Human Gene PNPLA2 (ENST00000336615.9) from GENCODE V44
  Description: Homo sapiens patatin like phospholipase domain containing 2 (PNPLA2), mRNA. (from RefSeq NM_020376)
RefSeq Summary (NM_020376): This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010].
Gencode Transcript: ENST00000336615.9
Gencode Gene: ENSG00000177666.17
Transcript (Including UTRs)
   Position: hg38 chr11:818,914-825,573 Size: 6,660 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg38 chr11:819,719-824,862 Size: 5,144 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:818,914-825,573)mRNA (may differ from genome)Protein (504 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PLPL2_HUMAN
DESCRIPTION: RecName: Full=Patatin-like phospholipase domain-containing protein 2; EC=3.1.1.3; AltName: Full=Adipose triglyceride lipase; AltName: Full=Calcium-independent phospholipase A2; AltName: Full=Desnutrin; AltName: Full=IPLA2-zeta; AltName: Full=Pigment epithelium-derived factor; AltName: Full=TTS2.2; AltName: Full=Transport-secretion protein 2; Short=TTS2;
FUNCTION: Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets. Also has acylglycerol transacylase activity. May act coordinately with LIPE/HLS within the lipolytic cascade. Regulates adiposome size and may be involved in the degradation of adiposomes. May play an important role in energy homeostasis. May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion.
CATALYTIC ACTIVITY: Triacylglycerol + H(2)O = diacylglycerol + a carboxylate.
ENZYME REGULATION: Inhibited by BEL ((E)-6-(bromomethylene)-3-(1- naphthalenyl)-2H-tetrahydropyran-2-one), a suicide substrate inhibitor. No differences in enzymatic activity that uses (1,2- dilinoleoyl)-phosphatidylcholine as substrate was detected in the presence or absence of ATP. Activated by ABHD5 and SERPINF1.
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.5 with (1,2-dilinoleoyl)-phosphatidylcholine as substrate;
PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
SUBUNIT: Interacts with ABHD5; this association stimulates PNPLA2 triglyceride hydrolase activity (By similarity). Interacts with SERPINF1; interacts at one site of interaction. Despite a colocalization in lipid droplets, it probably does not interact with PLIN (By similarity).
SUBCELLULAR LOCATION: Lipid droplet. Cell membrane; Single-pass type II membrane protein.
TISSUE SPECIFICITY: Highest expression in adipose tissue. Also detected in heart, skeletal muscle, and portions of the gastrointestinal tract. Detected in normal retina and retinoblastoma cells. Detected in retinal pigment epithelium and, at lower intensity, in the inner segments of photoreceptors and in the ganglion cell layer of the neural retina (at protein level).
DEVELOPMENTAL STAGE: Induced during differentiation of primary preadipocytes to adipocytes. Expression increased from fetal to adult in retinal pigment epithelium.
POLYMORPHISM: Genetic variations in PNPLA2 may be associated with plasma free fatty acids, triglycerides levels, and fasting glucose concentrations.
DISEASE: Note=Genetic variations in PNPLA2 may be associated with risk of diabetes mellitus type 2.
DISEASE: Defects in PNPLA2 are the cause of neutral lipid storage disease with myopathy (NLSDM) [MIM:610717]; also known as neutral lipid storage disease without ichthyosis. NSLDM is a neutral lipid storage disorder (NLSD) with myopathy but without ichthyosis. NLSDs are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Individuals with NLSDM did not show obesity, in spite of a defect in triglyceride degradation in fibroblasts and in marked triglyceride storage in liver, muscles, and other visceral cells.
SIMILARITY: Contains 1 patatin domain.
SEQUENCE CAUTION: Sequence=AAP34448.1; Type=Frameshift; Positions=501; Sequence=CAC01131.1; Type=Erroneous initiation; Sequence=CAC01132.1; Type=Erroneous initiation;

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: PNPLA2
Diseases sorted by gene-association score: neutral lipid storage disease with myopathy* (1702), lipid storage disease (57), chanarin-dorfman syndrome (20), myopathy (7), infantile neuroaxonal dystrophy 1 (7), obesity (4), diabetes mellitus, noninsulin-dependent (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 463.08 RPKM in Adipose - Visceral (Omentum)
Total median expression: 3889.75 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -89.90190-0.473 Picture PostScript Text
3' UTR -253.90711-0.357 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016035 - Acyl_Trfase/lysoPLipase
IPR002641 - Patatin/PLipase_A2-rel

Pfam Domains:
PF01734 - Patatin-like phospholipase

ModBase Predicted Comparative 3D Structure on Q96AD5
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserNo orthologGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGI EnsemblEnsembl  
Protein Sequence Protein SequenceProtein Sequence  
Alignment AlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004465 lipoprotein lipase activity
GO:0004806 triglyceride lipase activity
GO:0016411 acylglycerol O-acyltransferase activity
GO:0016787 hydrolase activity

Biological Process:
GO:0006629 lipid metabolic process
GO:0008152 metabolic process
GO:0010891 negative regulation of sequestering of triglyceride
GO:0010898 positive regulation of triglyceride catabolic process
GO:0016042 lipid catabolic process
GO:0019433 triglyceride catabolic process
GO:0019915 lipid storage
GO:0034389 lipid particle organization
GO:0036155 acylglycerol acyl-chain remodeling
GO:0043687 post-translational protein modification
GO:0044242 cellular lipid catabolic process
GO:0044267 cellular protein metabolic process
GO:0055088 lipid homeostasis

Cellular Component:
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005788 endoplasmic reticulum lumen
GO:0005789 endoplasmic reticulum membrane
GO:0005811 lipid particle
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  HQ651812 - Homo sapiens patatin-like phospholipase domain containing 2 (PNPLA2) mRNA, complete cds.
JF279441 - Homo sapiens nonfunctional patatin-like phospholipase domain containing protein 2 (ATGL) mRNA, complete sequence.
JF279442 - Homo sapiens patatin-like phospholipase domain containing protein 2 (ATGL) mRNA, complete cds.
KF601369 - Homo sapiens patatin-like phospholipase domain-containing protein 2 (PNPLA2) mRNA, complete cds.
BC017280 - Homo sapiens patatin-like phospholipase domain containing 2, mRNA (cDNA clone MGC:29650 IMAGE:4875483), complete cds.
LF207970 - JP 2014500723-A/15473: Polycomb-Associated Non-Coding RNAs.
MA443547 - JP 2018138019-A/15473: Polycomb-Associated Non-Coding RNAs.
AK308435 - Homo sapiens cDNA, FLJ98383.
AJ278475 - Homo sapiens partial mRNA for transport-secretion protein 2.1 (TTS-2.1 gene).
AJ278476 - Homo sapiens partial mRNA for transport-secretion protein 2.2, (TTS-2.2 gene).
AB527798 - Synthetic construct DNA, clone: pF1KB5911, Homo sapiens PNPLA2 gene for patatin-like phospholipase domain containing protein 2, without stop codon, in Flexi system.
CU677897 - Synthetic construct Homo sapiens gateway clone IMAGE:100019710 5' read PNPLA2 mRNA.
KU139129 - Homo sapiens nonfunctional patatin-like phospholipase domain containing 2 variant (PNPLA2) mRNA, complete sequence.
KJ899303 - Synthetic construct Homo sapiens clone ccsbBroadEn_08697 PNPLA2 gene, encodes complete protein.
AY894804 - Homo sapiens adipose triglyceride lipase (ATGL) mRNA, complete cds.
KF833264 - Homo sapiens patatin-like phospholipase domain-containing protein 2 (PNPLA2) mRNA, complete cds.
KF833265 - Homo sapiens patatin-like phospholipase domain-containing protein 2 (PNPLA2) mRNA, complete cds.
KU139128 - Homo sapiens patatin-like phospholipase domain containing 2 variant (PNPLA2) mRNA, complete cds.
AY203925 - Homo sapiens FP17548 mRNA, complete cds.
JD020468 - Sequence 1492 from Patent EP1572962.
JD033789 - Sequence 14813 from Patent EP1572962.
AF055000 - Homo sapiens clone 24519 unknown mRNA, partial cds.
BC011958 - Homo sapiens patatin-like phospholipase domain containing 2, mRNA (cDNA clone IMAGE:4158010), partial cds.
JD023883 - Sequence 4907 from Patent EP1572962.
JD036253 - Sequence 17277 from Patent EP1572962.
LF370577 - JP 2014500723-A/178080: Polycomb-Associated Non-Coding RNAs.
MA606154 - JP 2018138019-A/178080: Polycomb-Associated Non-Coding RNAs.
AL833707 - Homo sapiens mRNA; cDNA DKFZp667M109 (from clone DKFZp667M109).
LF370578 - JP 2014500723-A/178081: Polycomb-Associated Non-Coding RNAs.
MA606155 - JP 2018138019-A/178081: Polycomb-Associated Non-Coding RNAs.
LF370579 - JP 2014500723-A/178082: Polycomb-Associated Non-Coding RNAs.
MA606156 - JP 2018138019-A/178082: Polycomb-Associated Non-Coding RNAs.
JD206009 - Sequence 187033 from Patent EP1572962.
JD051037 - Sequence 32061 from Patent EP1572962.
JD129413 - Sequence 110437 from Patent EP1572962.
JD282224 - Sequence 263248 from Patent EP1572962.
JD391410 - Sequence 372434 from Patent EP1572962.
JD394366 - Sequence 375390 from Patent EP1572962.
JD394017 - Sequence 375041 from Patent EP1572962.
JD400114 - Sequence 381138 from Patent EP1572962.
LF370580 - JP 2014500723-A/178083: Polycomb-Associated Non-Coding RNAs.
MA606157 - JP 2018138019-A/178083: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
LIPAS-PWY - triacylglycerol degradation

Reactome (by CSHL, EBI, and GO)

Protein Q96AD5 (Reactome details) participates in the following event(s):

R-HSA-1482647 2-MAG and DAG are transacylated to TAG by PNPLA2/3
R-HSA-1482654 2-MAG is transacylated to DAG by PNPLA2/3
R-HSA-1482811 DAG is hydrolyzed to 2-MAG by PNPLA2/3
R-HSA-1482777 TAG is hydrolyzed to DAG by PNPLA2/3
R-HSA-8952289 FAM20C phosphorylates FAM20C substrates
R-HSA-1482883 Acyl chain remodeling of DAG and TAG
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-1483206 Glycerophospholipid biosynthesis
R-HSA-392499 Metabolism of proteins
R-HSA-597592 Post-translational protein modification
R-HSA-1483257 Phospholipid metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ATGL, ENST00000336615.1, ENST00000336615.2, ENST00000336615.3, ENST00000336615.4, ENST00000336615.5, ENST00000336615.6, ENST00000336615.7, ENST00000336615.8, FP17548, NM_020376, O60643, PLPL2_HUMAN, Q5EFF5, Q6XYE5, Q96AD5, Q96ET6, Q9NQ61, Q9NQ62, uc001lrt.1, uc001lrt.2, uc001lrt.3, uc001lrt.4, uc001lrt.5
UCSC ID: ENST00000336615.9
RefSeq Accession: NM_020376
Protein: Q96AD5 (aka PLPL2_HUMAN)
CCDS: CCDS7718.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.