Details for: LIPE

Gene ID: 3991

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: LIPE

Ensembl ID: ENSG00000079435

Description: lipase E, hormone sensitive type

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • adipocyte CL0000136
    CSI 18.59
    rCSI 23.87%
    PRS 93.08
  • epicardial adipocyte CL1000309
    CSI 9.22
    rCSI 30%
    PRS 95.63
  • epithelial cell CL0000066
    CSI 4.97
    rCSI 7.63%
    PRS 89.6
  • subcutaneous adipocyte CL0002521
    CSI 4.33
    rCSI 22.16%
    PRS 98.16
  • cerebellar granule cell CL0001031
    CSI 3.65
    rCSI 5.37%
    PRS 94.38
  • cerebral cortex endothelial cell CL1001602
    CSI 3.55
    rCSI 6.13%
    PRS 95.14
  • inhibitory interneuron CL0000498
    CSI 3.26
    rCSI 7.53%
    PRS 92.71
  • ependymal cell CL0000065
    CSI 3.19
    rCSI 6.47%
    PRS 87.21
  • retinal bipolar neuron CL0000748
    CSI 3.06
    rCSI 5.73%
    PRS 93.09
  • endothelial cell of vascular tree CL0002139
    CSI 2.45
    rCSI 13.41%
    PRS 94.82
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.42
    rCSI 2.89%
    PRS 91.74
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.4
    rCSI 2.98%
    PRS 90.29
  • mesothelial cell CL0000077
    CSI 2.38
    rCSI 9.31%
    PRS 89.59
  • retinal cone cell CL0000573
    CSI 2.29
    rCSI 3.69%
    PRS 92.84
  • retinal pigment epithelial cell CL0002586
    CSI 2.1
    rCSI 4.17%
    PRS 95.32
  • neural cell CL0002319
    CSI 1.95
    rCSI 7.37%
    PRS 89.2
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.69
    rCSI 2.71%
    PRS 92.1
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.4
    rCSI 2.35%
    PRS 91.88
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.9
    rCSI 2.19%
    PRS 90.29
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.68
    rCSI 2.44%
    PRS 90.48

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [LIPE](/details-gene/3991) encodes hormone-sensitive lipase (HSL), a crucial intracellular enzyme responsible for mobilizing stored fats. It primarily catalyzes the hydrolysis of triacylglycerols, diacylglycerols, and cholesteryl esters, releasing fatty acids and glycerol for use as energy substrates by other tissues. Expression data strongly indicates that [LIPE](/details-gene/3991) is a defining functional protein in [adipocytes](/details-cell/CL0000136), the body's primary fat-storing cells. Its activity is tightly regulated by hormones such as catecholamines and insulin, placing it at a central control point in whole-body energy homeostasis. Genetic variations in [LIPE](/details-gene/3991) have been associated with metabolic disorders, including an increased risk for type 2 diabetes ([Link](https://doi.org/10.1056/nejmoa1315496)), highlighting its clinical significance ([151750](https://omim.org/entry/151750)). ## Cellular Roles and Expression Landscape The expression profile of [LIPE](/details-gene/3991) firmly establishes its role as a key enzyme in lipid metabolism, with a striking specificity for adipose tissue. **Overall**, the gene shows the highest significance in [adipocyte](/details-cell/CL0000136) (CSI: 18.59), including specialized subtypes like the [epicardial adipocyte](/details-cell/CL1000309) (CSI: 9.22) and [subcutaneous adipocyte](/details-cell/CL0002521) (CSI: 4.33). This high significance underscores its central function in the mobilization of stored lipids from these cells. Its localization to [lipid droplets](/details-cell/GO:0005811) and the [cytosol](/details-cell/GO:0005829) is consistent with its role in accessing and breaking down fat stores within these cells. Beyond adipose tissue, [LIPE](/details-gene/3991) displays notable, albeit lower, significance in a diverse set of other cell types. These include [epithelial cells](/details-cell/CL0000066), various neuronal populations such as [cerebellar granule cells](/details-cell/CL0001031) and [inhibitory interneurons](/details-cell/CL0000498), as well as [endothelial cells](/details-cell/CL0002139). This broader expression pattern suggests that local lipid mobilization mediated by [LIPE](/details-gene/3991) may also be important for the metabolic or signaling functions of non-adipose tissues, such as providing energy substrates in the brain or participating in retinol metabolism in epithelial contexts ([Link](https://doi.org/10.1111/j.0022-202x.2005.23761.x)). ## Pathways and Molecular Function The molecular functions and pathway involvements of [LIPE](/details-gene/3991) are centered on the catabolism of lipids and sterols, consistent with its enzymatic identity. Functionally, [LIPE](/details-gene/3991) is annotated with multiple lipase activities, including 'Triacylglycerol lipase activity' ([GO:0004806](https://www.ebi.ac.uk/QuickGO/term/GO:0004806)), 'Diacylglycerol lipase activity' ([GO:0120516](https://www.ebi.ac.uk/QuickGO/term/GO:0120516)), and 'Sterol ester esterase activity' ([GO:0004771](https://www.ebi.ac.uk/QuickGO/term/GO:0004771)). These functions directly support its role in biological processes such as 'Triglyceride catabolic process' ([GO:0019433](https://www.ebi.ac.uk/QuickGO/term/GO:0019433)) and 'Cholesterol metabolic process' ([GO:0008203](https://www.ebi.ac.uk/QuickGO/term/GO:0008203)). Its involvement in the Reactome pathway 'Triglyceride catabolism' ([R-HSA-163560](https://reactome.org/content/detail/R-HSA-163560)) and the broader 'Metabolism of lipids' ([R-HSA-556833](https://reactome.org/content/detail/R-HSA-556833)) pathway further solidifies its primary role in energy mobilization from fat stores. Interestingly, [LIPE](/details-gene/3991) is also involved in the 'Retinol metabolic process' ([GO:0042572](https://www.ebi.ac.uk/QuickGO/term/GO:0042572)), which may be particularly relevant in tissues like the retina or skin. Furthermore, its annotation in pathways related to 'Epigenetic regulation of gene expression' ([R-HSA-212165](https://reactome.org/content/detail/R-HSA-212165)) suggests a potential, less-defined role in transcriptional control, possibly through the generation of lipid-derived signaling molecules that influence gene expression programs like adipogenesis. ## Research Directions The central role of [LIPE](/details-gene/3991) in lipid metabolism and its association with metabolic diseases make it a subject of significant research interest. Understanding its tissue-specific functions and regulation is key to elucidating its contribution to health and disease. ### Proposed Hypotheses: 1. **Hypothesis 1:** The high significance of [LIPE](/details-gene/3991) in [epicardial adipocytes](/details-cell/CL1000309) suggests that its dysregulation in this specific fat depot contributes to cardiovascular pathology. Altered [LIPE](/details-gene/3991) activity could lead to aberrant local release of free fatty acids, promoting inflammation and insulin resistance in the adjacent myocardium and coronary arteries. 2. **Hypothesis 2:** The expression of [LIPE](/details-gene/3991) in neuronal cell types, such as [cerebellar granule cells](/details-cell/CL0001031), is essential for maintaining local energy homeostasis and neuronal function. A decline in neuronal [LIPE](/details-gene/3991)-mediated lipolysis with age or under pathological conditions may contribute to neurodegenerative processes by limiting the availability of fatty acids for beta-oxidation or membrane synthesis. ### Key Experiment: To test Hypothesis 1, a multi-modal approach could be employed. Initially, single-nucleus RNA sequencing (snRNA-seq) could be performed on epicardial adipose tissue biopsies from patients with and without coronary artery disease. This would quantify [LIPE](/details-gene/3991) expression levels specifically within the [epicardial adipocyte](/details-cell/CL1000309) population and correlate them with disease status. For functional validation, primary human [epicardial adipocytes](/details-cell/CL1000309) could be isolated and cultured. [LIPE](/details-gene/3991) expression could then be silenced using shRNA, followed by stimulation with catecholamines to mimic stress. The resulting changes in the secretome, particularly the profile of released fatty acids and pro-inflammatory cytokines, could be measured by mass spectrometry and ELISA, respectively, to directly link [LIPE](/details-gene/3991) activity to paracrine signaling. ### Therapeutic Potential: As a critical enzyme controlling the rate-limiting step of lipolysis, [LIPE](/details-gene/3991) represents a compelling therapeutic target for metabolic diseases. Given that loss-of-function mutations are associated with an increased risk of type 2 diabetes ([Link](https://doi.org/10.1056/nejmoa1315496)), strategies involving the **activation** of [LIPE](/details-gene/3991) could be beneficial. Small-molecule activators could potentially improve lipid profiles and enhance insulin sensitivity by promoting the efficient breakdown of stored triglycerides. Conversely, in conditions characterized by excessive lipolysis and fatty acid toxicity (lipo-toxicity), targeted **inhibition** might be a viable strategy. The development of tissue-specific modulators would be ideal to avoid systemic side effects, making [LIPE](/details-gene/3991) a high-priority target for drug discovery programs in metabolic medicine.

Genular Protein ID: 3427804119

Symbol: LIPS_HUMAN

Name: Hormone-sensitive lipase

UniProtKB Accession Codes:

Q05469 Q3LRT2 Q6NSL7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 80 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 4 EMBL 4 ESTHER 1 Ensembl 1 ExpressionAtlas 1 GO 18 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 Rhea 29 SABIO-RK 1 SIGNOR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8506334

Title: Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium.

PubMed ID: 8506334

DOI: 10.1073/pnas.90.11.4897

PubMed ID: 8812477

Title: Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase.

PubMed ID: 8812477

DOI: 10.1006/geno.1996.0383

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15955102

Title: Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase.

PubMed ID: 15955102

DOI: 10.1111/j.0022-202x.2005.23761.x

PubMed ID: 15716583

Title: Continuous monitoring of cholesterol oleate hydrolysis by hormone-sensitive lipase and other cholesterol esterases.

PubMed ID: 15716583

DOI: 10.1194/jlr.m400509-jlr200

PubMed ID: 17026959

Title: Association and insulin regulated translocation of hormone-sensitive lipase with PTRF.

PubMed ID: 17026959

DOI: 10.1016/j.bbrc.2006.09.094

PubMed ID: 16803459

Title: Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes; segregation of specific proteins and functions.

PubMed ID: 16803459

DOI: 10.1111/j.1742-4658.2006.05345.x

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 19800417

Title: In vitro stereoselective hydrolysis of diacylglycerols by hormone-sensitive lipase.

PubMed ID: 19800417

DOI: 10.1016/j.bbalip.2009.09.020

PubMed ID: 24848981

Title: Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes.

PubMed ID: 24848981

DOI: 10.1056/nejmoa1315496

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 1076
  • Mass: 116598
  • Checksum: 1CC0E3880FF64D74
  • Sequence:
    • MEPGSKSVSR SDWQPEPHQR PITPLEPGPE KTPIAQPESK TLQGSNTQQK PASNQRPLTQ 
QETPAQHDAE SQKEPRAQQK SASQEEFLAP QKPAPQQSPY IQRVLLTQQE AASQQGPGLG 
KESITQQEPA LRQRHVAQPG PGPGEPPPAQ QEAESTPAAQ AKPGAKREPS APTESTSQET 
PEQSDKQTTP VQGAKSKQGS LTELGFLTKL QELSIQRSAL EWKALSEWVT DSESESDVGS 
SSDTDSPATM GGMVAQGVKL GFKGKSGYKV MSGYSGTSPH EKTSARNHRH YQDTASRLIH 
NMDLRTMTQS LVTLAEDNIA FFSSQGPGET AQRLSGVFAG VREQALGLEP ALGRLLGVAH 
LFDLDPETPA NGYRSLVHTA RCCLAHLLHK SRYVASNRRS IFFRTSHNLA ELEAYLAALT 
QLRALVYYAQ RLLVTNRPGV LFFEGDEGLT ADFLREYVTL HKGCFYGRCL GFQFTPAIRP 
FLQTISIGLV SFGEHYKRNE TGLSVAASSL FTSGRFAIDP ELRGAEFERI TQNLDVHFWK 
AFWNITEMEV LSSLANMASA TVRVSRLLSL PPEAFEMPLT ADPTLTVTIS PPLAHTGPGP 
VLVRLISYDL REGQDSEELS SLIKSNGQRS LELWPRPQQA PRSRSLIVHF HGGGFVAQTS 
RSHEPYLKSW AQELGAPIIS IDYSLAPEAP FPRALEECFF AYCWAIKHCA LLGSTGERIC 
LAGDSAGGNL CFTVALRAAA YGVRVPDGIM AAYPATMLQP AASPSRLLSL MDPLLPLSVL 
SKCVSAYAGA KTEDHSNSDQ KALGMMGLVR RDTALLLRDF RLGASSWLNS FLELSGRKSQ 
KMSEPIAEPM RRSVSEAALA QPQGPLGTDS LKNLTLRDLS LRGNSETSSD TPEMSLSAET 
LSPSTPSDVN FLLPPEDAGE EAEAKNELSP MDRGLGVRAA FPEGFHPRRS SQGATQMPLY 
SSPIVKNPFM SPLLAPDSML KSLPPVHIVA CALDPMLDDS VMLARRLRNL GQPVTLRVVE 
DLPHGFLTLA ALCRETRQAA ELCVERIRLV LTPPAGAGPS GETGAAGVDG GCGGRH

Genular Protein ID: 3436950947

Symbol: A8K8W7_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K8W7

Database IDs:

ARBA 38 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 80 DNASU 1 DisGeNET 1 EC 4 EMBL 2 ESTHER 1 GO 9 Gene3D 1 InterPro 5 KEGG 1 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 4 RefSeq 1 Rhea 29 SAM 1 SUPFAM 1 UniPathway 1

Sequence Information:

  • Length: 1076
  • Mass: 116584
  • Checksum: 01AF00E31ABF8CCA
  • Sequence:
    • MEPGSKSVSR SDWQPEPHQR PITPLEPGPE KTPIAQPESK TLQGSNTQQK PASNQRPLTQ 
QETPAQHDAE SQKEPRAQQK SASQEEFLAP QKPAPQQSPY VQRVLLTQQE AASQQGPGLG 
KESITQQEPA LRQRHVAQPG PGPGEPPPAQ QEAESTPAAQ AKPGAKREPS APTESTSQET 
PEQSDKQTTP VQGAKSKQGS LTELGFLTKL QELSIQRSAL EWKALSEWVT DSESESDVGS 
SSDTDSPATM GGMVAQGVKL GFKGKSGYKV MSGYSGTSPH EKTSARNHRH YQDTASRLIH 
NMDLRTMTQS LVTLAEDNIA FFSSQGPGET AQRLSGVFAG VREQALGLEP ALGRLLGVAH 
LFDLDPETPA NGYRSLVHTA RCCLAHLLHK SRYVASNRRS IFFRTSHNLA ELEAYLAALT 
QLRALVYYAQ RLLVTNRPGV LFFEGDEGLT ADFLREYVTL HKGCFYGRCL GFQFTPAIRP 
FLQTISIGLV SFGEHYKRNE TGLSVAASSL FTSGRFAIDP ELRGAEFERI TQNLDVHFWK 
AFWNITEMEV LSSLANMASA TVRVSRLLSL PPEAFEMPLT ADPTLTVTIS PPLAHTGPGP 
VLVRLISYDL REGQDSEELS SLIKSNGQRS LELWPRPQQA PRSRSLIVHF HGGGFVAQTS 
RSHEPYLKSW AQELGAPIIS IDYSLAPEAP FPRALEECFF AYCWAIKHCA LLGSTGERIC 
LAGDSAGGNL CFTVALRAAA YGVRVPDGIM AAYPATMLQP AASPSRLLSL MDPLLPLSVL 
SKCVSAYAGA KTEDHSNSDQ KALGMMGLVR RDTALLLRDF RLGASSWLNS FLELSGRKSQ 
KMSEPIAEPM RRSVSEAALA QPQGPLGTDS LKNLTLRDLS LRGNSETSSD TPEMSLSAET 
LSPSTPSDVN FLLPPEDAGE EAEAKNELSP MDRGLGVRAA FPEGFHPRRS SQGATQMPLY 
SSPIVKNPFM SPLLAPDSML KSLPPVHIVA CALDPMLDDS VMLARRLRNL GQPVTLRVVE 
DLPHGFLTLA ALCRETRQAA ELCVERIRLV LTPPAGAGPS GETGAAGVDG GCGGRH