LIPE

Summary

LIPE (lipase E, hormone sensitive type, HGNC:6621) is a protein-coding gene on chromosome 19q13.2, encoding Hormone-sensitive lipase (Q05469). Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters.

The protein encoded by this gene has a long and a short form, generated by use of alternative translational start codons. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids.

Source: NCBI Gene 3991 — RefSeq curated summary.

At a glance

• Gene–disease (curated): LIPE-related familial partial lipodystrophy (Definitive, ClinGen)
• Clinical variants (ClinVar): 300 total — 3 pathogenic, 5 likely-pathogenic
• Expression (HPA): Group enriched — highest in adipose tissue, parieto-temporal junction (white matter), cerebellar white matter
• GTEx eGene: eQTL in 9 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 37
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.93 (unconstrained)
• MANE Select transcript: NM_005357
• Interaction hub: 2,022 STRING partners (top 7% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6621
Approved symbol	LIPE
Name	lipase E, hormone sensitive type
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	HSL
Ensembl gene	ENSG00000079435
Ensembl biotype	protein_coding
OMIM	151750
Entrez	3991

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000244289

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 4, TSL 5: 3

ENST00000244289, ENST00000597001, ENST00000597620, ENST00000599211, ENST00000599783, ENST00000599918, ENST00000600224, ENST00000601189, ENST00000602000

RefSeq mRNA: 10 — MANE Select: NM_005357 NM_001416100, NM_001416101, NM_001416102, NM_001416103, NM_001416104, NM_001416105, NM_001416106, NM_001416107, NM_001416108, NM_005357

CCDS: CCDS12607

Canonical transcript exons

ENST00000244289 — 10 exons

Exon	Start	End
ENSE00000709257	42406161	42406388
ENSE00000709260	42405385	42405561
ENSE00000709262	42402607	42403031
ENSE00001162583	42426267	42427388
ENSE00001194800	42401514	42402075
ENSE00003076590	42407174	42407468
ENSE00004034694	42407976	42408121
ENSE00004034696	42407606	42407791
ENSE00004034697	42408232	42408322
ENSE00004034698	42410307	42410842

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1310 / max 2297.0978, expressed in 923 samples.

Highest expression (Bgee): omental fat pad, peritoneum, C1 segment of cervical spinal cord, adipose tissue of abdominal region, subcutaneous adipose tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LIPE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	eqtl	4.4e-08	+0.46	19:42423369:T:C
Spleen	eqtl	1.8e-04	+0.49	19:42412478:G:C
Whole Blood	eqtl	2.7e-04	+0.25	19:42412478:G:C
Brain Anterior cingulate cortex BA24	eqtl	5.6e-03	+0.47	19:42394998:T:G
Brain Caudate basal ganglia	sqtl	7.7e-03	-2.34	19:43261245:C:G
Adipose Subcutaneous	sqtl	1.4e-02	-0.44	19:41443569:G:T
Breast Mammary Tissue	eqtl	1.9e-02	-0.32	19:41480535:A:G
Cells Cultured fibroblasts	eqtl	3.2e-02	+0.24	19:42249131:G:A
Artery Tibial	eqtl	3.8e-02	-0.37	19:42442175:G:C
Skin Sun Exposed Lower leg	eqtl	3.9e-02	+0.41	19:42904634:T:A
Adipose Subcutaneous	eqtl	4.5e-02	-0.08	19:43391628:G:A

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
181186	11.8181	226
181190	1.4375	689
181189	0.6774	317
181187	0.0950	36
181191	0.0685	14
181192	0.0302	9
181188	0.0043	3

Top tissues by expression

showing 100 of 276 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
omental fat pad	UBERON:0010414	98.67	gold quality
peritoneum	UBERON:0002358	98.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.87	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.63	gold quality
adipose tissue	UBERON:0001013	97.34	gold quality
spinal cord	UBERON:0002240	96.34	gold quality
connective tissue	UBERON:0002384	95.56	gold quality
pericardium	UBERON:0002407	94.94	gold quality
right testis	UBERON:0004534	94.68	gold quality
left testis	UBERON:0004533	94.59	gold quality
inferior vagus X ganglion	UBERON:0005363	93.58	silver quality
apex of heart	UBERON:0002098	93.09	gold quality
middle frontal gyrus	UBERON:0002702	93.00	gold quality
inferior olivary complex	UBERON:0002127	92.49	silver quality
olfactory bulb	UBERON:0002264	92.04	gold quality
subthalamic nucleus	UBERON:0001906	91.89	silver quality
right adrenal gland cortex	UBERON:0035827	91.40	gold quality
type B pancreatic cell	CL:0000169	91.05	gold quality
right adrenal gland	UBERON:0001233	90.99	gold quality
left adrenal gland cortex	UBERON:0035825	90.76	gold quality
left adrenal gland	UBERON:0001234	90.57	gold quality
adrenal cortex	UBERON:0001235	90.53	gold quality
testis	UBERON:0000473	90.49	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	90.36	silver quality
substantia nigra	UBERON:0002038	90.33	gold quality
midbrain	UBERON:0001891	90.28	gold quality
corpus callosum	UBERON:0002336	89.79	gold quality
heart left ventricle	UBERON:0002084	89.59	gold quality
adrenal gland	UBERON:0002369	89.52	gold quality
pons	UBERON:0000988	89.51	silver quality
cardiac ventricle	UBERON:0002082	89.51	gold quality
putamen	UBERON:0001874	89.42	gold quality
ventral tegmental area	UBERON:0002691	89.30	silver quality
substantia nigra pars reticulata	UBERON:0001966	89.19	silver quality
hindlimb stylopod muscle	UBERON:0004252	89.16	gold quality
vena cava	UBERON:0004087	88.99	silver quality
medulla oblongata	UBERON:0001896	88.94	gold quality
lateral globus pallidus	UBERON:0002476	88.70	silver quality
diaphragm	UBERON:0001103	88.42	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.36	silver quality
Ammon’s horn	UBERON:0001954	88.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.74	silver quality
prefrontal cortex	UBERON:0000451	87.62	gold quality
heart right ventricle	UBERON:0002080	87.61	silver quality
superior vestibular nucleus	UBERON:0007227	87.19	silver quality
hypothalamus	UBERON:0001898	87.09	gold quality
mammary duct	UBERON:0001765	87.02	silver quality
caudate nucleus	UBERON:0001873	86.89	gold quality
substantia nigra pars compacta	UBERON:0001965	86.80	silver quality
paraflocculus	UBERON:0005351	86.55	silver quality
Brodmann (1909) area 9	UBERON:0013540	86.54	gold quality
amygdala	UBERON:0001876	86.35	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.23	silver quality
ventricular zone	UBERON:0003053	86.15	gold quality
adrenal tissue	UBERON:0018303	86.06	gold quality
nucleus accumbens	UBERON:0001882	86.04	gold quality
layer of synovial tissue	UBERON:0007616	86.00	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.83	silver quality
vastus lateralis	UBERON:0001379	85.76	gold quality
heart	UBERON:0000948	85.70	gold quality
frontal pole	UBERON:0002795	85.69	gold quality
frontal cortex	UBERON:0001870	85.58	gold quality
cardia of stomach	UBERON:0001162	85.45	gold quality
telencephalon	UBERON:0001893	85.37	gold quality
epithelium of mammary gland	UBERON:0003244	85.17	silver quality
tibial nerve	UBERON:0001323	85.14	gold quality
central nervous system	UBERON:0001017	85.01	gold quality
forebrain	UBERON:0001890	84.84	gold quality
temporal lobe	UBERON:0001871	84.83	gold quality
gastrocnemius	UBERON:0001388	84.80	gold quality
right frontal lobe	UBERON:0002810	84.78	gold quality
left coronary artery	UBERON:0001626	84.76	gold quality
parietal lobe	UBERON:0001872	84.74	silver quality
neocortex	UBERON:0001950	84.68	gold quality
brain	UBERON:0000955	84.65	gold quality
cerebral cortex	UBERON:0000956	84.65	gold quality
coronary artery	UBERON:0001621	84.56	gold quality
postcentral gyrus	UBERON:0002581	84.54	silver quality
synovial joint	UBERON:0002217	84.09	silver quality
ganglionic eminence	UBERON:0004023	84.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.05	gold quality
muscle of leg	UBERON:0001383	84.04	gold quality
muscle organ	UBERON:0001630	83.81	gold quality
occipital lobe	UBERON:0002021	83.70	gold quality
thoracic mammary gland	UBERON:0005200	83.65	gold quality
skin of leg	UBERON:0001511	83.64	gold quality
mammary gland	UBERON:0001911	83.54	gold quality
endothelial cell	CL:0000115	83.52	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	83.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.35	gold quality
spleen	UBERON:0002106	83.32	gold quality
cerebellar cortex	UBERON:0002129	83.26	gold quality
cerebellar hemisphere	UBERON:0002245	83.22	gold quality
cerebellum	UBERON:0002037	83.19	gold quality
right atrium auricular region	UBERON:0006631	83.05	gold quality
primary visual cortex	UBERON:0002436	82.92	gold quality
cardiac atrium	UBERON:0002081	82.78	gold quality
saliva-secreting gland	UBERON:0001044	82.76	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.49

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Adipose tissue	tissue	783.5	high
Locus coeruleus	tissue	65.7
Nucleus accumbens	tissue	59.1
Hippocampus	tissue	41.9	not detected
Postcentral gyrus	tissue	31.5
Breast	tissue	25.2	high
Testis	tissue	22.1	high
Corpus callosum	tissue	22.1
Tongue	tissue	21.7
Adrenal gland	tissue	16.4	not detected
Salivary gland	tissue	16.2	not detected
Spinal cord	tissue	15.8
Heart muscle	tissue	13.4	not detected
Medulla oblongata	tissue	12.9
Choroid plexus	tissue	11.8
Skeletal muscle	tissue	10.6	not detected
Midbrain	tissue	10.5
Substantia nigra	tissue	10.2
Superior colliculi	tissue	8.6
Thalamus	tissue	8.3
Spleen	tissue	7.9	not detected
Periaqueductal gray	tissue	7.8
Pons	tissue	7.7
Ventral forebrain	tissue	7.5
Appendix	tissue	7.4	medium
Vagina	tissue	7.2	not detected
Putamen	tissue	7.1
Small intestine	tissue	7.1	medium
Pituitary gland	tissue	6.8
Lymph node	tissue	6.8	not detected
Cerebellum	tissue	6.8	not detected
Hypothalamus	tissue	6.5
Thymus	tissue	6.5
Colon	tissue	5.8	medium
Hippocampal formation	tissue	5.8
Caudate putamen	tissue	5.8
Olfactory bulb	tissue	5.5
Septum	tissue	5.4
Duodenum	tissue	5.0	medium
Bone marrow	tissue	4.7	not detected
Cerebral cortex	tissue	4.6	not detected
Somatosensory cortex	tissue	4.6
Pancreas	tissue	4.5	not detected
Parathyroid gland	tissue	4.4	not detected
Retrosplenial cortex	tissue	4.4
Occipital cortex	tissue	4.4
Esophagus	tissue	4.2	not detected
Frontal cortex	tissue	4.2
Amygdala	tissue	4.2
Insular cortex	tissue	4.2
Basal ganglia	tissue	4.1	not detected
Motor cortex	tissue	4.0
Urinary bladder	tissue	3.9	not detected
Retrosplenial and cingulate cortex	tissue	3.6
Gallbladder	tissue	3.5	not detected
Temporal cortex	tissue	3.5
Prefrontal cortex	tissue	3.4
Tonsil	tissue	3.4	not detected
Entorhinal cortex	tissue	3.2
Placenta	tissue	2.8	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (248.3), Cerebellar white matter (241.7), Nucleus raphe obscurus (225.0), Nucleus raphe pallidus (212.9), Nucleus ambiguus (211.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREM, DGKQ, ID2, NFKB1, NR1H3, NR5A1, PPARG, RELA, RXRA, SP1, SREBF1, TCF3, USF1

miRNA regulators (miRDB)

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

11 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-3714	99.71	70.74	2671

Functional genomics

gnomAD constraint: pLI 2.34e-17, LOEUF 0.932, missense Z 0.61 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000244289 — one region, missense o/e 0.94.

Literature-anchored findings (GeneRIF, showing 40)

• genes of C3, hormone-sensitive lipase, and PPARgamma may exert a modifying effect on lipid and glucose metabolism in familial combined hypersensitivity (PMID:11979403)
• overexpression of HSL, despite increased lipase activity, does not lead to enhanced lipolysis (PMID:12518034)
• HSL i6 A5 HOMOZYGOSITY IS A RISK FACTOR FOR BODY FAT ACCUMULATION (PMID:12534454)
• high concentrations of estradiol significantly increased both hormone-sensitive lipase expression and glycerol release relative to control (PMID:12701046)
• lipolytic catecholamine resistance of sc adipocytes in polycystic ovary syndrome is probably due to a combination of decreased amounts of beta(2)-adrenergic receptors, the regulatory II beta-component of protein kinase A, and hormone-sensitive lipase (PMID:12727985)
• High adrenaline levels can stimulate hormone-sensitive lipase(HSL) activity regardless of metabolic milieu. Large increases in adrenaline during exercise are able to further stimulate contraction-induced increase in HSL activity. (PMID:12730334)
• The presence of a catalytically inactive variant of this enzyme is associated with decreased lipolysis in abdominal subcutaneous adipose tissue of obese subjects (PMID:12765952)
• role of cyclic GMP in natriuretic peptide-mediated phosphorylation in adipocytes (PMID:12970365)
• AMPK is a major regulator of skeletal muscle HSL activity that can override beta-adrenergic stimulation (PMID:15231718)
• catalytic serine of hormone-sensitive lipase is highly reactive and similar behavior was also observed with lipases with no lid domain covering their active site, or with a deletion in the lid domain (PMID:15260473)
• 5’AMP-activated protein kinase phosphorylates hormone-sensitive lipase on Ser565 in human skeletal muscle during exercise with reduced muscle glycogen. Apparently, HSL Ser565 phosphorylation by AMPK during exercise (PMID:15308678)
• mechanism of infertility in HSL-deficient males is cell autonomous and resides in postmeiotic germ cells, because HSL expression in these cells is in itself sufficient to restore normal fertility (PMID:15345679)
• a pre-lipolysis complex containing at least AFABP and HSL exists (PMID:15456755)
• Basal HSL is decreased in patients with type 2 diabetes mellitus, and this may be a consequence of elevated plasma insulin levels. (PMID:15609025)
• Perilipin targets a novel pool of lipid droplets for lipolytic attack by hormone-sensitive lipase (PMID:16243839)
• the HSL C-60G polymorphism is associated with increased waist circumference in non-obese subjects (PMID:16534522)
• adrenergic stimulation contributes to the increase in HSL activity that occurs in human skeletal muscle in the first minute of exercise at 65% and 90% VO2 peak (PMID:16690773)
• HSL gene expression shows a regulation according to obesity status and is associated with increased adipose tissue lipase activity. (PMID:16752181)
• although HSL expression and Ser(659) phosphorylation in skeletal muscle during exercise is sex specific, total muscle HSL activity measured in vitro was similar between sexes (PMID:16822962)
• maternal type 1 diabetes is associated with TG accumulation and increased EL and HSL gene expression in placenta (PMID:16940551)
• hormone-sensitive lipase (PMID:17026959)
• Adipose triglyceride lipase and hormone sensitive lipase are responsible for more than 95% of the triacylglycerol hydrolase activity present in murine white adipose tissue. (PMID:17074755)
• The combined effect of LIPC, LIPE and ApoCIII gene polymorphisms may increase the likelihood of gestational hypertension, but seemingly not of preeclampsia. (PMID:17318300)
• Adipose triglyceride lipase (ATGL) is less important than hormone-sensitive lipase (HSL) in regulating catecholamine-induced lipolysis. Both lipases regulate basal lipolysis in human adipocytes. ATGL expression is not influenced by obesity or PCOS. (PMID:17327373)
• In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass (PMID:17356053)
• Dydrogesterone and norethisterone increase secretion of HSL from abdominaal adipocytes. (PMID:17587400)
• variation of the HSL gene might be associated with a physiological effect on in vivo beta-adrenoceptor-mediated fat oxidation (PMID:18249203)
• Real-time PCR revealed that large adipocytes expressed higher mRNA levels of hormone sensitive lipase. (PMID:18383440)
• Obesity is accompanied by impaired fasting glycerol release, lower HSL protein expression, and serine phosphorylation. (PMID:18398140)
• Mapping of the hormone-sensitive lipase binding site on the adipocyte fatty acid-binding protein (AFABP). Identification of the charge quartet on the AFABP/aP2 helix-turn-helix domain. (PMID:18820256)
• analysis of human, mouse and ovine Hormone Sensitive Lipase (PMID:18824087)
• PKA activates human HSL against lipid substrates in vitro primarily through phosphorylation of Ser649 and Ser650 (PMID:19018281)
• These results suggest that the associations between physical activity and body fat and plasma lipoprotein/lipid concentrations in men are dependent on the LIPE C-60G polymorphism,. (PMID:19164092)
• results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes (PMID:19433586)
• TNFalpha decreased ATGL and HSL protein content and triglycerides (TG)-hydrolase activity but increased basal lipolysis due to a marked reduction in perilipin (PLIN) protein content (PMID:19695247)
• The present study aimed at comparing expression and subcellular distribution of perilipin and hormone-sensitive lipase in two abdominal adipose tissues of lean and obese women. (PMID:20017959)
• Those findings indicate improvement and conservation of lifestyle depending on genetic predisposition in ADIPOQ, PLIN and LIPE should be encouraged. (PMID:20495294)
• Data show that hormone-sensitive lipase activity is reduced in adipose tissue of patients with and without diabetes, while lipoprotein lipase activity is reduces only in patients with diabetes. (PMID:20926921)
• It is concluded that ACTH via the PKA pathway stimulates expression of SF-1, which activates transcription of LIPE presumably by interaction with putative binding sequences within promoter A (PMID:21081692)
• Studies indicate tha HSL is regulated by reversible phosphorylation on five critical residues. (PMID:21241784)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lipea	ENSDARG00000063037
danio_rerio	lipeb	ENSDARG00000101145
mus_musculus	Lipe	ENSMUSG00000003123
rattus_norvegicus	Lipe	ENSRNOG00000020546
drosophila_melanogaster	Hsl	FBGN0034491
caenorhabditis_elegans		WBGENE00016704

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96790) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 72 distinct phenotype terms.

Mouse phenotype (MP)	Records
male infertility	4
increased circulating glucose level	4
decreased liver triglyceride level	3
increased circulating insulin level	2
oligozoospermia	2
decreased circulating free fatty acids level	2
increased triglyceride level	2
decreased circulating leptin level	2
abnormal white adipose tissue physiology	2
increased pancreatic beta cell mass	2
abnormal seminiferous tubule epithelium morphology	2
decreased circulating adiponectin level	2
increased brown adipose tissue amount	1
abnormal abdominal fat pad morphology	1
increased bone mineral density	1
abnormal circulating cholesterol level	1
abnormal triglyceride level	1
abnormal testis morphology	1
small testis	1
decreased body weight	1
hyperactivity	1
abnormal lipid level	1
increased circulating triglyceride level	1
abnormal circulating free fatty acids level	1
increased circulating free fatty acids level	1

+47 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
Escherichia coli APEC O1	A1A8E2	100.0%	Diamond
Escherichia coli SMS-3-5	B1LJN4	100.0%	Diamond
Escherichia coli str. K-12 substr. DH10B	B1XFR3	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Newport str. SL254	B4SWY4	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Dublin str. CT_02021853	B5FLK0	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Enteritidis str. P125109	B5QU79	100.0%	Diamond
Escherichia coli O157:H7 str. EC4115	B5Z3Y7	100.0%	Diamond
Escherichia coli SE11	B6I0B9	100.0%	Diamond
Escherichia coli 55989	B7L7A1	100.0%	Diamond
Escherichia coli IAI1	B7M3W8	100.0%	Diamond
Escherichia coli S88	B7MDZ8	100.0%	Diamond
Escherichia coli IAI39	B7NIF4	100.0%	Diamond
Escherichia coli BW2952	C4ZUT0	100.0%	Diamond
Escherichia coli K-12	P23872	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WK86	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WK87	100.0%	Diamond
Escherichia coli UTI89	Q1RF59	100.0%	Diamond
Shigella sonnei Ss046	Q3Z4S3	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150	Q5PFJ2	100.0%	Diamond
Escherichia coli O157:H7	Q8XD38	100.0%	Diamond
Escherichia coli HS	A7ZXD4	99.7%	Diamond
Escherichia coli ATCC 8739	B1IZB8	99.7%	Diamond
Shigella boydii CDC 3083-94	B2U4S9	99.7%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi A str. AKU_12601	B5BD42	99.7%	Diamond
Escherichia coli UMN026	B7N929	99.7%	Diamond
Shigella flexneri 5 str. 8401	Q0T7A9	99.7%	Diamond
Shigella boydii Sb227	Q325C0	99.7%	Diamond
Salmonella enterica subsp. enterica serovar Choleraesuis str. SC-B67	Q57S73	99.7%	Diamond
Shigella flexneri	Q83M39	99.7%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	Q8ZRA1	99.7%	Diamond
Tulipa gesneriana	R4X247	99.7%	Diamond
Escherichia coli O139:H28 str. E24377A	A7ZIN6	99.4%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi B str. SPB7	A9MW81	99.4%	Diamond
Salmonella enterica subsp. enterica serovar Schwarzengrund str. CVM19633	B4TMG8	99.4%	Diamond
Salmonella enterica subsp. enterica serovar Agona str. SL483	B5EXN3	99.4%	Diamond
Escherichia coli ED1a	B7MQJ1	99.4%	Diamond
Escherichia coli O127:H6 str. E2348/69	B7UKF6	99.4%	Diamond
Escherichia coli CFT073	Q8FK82	99.4%	Diamond
Salmonella enterica subsp. enterica serovar Typhi	Q8Z8T1	99.4%	Diamond
Pongo abelii	Q5R8Y5	99.0%	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
MIR8077	ncRNA	102465875
CEACAM8	protein-coding	1088
MEGF8	protein-coding	1954
CXCL17	protein-coding	284340
CEACAM1	protein-coding	634
CNFN	protein-coding	84518
LIPE-AS1	ncRNA	100996307
PRR19	protein-coding	284338
TMEM145	protein-coding	284339
PAFAH1B3	protein-coding	5050

Protein

Protein identifiers

Hormone-sensitive lipase — Q05469 (reviewed: Q05469)

Alternative names: Monoacylglycerol lipase LIPE, Retinyl ester hydrolase

All UniProt accessions (7): Q05469, M0QXB1, M0QXM5, M0QY29, M0QYP8, M0R201, M0R2G1

UniProt curated annotations — full annotation on UniProt →

Function. Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters. Shows a preferential hydrolysis of DAGs over TAGs and MAGs and preferentially hydrolyzes the fatty acid (FA) esters at the sn-3 position of the glycerol backbone in DAGs. Preferentially hydrolyzes FA esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs. Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor. In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production.

Subunit / interactions. Monomer and homodimer. Interacts with CAVIN1 in the adipocyte cytoplasm. Interacts with PLIN5.

Subcellular location. Cell membrane. Membrane. Caveola. Cytoplasm. Cytosol. Lipid droplet.

Tissue specificity. Testis.

Post-translational modifications. Phosphorylation by AMPK reduces its translocation towards the lipid droplets.

Disease relevance. Lipodystrophy, familial partial, 6 (FPLD6) [MIM:615980] An autosomal recessive form of lipodystrophy characterized by abnormal subcutaneous fat distribution. Affected individuals have increased visceral fat, impaired lipolysis, dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes. Some patients manifest muscular dystrophy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Retinyl ester hydrolase is inhibited by bis-p-nitrophenyl phosphate.

Pathway. Glycerolipid metabolism; triacylglycerol degradation.

Similarity. Belongs to the ‘GDXG’ lipolytic enzyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q05469-1	1, Testicular	yes
Q05469-2	2

RefSeq proteins (10): NP_001403029, NP_001403030, NP_001403031, NP_001403032, NP_001403033, NP_001403034, NP_001403035, NP_001403036, NP_001403037, NP_005348* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002168	Aes_GDXG_HIS_AS	Active_site
IPR010468	HSL_N	Domain
IPR013094	AB_hydrolase_3	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR033140	Lipase_GDXG_put_SER_AS	Active_site

Pfam: PF06350, PF07859

Enzyme classification (BRENDA)

• EC 3.1.1.79 — hormone-sensitive lipase (BRENDA: 22 organisms, 222 substrates, 108 inhibitors, 149 Km, 116 kcat entries)

Substrate kinetics (BRENDA)

64 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FLUORESCEIN DIACETOXYMETHYL ETHER	0.0002–0.082	18
FLUORESCEIN DI(METHOXY)ACETOXYMETHYL ETHER	0.0011–0.694	17
FLUORESCEIN BIS((5-OXAZOLYL)CARBOXYMETHYL ETHER)	—	15
CHOLESTERYL OLEATE	0.0022–0.099	9
4-NITROPHENYL ACETATE	0.28–7.42	7
4-NITROPHENYL BUTYRATE	0.02–1.97	5
4-NITROPHENYL OLEATE	0.268–0.462	4
P-NITROPHENYL ACETATE	0.28–7.42	4
2-NAPHTHYL ACETATE	0.0077–5.43	2
4-NITROPHENYL HEXANOATE	1.4–2.32	2
4-NITROPHENYL PALMITATE	0.363–0.376	2
P-NITROPHENYL BUTYRATE	0.164–1.06	2
P-NITROPHENYL HEXANOATE	0.03–0.054	2
VINYL ACETATE	170–315	2
VINYL BUTYRATE	10–25	2

Catalyzed reactions (Rhea)

• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)
• all-trans-retinyl hexadecanoate + H2O = all-trans-retinol + hexadecanoate + H(+) (RHEA:13933)
• a monoacylglycerol + H2O = glycerol + a fatty acid + H(+) (RHEA:15245)
• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:26132)
• a diacylglycerol + H2O = a monoacylglycerol + a fatty acid + H(+) (RHEA:32731)
• cholesteryl (9Z-octadecenoate) + H2O = cholesterol + (9Z)-octadecenoate + H(+) (RHEA:33875)
• 1,2-di-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H(+) = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O (RHEA:38379)
• 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = 2-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38383)
• 1,2-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38455)
• 1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38487)
• 2-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38491)
• 1-O-hexadecyl-2-acetyl-sn-glycerol + H2O = 1-O-hexadecyl-sn-glycerol + acetate + H(+) (RHEA:38563)

UniProt features (91 total): helix 26, strand 15, turn 11, compositionally biased region 10, sequence variant 10, modified residue 6, region of interest 4, active site 3, sequence conflict 3, chain 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structure by resolution:

PDB	Title	Method	Resolution (Å)
8ZVQ	Cryo-EM Structure of Human Hormone-sensitive Lipase (HSL)	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05469-F1	64.77	0.37

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Other congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH enhanced · IF supported

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
725
994
1024

Post-translational modifications (6)

Type	Positions
Phosphoserine	853, 855, 897, 929, 950, 951

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 10; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

10 pathways:

ID	Pathway	Evidence
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-556833	Metabolism of lipids	—
R-HSA-163560	Triglyceride catabolism	electronic
R-HSA-8979227	Triglyceride metabolism	—

MSigDB gene sets: 249 (showing top): REACTOME_TRIGLYCERIDE_CATABOLISM, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, GOBP_LIPID_METABOLIC_PROCESS, GOBP_TRIGLYCERIDE_CATABOLIC_PROCESS, MAGRANGEAS_MULTIPLE_MYELOMA_IGG_VS_IGA_UP, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_DN, GOBP_DIACYLGLYCEROL_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_CATABOLIC_PROCESS

GO Biological Process (9): protein phosphorylation (GO:0006468), cholesterol metabolic process (GO:0008203), lipid catabolic process (GO:0016042), triglyceride catabolic process (GO:0019433), diacylglycerol catabolic process (GO:0046340), ether lipid metabolic process (GO:0046485), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202), retinol metabolic process (GO:0042572)

GO Molecular Function (9): sterol ester esterase activity (GO:0004771), triacylglycerol lipase activity (GO:0004806), monoacylglycerol lipase activity (GO:0047372), all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity (GO:0047376), retinyl-palmitate esterase activity (GO:0050253), diacylglycerol lipase activity (GO:0120516), protein binding (GO:0005515), lipase activity (GO:0016298), hydrolase activity (GO:0016787)

GO Cellular Component (5): lipid droplet (GO:0005811), cytosol (GO:0005829), caveola (GO:0005901), membrane (GO:0016020), plasma membrane (GO:0005886)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Triglyceride metabolism	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Gene expression (Transcription)	1
Metabolism	1
Metabolism of lipids	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1
Epigenetic regulation of gene expression	1

GO top-level categories

27 GO namespaces:

Category	Terms
lipase activity	4
carboxylic ester hydrolase activity	4
lipid metabolic process	3
acylglycerol catabolic process	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
catabolic process	1
triglyceride metabolic process	1
diacylglycerol metabolic process	1
primary metabolic process	1
retinoid metabolic process	1
primary alcohol metabolic process	1
hormone metabolic process	1
olefinic compound metabolic process	1
retinyl-palmitate esterase activity	1
retinol metabolic process	1
binding	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1
intracellular membraneless organelle	1
cytoplasm	1
plasma membrane raft	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
diacylglycerol lipase activity	MF	direct assay
retinyl-palmitate esterase activity	MF	direct assay
sterol ester esterase activity	MF	direct assay
triacylglycerol lipase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,022 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPE	PNPLA2	Q96AD5	966
LIPE	PLIN1	O60240	938
LIPE	MGLL	Q99685	919
LIPE	ABHD5	Q8WTS1	899
LIPE	LPL	P06858	882
LIPE	PNPLA3	Q9NST1	848
LIPE	PPARG	P37231	834
LIPE	INS	P01308	832
LIPE	PPARA	Q07869	800
LIPE	UCP1	P25874	786
LIPE	SLC2A4	P14672	785
LIPE	PRKACA	P17612	784
LIPE	PRKACG	P22612	782
LIPE	PRKACB	P22694	782
LIPE	ACSF2	Q96CM8	782

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
TSGA10IP	physical association	0.560	3
MTNR1A	physical association	0.000	1
NSFL1C	physical association	0.000	1

BioGRID (24 interactions; top human partners by supporting records): PLIN1 (FRET; 4 records), PTRF (Co-fractionation; 3 records), FABP4 (FRET; 2 records), PLIN2 (FRET; 2 records), PLIN5 (FRET; 2 records), ARF6 (Proximity Label-MS), GPR182 (Affinity Capture-MS), MTNR1A (Two-hybrid), NSFL1C (Two-hybrid), PARP9 (Proximity Label-MS), PLIN3 (Affinity Capture-Western), PRNP (Affinity Capture-MS), RELA (Affinity Capture-MS), TOPBP1 (Proximity Label-MS), TSGA10IP (Two-hybrid)

SIGNOR signaling

showing 10 of 13 signaling interactions:

A	Effect	B	Mechanism
AMPK	down-regulates	LIPE	phosphorylation
CAMK2A	down-regulates	LIPE	phosphorylation
PRKAA1	down-regulates	LIPE	phosphorylation
PRKACA	down-regulates	LIPE	phosphorylation
PRKACA	“up-regulates activity”	LIPE	phosphorylation
MAPK1	“up-regulates activity”	LIPE	phosphorylation
MAPK3	“up-regulates activity”	LIPE	phosphorylation
Gbeta	“up-regulates activity”	LIPE	phosphorylation
ERK1/2	“up-regulates activity”	LIPE	phosphorylation
PKA	“up-regulates activity”	LIPE	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for LIPE: 300 ClinVar records (8 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	5
Uncertain significance	187
Likely benign	54
Benign	35

Top pathogenic / likely-pathogenic (8)

Showing all 8 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
1028370	NM_005357.4(LIPE):c.2152C>T (p.Arg718Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
4682129	NM_005357.4(LIPE):c.1111_1120dup (p.Arg374fs)	Pathogenic	criteria provided, single submitter	1
4682134	NM_005357.4(LIPE):c.235del (p.Gln79fs)	Pathogenic	criteria provided, single submitter	1
522594	NM_005357.4(LIPE):c.3103G>T (p.Glu1035Ter)	Likely pathogenic	criteria provided, single submitter	2
4845693	NM_005357.4(LIPE):c.232C>T (p.Gln78Ter)	Likely pathogenic	criteria provided, single submitter	1
4942738	NM_005357.4(LIPE):c.2212dup (p.Ala738fs)	Likely pathogenic	criteria provided, single submitter	1
4942739	NM_005357.4(LIPE):c.2062G>T (p.Glu688Ter)	Likely pathogenic	criteria provided, single submitter	1
180647	NM_005357.4(LIPE):c.1519_1520dup (p.Ser508fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore LIPE’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; 40 predictions of 983):

Position(s)	Effect	Δscore	Sites
19:42402076–42402077	acceptor_loss	1.0000	5
19:42405384	donor_loss	1.0000
19:42405562–42405563	acceptor_loss	1.0000	5
19:42407172–42407173	donor_loss	1.0000	4
19:42407469–42407470	acceptor_loss	1.0000	6
19:42407604–42407605	donor_loss	1.0000	5
19:42407792–42407793	acceptor_loss	1.0000	6
19:42407974–42407975	donor_loss	1.0000	6
19:42407987	donor_gain	1.0000
19:42408014	donor_gain	1.0000

AlphaMissense

1,734 missense substitutions predicted likely pathogenic (of 6,875 scored), across 465 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
D724	8	0.989	0.998
H663	8	0.988	0.996
H651	8	0.987	0.998
D998	8	0.983	0.995
D994	8	0.982	0.992
H1024	8	0.980	0.996
S725	8	0.977	0.998
D772	8	0.975	0.988
F655	8	0.970	0.999
F1026	8	0.970	0.999
H649	8	0.968	0.996
D999	8	0.964	0.992
F472	8	0.962	0.996
F403	8	0.958	0.992
F538	8	0.942	0.991
D682	8	0.942	0.987
D363	8	0.937	0.970
F691	8	0.937	0.995
F465	8	0.935	0.987
F402	8	0.895	0.968

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	4.01e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	9.48e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000104
Pancreatic Adenocarcinoma (TCGA)	favorable	0.000379

Disease associations

OMIM: gene MIM:151750 | disease phenotypes: MIM:615980 (Lipodystrophy, familial partial, type 6)

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
LIPE-related familial partial lipodystrophy	Strong	Autosomal recessive	3

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
LIPE-related familial partial lipodystrophy	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Insulin resistance (including lipodystrophy)	green
Severe insulin resistance and lipodystrophy syndromes	green

Mondo (1): LIPE-related familial partial lipodystrophy (MONDO:0014431)

Orphanet (1): LIPE-related familial partial lipodystrophy (Orphanet:435660)

HPO phenotypes

37 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0000468	Increased adipose tissue around the neck
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000855	Insulin resistance
HP:0000876	Oligomenorrhea
HP:0000956	Acanthosis nigricans
HP:0001010	Hypopigmentation of the skin
HP:0001324	Muscle weakness
HP:0001397	Hepatic steatosis
HP:0001761	Pes cavus
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002938	Lumbar hyperlordosis
HP:0003077	Hyperlipidemia
HP:0003119	Abnormal circulating lipid concentration
HP:0003198	Myopathy
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase activity
HP:0003292	Decreased serum leptin
HP:0003551	Difficulty climbing stairs
HP:0003560	Muscular dystrophy
HP:0003635	Loss of subcutaneous adipose tissue in limbs
HP:0003701	Proximal muscle weakness
HP:0003712	Skeletal muscle hypertrophy
HP:0007340	Lower limb muscle weakness
HP:0008993	Increased intraabdominal fat
HP:0008994	Proximal lower limb muscle weakness
HP:0008997	Proximal upper limb muscle weakness
HP:0009017	Loss of gluteal subcutaneous adipose tissue
HP:0009125	Lipodystrophy
HP:0011462	Young adult onset
HP:0012743	Abdominal obesity
HP:0012881	Abnormal labia majora morphology
HP:0030685	Decreased adiponectin level

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3590 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 41 [PMID: 15026062]	Inhibition	9.0	pIC50

Binding affinities (BindingDB)

259 measured of 342 human assays (342 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(4-(3-fluorophenyl)piperidine-1-carbonyl)-4-(2-methoxyethyl)-3-methylisoxazol-5(2H)-one	IC50	0.2 nM
Morpholin-4-yl-carbamic acid 4-[(4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester	IC50	1 nM
4-Isopropyl-2-[4-(3-methoxy-phenyl)-piperazine-1-carbonyl]-3-methyl-2H-isoxazol-5-one	IC50	1 nM
4-butyl-3-methyl-2-(4-methylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	1 nM
4-Isopropyl-3-methyl-2-(piperidine-1-carbonyl)-2H-isoxazol-5-one	IC50	2 nM
4-Isopropyl-3-methyl-5-oxo-5H-isoxazole-2-carboxylic acid methyl-thiophen-2-ylmethyl-amide	IC50	2 nM
3-methyl-4-(2-phenoxyethyl)-2-(piperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	2 nM
CHEMBL4063082	IC50	2 nM
(5S,7S,8R)-8-hydroxy-7-propan-2-yl-2-[4-(2,2,2-trifluoroethoxy)phenyl]-2-azaspiro[4.5]decan-1-one	IC50	2.4 nM	US-8722721: SEC-hydroxycyclohexyl derivatives
(3,4-Dihydro-1H-isoquinolin-2-yl)-carbamic acid 4-tert-butoxycarbonylamino-phenyl ester	IC50	3 nM
(5S,7R,8R)-8-hydroxy-7-propyl-2-[4-(2,2,2-trifluoroethoxy)phenyl]-2-azaspiro[4.5]decan-1-one	IC50	3.7 nM	US-8722721: SEC-hydroxycyclohexyl derivatives
4-Isopropyl-3-methyl-5-oxo-5H-isoxazole-2-carboxylic acid furan-2-ylmethyl-methyl-amide	IC50	4 nM
[4-(Morpholin-4-ylcarbamoyloxy)-phenyl]-acetic acid benzyl ester	IC50	5 nM
N-benzyl-4-isopropyl-N,3-dimethyl-5-oxoisoxazole-2(5H)-carboxamide	IC50	5 nM
4-Benzyl-3-methyl-2-(piperidine-1-carbonyl)-2H-isoxazol-5-one	IC50	5 nM
CHEMBL3814077	IC50	7 nM
8-hydroxy-8-[(2-oxopyrrolidin-1-yl)methyl]-2-[4-(trifluoromethyl)phenyl]-2-azaspiro[4.5]decan-1-one	IC50	7.7 nM	US-8703807: Azaspirodecanone compounds
CHEMBL4101186	IC50	8 nM
CHEMBL4063918	IC50	8 nM
N-cyclohexyl-4-isopropyl-N,3-dimethyl-5-oxoisoxazole-2(5H)-carboxamide	IC50	9 nM
8-(2-fluoroethoxymethyl)-8-hydroxy-2-[6-[(2S)-1,1,1-trifluoropropan-2-yl]oxy-3-pyridinyl]-2-azaspiro[4.5]decan-1-one	IC50	10 nM	US-8703807: Azaspirodecanone compounds
Morpholin-4-yl-carbamic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester	IC50	10 nM
4-isobutyl-3-methyl-2-(4-phenylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	10 nM
N-(2-fluorobenzyl)-4-isopropyl-N,3-dimethyl-5-oxoisoxazole-2(5H)-carboxamide	IC50	10 nM
4-(2-methoxyethyl)-3-methyl-2-(piperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	10 nM
3-Methyl-2-(piperidine-1-carbonyl)-4-(tetrahydro-thiopyran-4-yl)-2H-isoxazol-5-one	IC50	11 nM
4-(2-methoxyethyl)-3-methyl-2-(4-phenylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	11 nM
4-cyclohexyl-3-methyl-2-(piperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	11 nM
2-[4-(3-Fluoro-phenyl)-piperidine-1-carbonyl]-4-isopropyl-3-methyl-2H-isoxazol-5-one	IC50	12 nM
4-Isopropyl-3-methyl-5-oxo-5H-isoxazole-2-carboxylic acid (3-fluoro-benzyl)-methyl-amide	IC50	12 nM
4-isopropyl-3-methyl-2-(4-phenylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	12 nM
3,4-dimethyl-2-(piperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	13 nM
CHEMBL4084740	IC50	13 nM
8-hydroxy-2-(6-propan-2-yloxy-3-pyridinyl)-8-(2,2,2-trifluoroethoxymethyl)-2-azaspiro[4.5]decan-1-one	IC50	13.7 nM	US-8703807: Azaspirodecanone compounds
3-Methyl-4-phenyl-2-(piperidine-1-carbonyl)-2H-isoxazol-5-one	IC50	14 nM
4-tert-butyl-3-methyl-2-(piperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	14 nM
CHEMBL4093111	IC50	14 nM
4-isopropyl-3-methyl-2-(pyrrolidine-1-carbonyl)isoxazol-5(2H)-one	IC50	15 nM
CHEMBL4100232	IC50	16 nM
(5S,7S,8R)-8-hydroxy-7-propan-2-yl-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one	IC50	16.2 nM	US-8722721: SEC-hydroxycyclohexyl derivatives
8-(2,2-difluoroethoxymethyl)-8-hydroxy-2-(4-propan-2-yloxyphenyl)-2-azaspiro[4.5]decan-1-one	IC50	16.3 nM	US-8703807: Azaspirodecanone compounds
4-{[(1H-Indol-2-yl)-methyl-amino]-methyl}-3-methyl-2-(piperidine-1-carbonyl)-2H-isoxazol-5-one	IC50	17 nM
4-Isopropyl-3-methyl-5-oxo-5H-isoxazole-2-carboxylic acid (4-chloro-phenyl)-methyl-amide	IC50	17 nM
4-isobutyl-3-methyl-2-(4-methylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	18 nM
4-ethyl-3-methyl-2-(piperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	18 nM
(3,4-Dihydro-1H-isoquinolin-2-yl)-carbamic acid 4-chloro-phenyl ester	IC50	19 nM
CHEMBL4085494	IC50	19 nM
4-(2-ethoxyethyl)-3-methyl-2-(4-methylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	20 nM
4-cyclohexyl-3-methyl-2-(4-methylpiperidine-1-carbonyl)isoxazol-5(2H)-one	IC50	20 nM
CHEMBL4074445	IC50	20 nM

ChEMBL bioactivities

388 potent at pChembl≥5 of 390 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL106375
9.00	IC50	1	nM	CHEMBL419197
9.00	IC50	1	nM	CHEMBL322794
9.00	IC50	1	nM	CHEMBL49895
8.70	IC50	2	nM	CHEMBL107197
8.70	IC50	2	nM	CHEMBL110343
8.70	IC50	2	nM	CHEMBL109116
8.70	IC50	2	nM	CHEMBL4063082
8.62	IC50	2.4	nM	CHEMBL3643710
8.52	IC50	3	nM	CHEMBL107197
8.52	IC50	3	nM	CHEMBL320813
8.52	IC50	3	nM	CHEMBL295166
8.52	IC50	3	nM	CHEMBL106581
8.52	IC50	3	nM	CHEMBL106126
8.43	IC50	3.7	nM	CHEMBL3643709
8.40	IC50	4	nM	CHEMBL105834
8.40	IC50	4	nM	CHEMBL110763
8.40	IC50	4	nM	CHEMBL110343
8.40	IC50	4	nM	CHEMBL317407
8.40	IC50	4	nM	CHEMBL108523
8.40	IC50	4	nM	CHEMBL106784
8.40	IC50	4	nM	CHEMBL106756
8.30	IC50	5	nM	CHEMBL107365
8.30	IC50	5	nM	CHEMBL49417
8.30	IC50	5	nM	CHEMBL106045
8.30	IC50	5	nM	CHEMBL110653
8.30	IC50	5	nM	CHEMBL320249
8.30	IC50	5	nM	CHEMBL106314
8.22	IC50	6	nM	CHEMBL110716
8.22	IC50	6	nM	CHEMBL321903
8.22	IC50	6	nM	CHEMBL316549
8.22	IC50	6	nM	CHEMBL108325
8.22	IC50	6	nM	CHEMBL110655
8.22	IC50	6	nM	CHEMBL108519
8.22	IC50	6	nM	CHEMBL106200
8.15	IC50	7	nM	CHEMBL108207
8.15	IC50	7	nM	CHEMBL3814077
8.15	IC50	7	nM	CHEMBL110597
8.15	IC50	7	nM	CHEMBL321483
8.11	IC50	7.7	nM	CHEMBL3690093
8.10	IC50	8	nM	CHEMBL324436
8.10	IC50	8	nM	CHEMBL4101186
8.10	IC50	8	nM	CHEMBL4063918
8.10	IC50	8	nM	CHEMBL320708
8.05	IC50	9	nM	CHEMBL322051
8.05	IC50	9	nM	CHEMBL106756
8.00	IC50	10	nM	CHEMBL105834
8.00	IC50	10	nM	CHEMBL322794
8.00	IC50	10	nM	CHEMBL49896
8.00	IC50	10	nM	CHEMBL3644849

PubChem BioAssay actives

268 with measured affinity, of 387 total; 50 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
2-[4-(3-fluorophenyl)piperidine-1-carbonyl]-4-(2-methoxyethyl)-3-methyl-1,2-oxazol-5-one	3416: Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	ic50	0.0002	uM
[4-[(4-tert-butylcyclohexanecarbonyl)amino]phenyl] N-morpholin-4-ylcarbamate	90857: Inhibition of human recombinant hormone sensitive lipase.	ic50	0.0010	uM
4-butyl-3-methyl-2-(4-methylpiperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0010	uM
2-[4-(3-methoxyphenyl)piperazine-1-carbonyl]-3-methyl-4-propan-2-yl-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0010	uM
[5-chloro-2-[[6-[4-(trifluoromethyl)phenoxy]pyridine-3-carbonyl]amino]phenyl]boronic acid	1432867: Inhibition of recombinant human HSL expressed in baculovirus infected sf9 cells using PNPB as substrate after 5 mins by spectrophotometric method	ic50	0.0020	uM
3-methyl-2-(piperidine-1-carbonyl)-4-propan-2-yl-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0020	uM
3-methyl-4-(2-phenoxyethyl)-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	3416: Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	ic50	0.0020	uM
N,3-dimethyl-5-oxo-4-propan-2-yl-N-(thiophen-2-ylmethyl)-1,2-oxazole-2-carboxamide	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0020	uM
3-methyl-2-[(3S)-3-methylpiperidine-1-carbonyl]-4-propan-2-yl-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0030	uM
[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl] N-(3,4-dihydro-1H-isoquinolin-2-yl)carbamate	90857: Inhibition of human recombinant hormone sensitive lipase.	ic50	0.0030	uM
4-(2-ethoxyethyl)-3-methyl-2-(4-methylpiperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0030	uM
3-methyl-2-(4-methylpiperidine-1-carbonyl)-4-(2-methylpropyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0030	uM
4-cyclohexyl-3-methyl-2-(4-methylpiperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0040	uM
N-[(2-fluorophenyl)methyl]-N,3-dimethyl-5-oxo-4-propan-2-yl-1,2-oxazole-2-carboxamide	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0040	uM
3-methyl-4-(2-methylpropyl)-2-(4-phenylpiperidine-1-carbonyl)-1,2-oxazol-5-one	3416: Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	ic50	0.0040	uM
4-(2-methoxyethyl)-3-methyl-2-[4-(3-methylphenyl)piperidine-1-carbonyl]-1,2-oxazol-5-one	3416: Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	ic50	0.0040	uM
2-[4-(3-fluorophenyl)piperidine-1-carbonyl]-3-methyl-4-propan-2-yl-1,2-oxazol-5-one	3416: Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	ic50	0.0040	uM
N-(furan-2-ylmethyl)-N,3-dimethyl-5-oxo-4-propan-2-yl-1,2-oxazole-2-carboxamide	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0040	uM
benzyl 2-[4-(morpholin-4-ylcarbamoyloxy)phenyl]acetate	90857: Inhibition of human recombinant hormone sensitive lipase.	ic50	0.0050	uM
3-methyl-4-(2-methylpropyl)-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0050	uM
4-benzyl-3-methyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0050	uM
N-[(3-fluorophenyl)methyl]-N,3-dimethyl-5-oxo-4-propan-2-yl-1,2-oxazole-2-carboxamide	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0050	uM
4-(2-methoxyethyl)-3-methyl-2-(4-phenylpiperidine-1-carbonyl)-1,2-oxazol-5-one	3416: Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	ic50	0.0050	uM
N-benzyl-N,3-dimethyl-5-oxo-4-propan-2-yl-1,2-oxazole-2-carboxamide	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0050	uM
4-(4-chlorophenyl)sulfanyl-3-methyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0060	uM
3-methyl-2-(4-methylpiperidine-1-carbonyl)-4-(thian-4-yl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0060	uM
3-methyl-4-phenylsulfanyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0060	uM
3-methyl-2-(4-methylpiperidine-1-carbonyl)-4-propan-2-yl-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0060	uM
4-cyclopentyl-3-methyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0060	uM
ethyl 1-(3-methyl-5-oxo-4-propan-2-yl-1,2-oxazole-2-carbonyl)piperidine-4-carboxylate	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0060	uM
3-methyl-2-(4-phenylpiperazine-1-carbonyl)-4-propan-2-yl-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0060	uM
[2-[[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methoxy]phenyl]boronic acid	1306885: Inhibition of recombinant human HSL expressed in Sf9 insect cells using PNPB as substrate measured after 5 mins by spectrophotometric method	ic50	0.0070	uM
4-butyl-3-methyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0070	uM
N,3-dimethyl-5-oxo-N-phenyl-4-propan-2-yl-1,2-oxazole-2-carboxamide	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0070	uM
2-(3,3-dimethylpiperidine-1-carbonyl)-3-methyl-4-propan-2-yl-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0070	uM
[5-chloro-2-[2-oxo-2-[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]piperidin-1-yl]ethyl]phenyl]boronic acid	1461939: Inhibition of recombinant human HSL expressed in baculovirus infected sf9 insect cells using PNPB as substrate after 5 mins by spectrophotometric analysis	ic50	0.0080	uM
N-[4-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-6-[4-(trifluoromethyl)phenoxy]pyridine-3-carboxamide	1432867: Inhibition of recombinant human HSL expressed in baculovirus infected sf9 cells using PNPB as substrate after 5 mins by spectrophotometric method	ic50	0.0080	uM
4-cyclopentyl-3-methyl-2-(4-phenylpiperidine-1-carbonyl)-1,2-oxazol-5-one	3416: Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	ic50	0.0080	uM
3-methyl-4-propan-2-yl-2-(thiomorpholine-4-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0080	uM
N-cyclohexyl-N,3-dimethyl-5-oxo-4-propan-2-yl-1,2-oxazole-2-carboxamide	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0090	uM
[4-(cyclohexanecarbonylamino)phenyl] N-morpholin-4-ylcarbamate	90857: Inhibition of human recombinant hormone sensitive lipase.	ic50	0.0100	uM
4-(2-methoxyethyl)-3-methyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0100	uM
3-methyl-2-(piperidine-1-carbonyl)-4-(thian-4-yl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0110	uM
4-cyclohexyl-3-methyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0110	uM
3-methyl-2-(4-phenylpiperidine-1-carbonyl)-4-propan-2-yl-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0120	uM
[5-fluoro-2-[[6-[4-(trifluoromethyl)phenoxy]pyridine-3-carbonyl]amino]phenyl]boronic acid	1432867: Inhibition of recombinant human HSL expressed in baculovirus infected sf9 cells using PNPB as substrate after 5 mins by spectrophotometric method	ic50	0.0130	uM
3,4-dimethyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0130	uM
N-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-6-[4-(trifluoromethyl)phenoxy]pyridine-3-carboxamide	1432867: Inhibition of recombinant human HSL expressed in baculovirus infected sf9 cells using PNPB as substrate after 5 mins by spectrophotometric method	ic50	0.0140	uM
4-tert-butyl-3-methyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0140	uM
3-methyl-4-phenyl-2-(piperidine-1-carbonyl)-1,2-oxazol-5-one	90855: Inhibition of human recombinant hormone sensitive lipase (HSL)	ic50	0.0140	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol S	increases expression	3
nuciferine	decreases expression, decreases reaction	2
cobaltous chloride	decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Dietary Carbohydrates	decreases expression, affects cotreatment, affects expression	2
Niacin	decreases activity, decreases expression	2
Palmitic Acid	decreases expression, decreases reaction	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
retinol palmitate	decreases reaction, increases hydrolysis	1
mono-(2-ethylhexyl)phthalate	increases expression	1
2-chloroethyl ethyl sulfide	increases phosphorylation	1
tuberostemonine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
bisphenol B	increases expression	1
chiglitazar	increases expression	1
dorsomorphin	decreases expression, decreases reaction	1
jinfukang	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Tenofovir	affects expression	1
Rosiglitazone	increases expression	1
Sunitinib	decreases expression	1
Cyclic AMP	increases activity	1
Adenosine Triphosphate	increases activity	1
Cisplatin	affects cotreatment, increases expression	1
Deferoxamine	decreases expression	1
Dexamethasone	increases expression	1

ChEMBL screening assays

27 unique, capped per target: 25 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3606467	Binding	Inhibition of HSL (unknown origin)	Carbamoyl Triazoles, Known Serine Protease Inhibitors, Are a Potent New Class of Antimalarials. — *J Med Chem*
CHEMBL615539	Functional	Inhibition of forskolin-stimulated lipolysis in differentiated 3T3-L1 cells	In vitro SAR of (5-(2H)-isoxazolonyl) ureas, potent inhibitors of hormone-sensitive lipase. — *Bioorg Med Chem Lett*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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