Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

LIPE (lipase E, hormone sensitive type)

Written2018-02Seher Gök
Scientific and Research Council of TURKEY, Ankara, Turkey;

Abstract Review on LIPE, with data on DNA, on the protein encoded and where the gene is implicated

Keywords LIPE; hormone sensitive lipase

(Note : for Links provided by Atlas : click)


Alias (NCBI)lipase
HGNC Alias symbHSL
HGNC Previous namelipase, hormone-sensitive
LocusID (NCBI) 3991
Atlas_Id 43466
Location The human LIPE gene is located on 19q13.2 [Link to chromosome band 19q13]  [Link to chromosome band 19q13]
Location_base_pair Starts at 42401514 and ends at 42427388 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping LIPE.png]
Local_order LIPE spans 25,920bp, starts at 42401507 and ends at 42427426 bp from pter (according to hg38-Dec_2013).
  Figure 1. Gene neighbours of LIPE on chromosome 19q13.2 (NCBI Annotation Release 108)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


Description Orientation: Minus strand; 25,920 bases; Exon count: 31 (NCBI Homo sapiens Annotation Release 108) (Table 1).
Table 1.     31 Exons and their locations for LIPE (from Ensembl)
Gene Id  Exon IdChromosome Strand Exon Start  Exon End
ENSG00000079435  ENSE00001194800  19-42401507  42402075
ENSG00000079435  ENSE00003091115  19-42401816  42402075
ENSG00000079435  ENSE00003004228  19-42402037  42402075
ENSG00000079435  ENSE00003029968  19-42402607  42403055
ENSG00000079435  ENSE00000709262  19-42402607  42403031
ENSG00000079435  ENSE00003099674  19-42402673  42403031
ENSG00000079435  ENSE00000709260  19-42405385  42405561
ENSG00000079435  ENSE00003199240  19-42405385  42405837
ENSG00000079435  ENSE00003007563  19-42406161  42406319
ENSG00000079435  ENSE00000709257  19-42406161  42406388
ENSG00000079435  ENSE00003076590  19-42407174  42407226
ENSG00000079435  ENSE00000709254  19-42407174  42407468
ENSG00000079435  ENSE00003124417  19-42407400  42407468
ENSG00000079435  ENSE00003630092  19-42407606  42407791
ENSG00000079435  ENSE00003654406  19-42407606  42407791
ENSG00000079435  ENSE00003603624  19-42407976  42408121
ENSG00000079435  ENSE00003477031  19-42407976  42408121
ENSG00000079435  ENSE00003202428  19-42408087  42408121
ENSG00000079435  ENSE00003018018  19-42408095  42408121
ENSG00000079435  ENSE00003693446  19-42408232  42408322
ENSG00000079435  ENSE00003608280  19-42408232  42408322
ENSG00000079435  ENSE00003146825  19-42408311  42408322
ENSG00000079435  ENSE00003530964  19-42410307  42410842
ENSG00000079435  ENSE00003532609  19-42410307  42410842
ENSG00000079435  ENSE00003170038  19-42410582  42410842
ENSG00000079435  ENSE00003219943  19-42412274  42412347
ENSG00000079435  ENSE00003155428  19-42412365  42412448
ENSG00000079435  ENSE00003063620  19-42422993  42423222
ENSG00000079435  ENSE00003095994  19-42422993  42423203
ENSG00000079435  ENSE00003221897  19-42423419  42424123
ENSG00000079435  ENSE00001162583  19-42426267  42427426
Transcription Human LIPE gene has 9 transcripts (Table 2).
Table 2.     Transcripts of human LIPE gene (Ensembl annotation Release 85)
Name  Transcript ID  bp  Translation ID  Protein  Biotype
LIPE-201  ENST00000244289.8  3813  ENSP00000244289  1076aa  Protein coding
LIPE-205  ENST00000599783.5  1367  ENSP00000469990  260aa  Protein coding
LIPE-203  ENST00000597620.5  915  ENST00000597620  305aa  Protein coding
LIPE-206  ENST00000599918.1  824  ENST00000599918  275aa  Protein coding
LIPE-202  ENST00000597001.1  759  ENSP00000469268  176aa  Protein coding
LIPE-204  ENST00000599211.1  738  ENSP00000472531  222aa  Protein coding
LIPE-208  ENST00000601189.1  335  ENSP00000469030  80aa  Protein coding
LIPE-209  ENST00000602000.1  722  _  No protein  Processed transcript
LIPE-207  ENST00000600224.1  812  _  No Protein  Retained intron 
Pseudogene LOC106780900 hormone-sensitive lipase pseudogene [Equus caballus (horse)] (NCBI Equus caballus Annotation Release 103)


Note LIPE plays a crucial role in acylglycerol and cholesteryl ester hydrolysis in adipose tissue and exhibits cholesterol hydrolase activity in steroidogenic tissue and macrophages.
Description LIPE is highly expressed in adipose tissue as well as in heart and skeletal muscle, pancreatic β-cells, placenta, adrenal glands, ovary and testis (Haemmerle et al., 2003). 2 isoforms produced by alternative splicing (Yeamen et, al., 2004; Holst et al., 1996). Isoform 1 : Testicular form also known as canonical sequence, composed of 1,076 amino acids, has 116,598 Da molecular mass.
Two testicular forms of LIPE have been characterized (Stenson et al., 1996 ; Mairal et al., 2002). The 3.9 kb mRNA encodes a 1,076 amino acid protein that contains a unique NH2-terminal region encoded by exon T1. The 3.3 kb mRNA encodes a protein that is identical to the adipocyte LIPE form. However, the mRNA species differ in their 5' ends. Exon usage is mutually exclusive; exon T2 is only transcribed in testis, and exon B is only transcribed in Adipose tissue (Lucas et al., 2003).
Isoform 2 : Adipocyte form, composed of 775 amino acids encoded by 9 exons, has 84,128 Da molecular mass.
  Figure 2. Genomic organization of the LIPE gene coding sequences (red boxes) and untranslated regions (grey boxes). Exons T1 and T2 are used in testis. Exons A and B are used in the colon adenocarcinoma cell line HT29 and adipose tissue, respectively. Exons 1 to 9 are used in all tissues expressing LIPE (adapted from Lucas et al., 2003).
Expression A 3.3-kb transcript was detected in mammary gland, adrenal gland, adipose tissue and muscle, and both a 3.3 and 3.9 kb transcripts were found in testis (Holst et al. 1996). RNA-seq data from 95 human individuals representing 27 different tissues reveal biased expression in fat and testis (BioProject: PRJEB4337) (Figure 2).
  Figure 3. LIPE tissue expression. RNA-seq data from 27 tissues are reported as mean RPKM (Reads Per Kilobase Million), corresponding to mean values of the different individual samples from each tissue type.
Localisation Found in cell membrane (UniProtKB-SubCell), cytosol (HPA), lipid droplet (UniProtKB-SubCell) and high density caveolae (UniProtKB-SubCell). Translocates to the cytoplasm from the caveolae upon insulin stimulation for lipolysis activation (Egan et al., 1992).
Function Hormone sensitive lipase is a lipolytic enzyme of the 'GDXG' family catalyzing the rate limiting step of diacylglycerol and monoacylglycerol lipolysis (Stralfors et al., 1978). 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. LIPE is a multifunctional enzyme catalyzing (GO_REF:0000003);
Diacylglycerol + H2O = monoacylglycerol + a carboxylate.
Triacylglycerol + H2O = diacylglycerol + a carboxylate.
Monoacylglycerol + H2O = glycerol + a carboxylate.
Enzyme is regulated post-transcriptionally. LIPE is rapidly activated by cAMP-dependent phosphorylation under the influence of catecholamines. Dephosphorylation and inactivation via protein phosphatases or inhibition of protein kinases, are controlled by insulin (Yeamen et al., 1994). Ser 659 and Ser 660 have been shown as phosphorylation sites, for in vitro activation of LIPE (Anthonsen et al., 1998).
Also it has protein binding and protein kinase binding function interacting selectively and non-covalently with any protein of protein complex (Aboulaich et al., 2006).
Homology LIPE gene is conserved in chimpanzee, dog, cow, mouse, rat, zebrafish and frog (Table 3).
Table 3.    Pairwise alignment of LIPE gene and protein sequences (in distance from human) 
GeneIdentity %
H. SapiensLIPE
vs. P.troglodytesLIPE99.099.3
vs. C.lupusLIPE80.284.0
vs. B.taurusLIPE85.986.2
vs. M.musculusLipe84.382.0
vs. R.norvegicusLipe74.978.1
vs. X.tropicalislipe62.762.3
vs. D.rerirolipeb61.761.5


Note 198 missense, 12 truncating and 2 inframe mutations of LIPE (cBioPortal).
  Figure 4. Mutation types observed in LIPE expression in literature and corresponding color codes are as follows: Green: Missense Mutations, Black: Truncating Mutations: Nonsense, Nonstop, Frameshift deletion, Frameshift insertion, Splice site, Brown: Inframe Mutations: Inframe deletion, Inframe insertion, Purple: Other Mutations: All other types of mutations
Somatic LIPE has 3543 SNPs (Ensembl).
Arg 309 Cyc polymorphism is associated with an increased serum cholesterol levels and type 2 diabetes (Shimada et al. 1996).
LIPE i6(CA)n repeat polymorphism is associated with type 2 diabetes and obesity (Magré et al. 1998). The C-60 G polymorphism is located in the promoter region of the LIPE and it is possible that the substitution of C with G nucleotide result in a decrease in gene expression (Talmud et al. 2001). The C-60 G polymorphism in the promoter of LIPE is associated with body composition and waist circumference (Garenc et al. 2002; Carlsson et al. 2006). In addition, the C-60 G allele male carriers present lower levels of fasting non-esterified fatty acid and higher levels of low density lipoprotein cholesterol (Talmud et al. 2001).

Implicated in

Entity Lipodystrophy, Familial Partial, 6 (FPLD6)
Disease A 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 (OMIM:615980).
Cytogenetics Autosomal recessive. Caused by homozygous mutation in the LIPE gene. Genomewide autozygosity mapping and whole-exome sequencing, identified homozygosity for a 2bp insertion in the LIPE gene (Farhan et al. 2014). The mutation caused a frameshift within the hormone-sensitive lipase domain predicted to result in a premature termination codon with an approximately 50% loss of the original polypeptide.
Entity Non-alcoholic Fatty Liver Disease (NAFLD)
Disease NAFLD, defined as hepatic steatosis with an intrahepatic triglyceride (TG) content?>?5% of the liver volume or weight, develops owing to an imbalance between fatty acid (FA) input and output.
Cytogenetics In glucose intolerance state, LIPE promoter (CC + GG) contributed the greatest impact on raising serum triglyceride followed by fatty liver and Adipose insulin resistance (Hsiao et al., 2013).
Entity Multiple Symmetric Lipomatosis
Disease Rare condition characterized by the symmetric growth of fatty tumors (lipomas) around the neck, shoulders, upper arms and/or upper trunk. It most often affects men of mediterranean ancestry between the ages of 30 and 70 who have a history of alcohol abuse. The signs and symptoms vary greatly from person to person. Usually, accumulation of fatty tissue increases over time and may lead to a loss of neck mobility and pain. The lipomas can cause physical deformity and peripheral neuropathy, when they compress a nerve.
Cytogenetics Exome sequencing identified a novel homozygous NC_000019.9:g.42906092C>A variant on chromosome 19, leading to a NM_005357.3:c.3103G>T nucleotide change in coding DNA and corresponding p.(Glu1035*) protein change in LIPE gene as the disease-causing variant (Zolotov et al., 2017).
Entity Various Cancers
Note LIPE gene expression is altered in number of cancers.
Cytogenetics Search in cBioPortal showed that LIPE is altered in 461 (1.1%) of 40567 sequenced cases / patients (Figure 5).


Association and insulin regulated translocation of hormone-sensitive lipase with PTRF.
Aboulaich N., Ortegren U., Vener A.V., Strïlfors P.
2006; Biochem. Biophys. Res. Commun., 350, 657 - 661.
PMID 17026959
Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro
Anthonsen, M. W., L. Rönnstrand, C. Wernstedt, E. Degerman, C. Holm.
1998; ? J. Biol. Chem. 273: 215-221
PMID 9417067
The hormone-sensitive lipase C-60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects.
Carlsson, E., Johansson, L.E., Ström, K., Hoffstedt, J., Groop, L., Holm, C., Ridderstrïle, M.
2006; Int J Obes (Lond) 30:1442-1448.
PMID 16534522
Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet.
Egan, J. J., A. S. Greenberg, M-K. Chang, S. A. Wek, J. M. C. Moos, C. Londos.
1992; Proc. Natl. Acad. Sci., 89:8537-8541.
PMID 1528859
A novel LIPE nonsense mutation found using exome sequencing in siblings with late-onset familial partial lipodystrophy.
Farhan, S. M. K., Robinson, J. F., McIntyre, A. D., Marrosu, M. G., Ticca, A. F., Loddo, S., Carboni, N., Brancati, F., Hegele, R. A.
2014; Canad. J. Cardiol. 30: 1649-1654
PMID 25475467
The hormone-sensitive lipase gene and body composition: the HERITAGE Family Study
Garenc, C., Pérusse, L., Chagnon, Y.C., Rankinen, T., Gagnon, J., Borecki, I.B.
2002; Int J Obes Relat Metab Disord 26:220-227.
PMID 11850754
Letting lipids go: Hormone-sensitive lipase
Haemmerle G., Zimmermann R., Zechner R.
2003; Current Opinion in Lipidology, 14, 289-297.
PMID 12840660
Risk interaction of obesity, insulin resistance and hormone-sensitive lipase promoter polymorphisms (LIPE-60 C > G) in the development of fatty liver.
Hsiao, P.-J., Chen, Z.-C., Hung, W.-W., Yang, Y.-H. C., Lee, M.-Y., Huang, J.-F., & Kuo, K.-K.
2013; BMC Medical Genetics, 14, 54
PMID 23688034
Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis.
Lucas S, Tavernier G, Tiraby C, Mairal A, Langin D.
2003; J Lipid Res. 44(1):154-63.
PMID 12518034
Characterization of a novel testicular form of human hormone-sensitive lipase.
Mairal, A., N. Melaine, H. Laurell, J. Grober, L. Stenson Holst, T. Guillaudeux, C. Holm, B. Jégou, D. Langin.
2002; Biochem. Biophys. Res. Commun. 291: 286-290.
PMID 11846402
Detection of an amino acid polymorphism in hormone-sensitive lipase in Japanese subjects.
Shimada, F., Makino, H., Hashimoto, N., Iwaoka, H., Taira, M., Nozaki, O.
1996; Metabolism 45:862-864
PMID 8692022
Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase.
Stenson Holst, L., D. Langin, H. Mulder, H. Laurell, J. Grober, A. Bergh, H. W. Mohrenweiser, G. Edgren, C. Holm.
1996; Genomics, 35: 441-447.
PMID 8812477
Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study
Talmud, P.J., Palmen, J., Luan, J., Flavell, D., Byrne, C.D., Waterworth, D.M.
2001; Biochim Biophys Acta 29:239-244
PMID 11731226
The multifunctional role of hormone-sensitive lipase in lipid metabolism
Yeaman, S. J., Smith, G. M., Jepson, C. A., Wood, S. L., Emmison, N.
1994; Adv. Enzyme Regul. 34, 355-370
PMID 7942281
Homozygous LIPE mutation in siblings with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy.
Zolotov S, Xing C, Mahamid R, Shalata A, Sheikh-Ahmad M, Garg A
2017; Am J Med Genet A. Jan;173(1):190-194.
PMID 27862896


This paper should be referenced as such :
Seher Gk
LIPE (lipase E, hormone sensitive type)
Atlas Genet Cytogenet Oncol Haematol. 2018;22(10):423-428.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)LIPE   6621
Entrez_Gene (NCBI)LIPE    lipase E, hormone sensitive type
AliasesAOMS4; FPLD6; HSL; LHS; 
GeneCards (Weizmann)LIPE
Ensembl hg19 (Hinxton)ENSG00000079435 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000079435 [Gene_View]  ENSG00000079435 [Sequence]  chr19:42401514-42427388 [Contig_View]  LIPE [Vega]
ICGC DataPortalENSG00000079435
Genatlas (Paris)LIPE
SOURCE (Princeton)LIPE
Genetics Home Reference (NIH)LIPE
Genomic and cartography
GoldenPath hg38 (UCSC)LIPE  -     chr19:42401514-42427388 -  19q13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)LIPE  -     19q13.2   [Description]    (hg19-Feb_2009)
GoldenPathLIPE - 19q13.2 [CytoView hg19]  LIPE - 19q13.2 [CytoView hg38]
Genome Data Viewer NCBILIPE [Mapview hg19]  
OMIM151750   615980   
Gene and transcription
Genbank (Entrez)AK292482 AK309893 BC029301 BC029961 BC070041
RefSeq transcript (Entrez)NM_005357
Consensus coding sequences : CCDS (NCBI)LIPE
Gene ExpressionLIPE [ NCBI-GEO ]   LIPE [ EBI - ARRAY_EXPRESS ]   LIPE [ SEEK ]   LIPE [ MEM ]
Gene Expression Viewer (FireBrowse)LIPE [ Firebrowse - Broad ]
GenevisibleExpression of LIPE in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3991
GTEX Portal (Tissue expression)LIPE
Human Protein AtlasENSG00000079435-LIPE [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ05469   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ05469  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ05469
Domaine pattern : Prosite (Expaxy)LIPASE_GDXG_HIS (PS01173)    LIPASE_GDXG_SER (PS01174)   
Domains : Interpro (EBI)AB_hydrolase    AB_hydrolase_3    HSL_N    Lipase_GDXG_HIS_AS    Lipase_GDXG_put_SER_AS   
Domain families : Pfam (Sanger)Abhydrolase_3 (PF07859)    HSL_N (PF06350)   
Domain families : Pfam (NCBI)pfam07859    pfam06350   
Conserved Domain (NCBI)LIPE
AlphaFold pdb e-kbQ05469   
Human Protein Atlas [tissue]ENSG00000079435-LIPE [tissue]
Protein Interaction databases
IntAct (EBI)Q05469
Ontologies - Pathways
Ontology : AmiGOsterol esterase activity  triglyceride lipase activity  protein binding  lipid droplet  cytosol  caveola  protein phosphorylation  cholesterol metabolic process  membrane  lipid catabolic process  triglyceride catabolic process  hormone-sensitive lipase activity  retinol metabolic process  diacylglycerol catabolic process  ether lipid metabolic process  acylglycerol lipase activity  all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity  retinyl-palmitate esterase activity  1,3-diacylglycerol acylhydrolase activity  1,2-diacylglycerol acylhydrolase activity  
Ontology : EGO-EBIsterol esterase activity  triglyceride lipase activity  protein binding  lipid droplet  cytosol  caveola  protein phosphorylation  cholesterol metabolic process  membrane  lipid catabolic process  triglyceride catabolic process  hormone-sensitive lipase activity  retinol metabolic process  diacylglycerol catabolic process  ether lipid metabolic process  acylglycerol lipase activity  all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity  retinyl-palmitate esterase activity  1,3-diacylglycerol acylhydrolase activity  1,2-diacylglycerol acylhydrolase activity  
Pathways : KEGGInsulin signaling pathway   
REACTOMEQ05469 [protein]
REACTOME PathwaysR-HSA-163560 [pathway]   
NDEx NetworkLIPE
Atlas of Cancer Signalling NetworkLIPE
Wikipedia pathwaysLIPE
Orthology - Evolution
GeneTree (enSembl)ENSG00000079435
Phylogenetic Trees/Animal Genes : TreeFamLIPE
Homologs : HomoloGeneLIPE
Homology/Alignments : Family Browser (UCSC)LIPE
Gene fusions - Rearrangements
Fusion : FusionGDB3.1.1.79   
Fusion : QuiverLIPE
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerLIPE [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LIPE
Exome Variant ServerLIPE
GNOMAD BrowserENSG00000079435
Varsome BrowserLIPE
ACMGLIPE variants
Genomic Variants (DGV)LIPE [DGVbeta]
DECIPHERLIPE [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisLIPE 
ICGC Data PortalLIPE 
TCGA Data PortalLIPE 
Broad Tumor PortalLIPE
OASIS PortalLIPE [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICLIPE  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DLIPE
Mutations and Diseases : HGMDLIPE
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)LIPE
DoCM (Curated mutations)LIPE
CIViC (Clinical Interpretations of Variants in Cancer)LIPE
NCG (London)LIPE
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM151750    615980   
Genetic Testing Registry LIPE
NextProtQ05469 [Medical]
Target ValidationLIPE
Huge Navigator LIPE [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDLIPE
Pharm GKB GenePA30393
Clinical trialLIPE
DataMed IndexLIPE
PubMed105 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:21:18 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us