physical association	0.000	1
RPL18A	physical association	0.000	1
UBE2Z	physical association	0.000	1

BioGRID (42 interactions; top human partners by supporting records): LRP1 (Reconstituted Complex; 3 records), APP (Reconstituted Complex), ASCC2 (Two-hybrid), C12orf65 (Affinity Capture-MS), CALCOCO2 (Proximity Label-MS), CALR (Affinity Capture-Western), CCND1 (Two-hybrid), COPS6 (Two-hybrid), CPVL (Affinity Capture-MS), CUL3 (Affinity Capture-MS), DCX (Affinity Capture-MS), DPP4 (Affinity Capture-MS), E2F4 (Affinity Capture-MS), EEF2KMT (Affinity Capture-MS), EMD (Two-hybrid)

SIGNOR signaling

showing 13 of 15 signaling 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

Genetic variants

Variant evidence for LPL: 932 ClinVar records (151 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 315 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	88
Likely pathogenic	63
Uncertain significance	277
Likely benign	362
Benign	54

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 151 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1527	NM_000237.3(LPL):c.701C>T (p.Pro234Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
1541	NM_000237.3(LPL):c.272G>A (p.Trp91Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
1535	NM_000237.3(LPL):c.249+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1556	NM_000237.3(LPL):c.987C>A (p.Tyr329Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
851236	NM_000237.3(LPL):c.836T>G (p.Leu279Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1066636	NM_000237.3(LPL):c.805G>A (p.Glu269Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1452072	NM_000237.3(LPL):c.590G>T (p.Arg197Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1537	NM_000237.3(LPL):c.1227G>A (p.Trp409Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
995957	NM_000237.3(LPL):c.765_766del (p.Gly256fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1693264	NM_000237.3(LPL):c.1019-2A>T	Pathogenic	criteria provided, multiple submitters, no conflicts	3
950321	NM_000237.3(LPL):c.94_98del (p.Arg32fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1401888	NM_000237.3(LPL):c.566_567del (p.Asn188_Phe189insTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2484764	NM_000237.3(LPL):c.899_921dup (p.Asn308delinsGlySerAlaTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2582665	NM_000237.3(LPL):c.1014C>A (p.Tyr338Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2735125	NM_000237.3(LPL):c.440_443del (p.Asn147fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore LPL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 744):

Position(s)	Effect	Δscore	Sites
8:19948178–19948179	acceptor_loss	1.0000	5
8:19948341–19948342	donor_loss	1.0000	5
8:19951949	donor_loss	1.0000	2
8:19953422–19953423	donor_loss	1.0000	5
8:19954118–19954119	acceptor_gain	1.0000	2
8:19954118–19954119	acceptor_loss	1.0000	4
8:19954354–19954355	donor_loss	1.0000	5
8:19961069	donor_gain	1.0000
8:19939529–19939530	donor_loss	0.9900	5
8:19948179	acceptor_loss	0.9900

AlphaMissense

1,221 missense substitutions predicted likely pathogenic (of 3,139 scored), across 284 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H268	8	0.998	0.999
D183	8	0.997	0.999
S159	8	0.994	0.999
H210	8	0.993	0.999
D231	8	0.990	0.998
H80	8	0.981	0.997
D207	8	0.969	0.991
H163	8	0.968	0.994
D202	8	0.965	0.982
D277	8	0.964	0.996
F189	8	0.962	0.999
F297	8	0.955	0.997
N235	8	0.944	0.999
F275	8	0.931	0.997
F462	8	0.926	0.992
H154	8	0.917	0.993
F444	8	0.911	0.994
F205	8	0.905	0.988
H342	8	0.905	0.987
D134	8	0.888	0.964

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.81e-06
Kidney Renal Clear Cell Carcinoma (validation)	favorable	5.95e-05
Stomach Adenocarcinoma (TCGA)	unfavorable	0.000121

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
familial lipoprotein lipase deficiency	Definitive	Autosomal recessive	6
hyperlipidemia, familial combined, LPL related	Strong	Autosomal dominant	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Familial Chylomicronaemia Syndrome	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Severe hypertriglyceridaemia	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): familial lipoprotein lipase deficiency (MONDO:0009387), lipase deficiency, combined (MONDO:0009527), hyperlipidemia, familial combined, LPL related (MONDO:0007759)

Orphanet (3): Familial lipoprotein lipase deficiency (Orphanet:309015), Familial chylomicronemia syndrome (Orphanet:444490), Familial lipase maturation factor 1 deficiency (Orphanet:535453)

HPO phenotypes

23 phenotypes (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	Elevated circulating LDL-C concentration
HP:0003362	Elevated circulating VLDL-C 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

GWAS associations

showing 30 of 315 associations:

Study	Trait	p-value
GCST010173_25	Triglyceride levels	0.000000e+00
GCST010241_208	Apolipoprotein A1 levels	0.000000e+00
GCST010242_120	HDL cholesterol levels	0.000000e+00
GCST010244_325	Triglyceride levels	0.000000e+00
GCST008075_64	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6e-299
GCST008084_3	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3e-225
GCST004237_3	Triglyceride levels	5e-217
GCST008075_205	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8e-216
GCST008083_2	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1e-215
GCST008083_157	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	9e-203
GCST008074_26	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4e-200
GCST002216_15	Triglycerides	2e-199
GCST008074_92	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2e-198
GCST011345_11	Triglyceride levels	1e-196
GCST008087_56	Triglyceride levels in current drinkers	3e-195
GCST004232_46	HDL cholesterol levels	4e-176
GCST008085_164	HDL cholesterol levels in current drinkers	4e-166
GCST008076_55	Triglyceride levels	6e-158
GCST006003_16	Triglyceride levels	1e-154
GCST002223_20	HDL cholesterol	1e-149
GCST010242_57	HDL cholesterol levels	5e-144
GCST009602_59	Metabolic syndrome	1e-138
GCST008083_99	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5e-137
GCST008074_69	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9e-136
GCST008070_52	HDL cholesterol levels	4e-131
GCST009368_14	HDL cholesterol levels x long total sleep time interaction (2df test)	7e-126
GCST010244_335	Triglyceride levels	4e-120
GCST000758_28	Triglycerides	2e-115
GCST011348_16	High density lipoprotein cholesterol levels	2e-115
GCST010244_338	Triglyceride levels	7e-115

EFO canonical traits (from GWAS)

29 canonical traits:

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

2 disease descriptors:

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
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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,508 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL175247	ORLISTAT	4	38,508

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

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

PharmGKB variants

2 variants:

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

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs320	fenofibrate	Efficacy	Genotype GG is associated with decreased response to fenofibrate in people with Hypertriglyceridemia as compared to genotypes GT + TT.	PMID:19207029
rs328	pioglitazone	Efficacy	Genotypes CG + GG are associated with decreased response rate after 10 weeks of pioglitazone treatment when treated with pioglitazone in people with Diabetes Mellitus, Type 2 as compared to genotype CC.	PMID:17394430
rs328	pravastatin	Efficacy	Genotype GG is associated with increased response to pravastatin as compared to genotypes CC + CG.	PMID:16103896

Binding affinities (BindingDB)

45 measured of 49 human assays (51 total across all organisms); most potent 45 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3093304	IC50	25 nM
CHEMBL4212095	IC50	61 nM
CHEMBL3093396	IC50	88 nM
(4-nonylphenyl)boranediol	IC50	100 nM
CHEMBL3093392	IC50	110 nM
CHEMBL3093394	IC50	120 nM
CHEMBL3093393	IC50	130 nM
CHEMBL3093307	IC50	131 nM
CHEMBL3093309	IC50	156 nM
CHEMBL4471545	IC50	170 nM
CHEMBL3093302	IC50	184 nM
CHEMBL1952298	IC50	200 nM
CHEMBL3093395	IC50	214 nM
CHEMBL3093308	IC50	236 nM
CHEMBL3093306	IC50	236 nM
CHEMBL3093303	IC50	259 nM
CHEMBL3093391	IC50	366 nM
CHEMBL3093305	IC50	372 nM
CHEMBL3093398	IC50	499 nM
CHEMBL3093399	IC50	551 nM
3-(3-Benzyloxy-phenyl)-5-ethoxy-3H-[1,3,4]oxadiazol-2-one	IC50	750 nM
CHEMBL1952296	IC50	1000 nM
CHEMBL1949700	IC50	1000 nM
CHEMBL1952307	IC50	1000 nM
CHEMBL3093405	IC50	1010 nM
CHEMBL1952303	IC50	1100 nM
CHEMBL1952304	IC50	1100 nM
CHEMBL1952308	IC50	1100 nM
CHEMBL1952309	IC50	1300 nM
CHEMBL1952312	IC50	1300 nM
CHEMBL1952305	IC50	1400 nM
CHEMBL1952310	IC50	1600 nM
CHEMBL1952297	IC50	1700 nM
CHEMBL1952313	IC50	1700 nM
CHEMBL4207216	IC50	1760 nM
CHEMBL1952295	IC50	2000 nM
CHEMBL1952300	IC50	2800 nM
CHEMBL1952311	IC50	2800 nM
CHEMBL1952302	IC50	5000 nM
CHEMBL1952294	IC50	11000 nM
CHEMBL1952301	IC50	11000 nM
CHEMBL1952299	IC50	12800 nM
(S)-4-isopropyl-3-methyl-2-(3-methylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	17000 nM
CHEMBL1952306	IC50	35000 nM
CHEMBL1952314	IC50	300000 nM

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	affects expression, affects cotreatment, increases expression, affects methylation, decreases expression (+2 more)	10
Rosiglitazone	affects transport, affects cotreatment, increases expression, increases reaction, decreases reaction	10
Dexamethasone	decreases expression, decreases reaction, increases reaction, affects expression, affects cotreatment (+1 more)	10
1-Methyl-3-isobutylxanthine	increases expression, decreases reaction, decreases expression, increases reaction, affects expression (+1 more)	10
bisphenol S	decreases expression, affects cotreatment, increases expression	6
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Orlistat	increases uptake, increases activity, decreases activity, decreases reaction, increases hydrolysis	4
Estradiol	increases expression, affects cotreatment, decreases expression, affects expression, affects binding	4
bisphenol F	increases expression, affects cotreatment	3
very low density lipoprotein triglyceride	increases hydrolysis, increases abundance, decreases reaction, increases activity, affects reaction (+1 more)	3
T 0070907	increases expression, affects cotreatment, decreases expression, decreases reaction	3
Troglitazone	affects cotreatment, increases expression, increases metabolic processing	3
Bezafibrate	increases activity	3
Clofibrate	increases activity, increases expression	3
Indomethacin	decreases reaction, increases expression, affects cotreatment	3
Tamoxifen	affects expression, affects cotreatment, increases expression, decreases expression	3
Triglycerides	increases hydrolysis, increases uptake, decreases reaction, affects abundance, decreases expression (+1 more)	3
triphenyl phosphate	affects cotreatment, increases expression	2
tributyltin	decreases reaction, increases expression	2
sodium arsenite	affects splicing, decreases expression	2
cordycepin	increases expression, affects cotreatment, decreases reaction	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	decreases expression, affects methylation	2
Estrogens	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Fenofibrate	increases activity, increases expression, increases reaction	2
Tetrachlorodibenzodioxin	increases expression, decreases 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 262 trials:

NCT	Phase	Status	Title
NCT00754039	Phase 4	COMPLETED	Study to Compare Welchol and TriCor to TriCor Alone in Patients With High Cholesterol
NCT00246636	Phase 4	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	Phase 4	COMPLETED	Niacin, N-3 Fatty Acids and Insulin Resistance
NCT00346697	Phase 4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00397358	Phase 4	WITHDRAWN	Effect of Extraneal (Icodextrin)on Triglyceride Levels in PD Patients
NCT00473655	Phase 4	COMPLETED	Effect of Rosuvastatin on Triglyceride Levels in Mexican Hypertriglyceridemic Patients
NCT00632840	Phase 4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00745407	Phase 4	COMPLETED	Effects of Fenofibrate on Adipocytokine Levels In Hypertriglyceridemic Patients
NCT00758927	Phase 4	UNKNOWN	The Effects of Omega-3 Fatty Acid (OMACOR) on the Low-density Lipoprotein (LDL) Sub-fraction in Type 2 Diabetic Patients
NCT00891293	Phase 4	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	Phase 4	COMPLETED	Lovaza® and Microvascular Function in Type 2 Diabetes
NCT00934219	Phase 4	UNKNOWN	Triglyceride Lowering Study
NCT01003847	Phase 4	COMPLETED	Differential Metabolic Effects of Fenofibrate and Fatty Acid
NCT01010399	Phase 4	COMPLETED	Boosted Lexiva With Lovaza Adjunctive Therapy in Hypertriglyceridemic, HIV-Infected Subjects
NCT01180764	Phase 4	WITHDRAWN	Effects of Lovaza on High Density Lipoprotein (HDL) Composition and Function in Hypertriglyceridemia
NCT01462877	Phase 4	COMPLETED	A Study to Evaluate Fenofibrate Combination With Statin in Chinese Patients With Dyslipidemic
NCT01480687	Phase 4	UNKNOWN	Fish Oil Supplementation and Vascular Function in Hypertensive Patients With Hypertriglyceridemia
NCT01527747	Phase 4	SUSPENDED	Effects of DPP-4 Inhibition on Triglycerides
NCT01569724	Phase 4	COMPLETED	Carbohydrate Metabolism Disorder Frequency in Hypertriglyceridemia Induced by Bexarotene of Cutaneous T Cell Lymphoma
NCT01625442	Phase 4	COMPLETED	Crocus Sativus (Saffron) and Berberis Vulgaris (Barberry Fruit) in Metabolic Syndrome
NCT01660932	Phase 4	COMPLETED	Vascular and Metabolic Effects of Omega-3 Fatty Acids
NCT01666041	Phase 4	COMPLETED	Vascular and Metabolic Effects of Fenofibrate/Omega vs Fenofibrate
NCT02015988	Phase 4	UNKNOWN	Simvastatin and Fenofibrate vs Simvastatin Alone in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome
NCT02926027	Phase 4	COMPLETED	Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy
NCT03120299	Phase 4	COMPLETED	The Effect of Omega-3 FA on Hypertriglyceridemia in Patients With T2DM(OCEAN)
NCT03342807	Phase 4	UNKNOWN	Intravenous Administration of Insulin and Plasma Exchange on Triglyceride Levels in Early Stage of Hypertriglyceridemia-induced Pancreatitis
NCT03501680	Phase 4	UNKNOWN	Intensive Insulin for Severe/Moderate Hypertriglyceridemia Pancreatitis.
NCT05487833	Phase 4	UNKNOWN	Insulin and Standard Management in Hypertriglyceridemic Acute Pancreatitis
NCT06129526	Phase 4	UNKNOWN	Study of the Efficacy and Safety of EPA in Patients With Type-2 Diabetes
NCT07617155	Phase 4	NOT_YET_RECRUITING	GLP-1 Agonists for Prevention of Recurrent Hypertriglyceridemic Acute Pancreatitis
NCT01514461	Phase 3	COMPLETED	A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
NCT01589237	Phase 3	TERMINATED	Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.
NCT02211209	Phase 3	COMPLETED	The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
NCT02658175	Phase 3	COMPLETED	The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome
NCT04568434	Phase 3	COMPLETED	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
NCT05130450	Phase 3	ACTIVE_NOT_RECRUITING	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)
NCT05185843	Phase 3	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	Phase 3	COMPLETED	A Phase 3 Study of ARO-APOC3 / VSA001 / SAR449124 (Plozasiran) in Chinese Adults With Familial Chylomicronemia Syndrome
NCT07727538	Phase 3	RECRUITING	A Study of Olezarsen for the Treatment of Familial Chylomicronemia Syndrome (FCS) in Pediatric Participants
NCT02035215	Phase 3	UNKNOWN	Phase 3 Study to Evaluate the Efficacy and Safety of Omega-3-acids Ethylesters 90 in Type Ⅱb Hyperlipidemia
NCT00092560	Phase 3	COMPLETED	Two Investigational Drugs in Patients With Mixed Hyperlipidemia (0653-036)
NCT00092573	Phase 3	COMPLETED	Study of Ezetimibe and Fenofibrate in Patients With Mixed Hyperlipidemia (0653-036)(COMPLETED)
NCT00093899	Phase 3	COMPLETED	A Study to Evaluate an Investigational Drug in Patients With Mixed Hyperlipidemia (0653A-071)(COMPLETED)
NCT00134498	Phase 3	COMPLETED	A Study Comparing The Efficacy & Safety Of Torcetrapib/Atorvastatin And Atorvastatin In Subjects With High Triglycerides
NCT00231621	Phase 3	TERMINATED	A Study on Efficacy and Safety of Topiramate in Treatment of Obese Subjects With Dyslipidemia
NCT00246701	Phase 3	COMPLETED	Evaluation of Efficacy and Safety of Combined Omacor (Omega-3-acid Ethyl Esters) and Simvastatin Therapy in Hypertriglyceridemic Subjects
NCT00435045	Phase 3	COMPLETED	Evaluation of Efficacy and Safety of Omacor, Co-Administered With Atorvastatin, in Subjects With Hypertriglyceridemia
NCT00560430	Phase 3	COMPLETED	Regulation of Inflammatory Parameters by Telmisartan in Hypertensive Patients
NCT00887653	Phase 3	COMPLETED	Changes in Lipids and Safety of Raltegravir in HIV+ Patients With Hyperlipidemia While on Current Standard Therapy
NCT00903409	Phase 3	COMPLETED	Open-Label Extension of a Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lovaza® and Simvastatin Therapy in Hypertriglyceridemic Subjects
NCT00973271	Phase 3	WITHDRAWN	Diazoxide Choline Controlled-Release Tablet (DCCR) for Very High Triglycerides
NCT01047501	Phase 3	COMPLETED	Effect of AMR101 (Ethyl Icosapentate) on Triglyceride (Tg) Levels in Patients on Statins With High Tg Levels (≥ 200 and < 500 mg/dL)
NCT01047683	Phase 3	COMPLETED	Efficacy and Safety of AMR101 (Ethyl Icosapentate) in Patients With Fasting Triglyceride (Tg) Levels ≥ 500 and ≤ 2000 mg/dL
NCT01229566	Phase 3	UNKNOWN	Efficacy Study to Treat Subjects With Severe Hypertriglyceridemia
NCT01350973	Phase 3	COMPLETED	Efficacy of TAK-085 in Participants With Hypertriglyceridemia
NCT01350999	Phase 3	COMPLETED	Long-term Efficacy and Safety Study of TAK-085 in Participants With Hypertriglyceridemia
NCT01408303	Phase 3	COMPLETED	[E]PANOVA Combined With a [S]TATIN in [P]ATIENTS With HYPERT[R]IGLYCER[I]DEMIA to Reduce Non-HDL CHOLES[T]EROL
NCT01725646	Phase 3	COMPLETED	An Efficacy and Safety Study of Omacor® in Taiwanese Hypertriglyceridemic Patients
NCT01997268	Phase 3	WITHDRAWN	The Efficacy of EPA+DHA (SC401B) for Lowering Triglyceride Levels (≥ 500 mg/dL)
NCT02009865	Phase 3	COMPLETED	Epanova® for Lowering Very High Triglycerides II (EVOLVE II)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LPL across ~30M SureChEMBL compounds — explore on Sugi Predict.