PNPLA2 (Patatin-Like Phospholipase Domain Containing 2)
Key regulator of intracellular lipolysis; mutations cause neutral lipid storage disease with myopathy (NLSDM).
Gene Information Card
| Symbol | PNPLA2 |
|---|---|
| Full Name | Patatin-like phospholipase domain containing 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 57104 ncbi.nlm.nih.gov/gene/57104 |
| Ensembl ID | ENSG00000177666 |
| UniProt ID | Q96AD5 |
| OMIM ID | 609059 |
| HGNC ID | 18502 |
| Aliases | ATGL, TTS-2.2, iPLA2zeta, FP17548 |
Description
The PNPLA2 gene encodes adipose triglyceride lipase (ATGL), a key enzyme that catalyzes the first step of triglyceride hydrolysis in adipose tissue and other tissues. It plays a central role in lipolysis, providing free fatty acids for energy production. Mutations in PNPLA2 lead to neutral lipid storage disease with myopathy (NLSDM), characterized by excessive triglyceride accumulation in multiple tissues, particularly skeletal muscle, heart, and liver.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neutral lipid storage disease with myopathy (NLSDM) | Loss-of-function mutations in PNPLA2 impair ATGL enzymatic activity, leading to defective triglyceride hydrolysis and accumulation of lipid droplets in non-adipose tissues. | Multiple case reports and functional studies; ClinVar lists pathogenic variants. |
| Cardiomyopathy (associated with NLSDM) | Lipid accumulation in cardiac myocytes due to ATGL deficiency causes cardiac dysfunction. | Clinical observations in NLSDM patients; OMIM #609059. |
| Hepatic steatosis (associated with NLSDM) | Reduced hepatic lipolysis leads to triglyceride accumulation in hepatocytes. | Reported in NLSDM patients; functional studies in animal models. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | High | Highest expression |
| Skeletal muscle | Moderate | Significant expression |
| Heart | Moderate | Cardiac muscle |
| Liver | Low | Lower expression |
| Testis | Low | Detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Adipocytes | High | Primary site of lipolysis |
| Hepatocytes | Low | Minor role in liver |
| Myocytes | Moderate | Skeletal and cardiac muscle |
| Macrophages | Low | Detected in some studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.757+1G>A (splice site) | Splice mutation | Rare | Loss of function; causes NLSDM |
| p.Leu114Pro | Missense | Rare | Loss of function; reduced enzymatic activity |
| p.Arg299Cys | Missense | Rare | Loss of function; associated with NLSDM |
| c.475-2A>G (splice acceptor) | Splice mutation | Rare | Loss of function; causes NLSDM |
Mutation functional classification
Loss of Function (LOF)
Most PNPLA2 mutations are loss-of-function, leading to reduced or absent ATGL activity, causing lipid accumulation and NLSDM.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PNPLA2.
Dominant Negative (DN)
No dominant-negative effects have been described; PNPLA2 mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004806 - triglyceride lipase activity | • GO:0016298 - lipase activity |
| • GO:0006629 - lipid metabolic process | • GO:0016042 - lipid catabolic process |
| • GO:0005737 - cytoplasm | • GO:0005811 - lipid droplet |
Pathways
• Triglyceride catabolism
• Lipolysis in adipocytes
• Fatty acid metabolism
Protein Summary
Adipose triglyceride lipase (ATGL) is a 504-amino acid protein that belongs to the patatin-like phospholipase family. It contains an N-terminal patatin domain with a catalytic serine-aspartate dyad. ATGL specifically hydrolyzes the first ester bond of triglycerides, releasing free fatty acids and diacylglycerol. Its activity is regulated by cofactors such as CGI-58 (ABHD5) and inhibitors like G0S2. ATGL is predominantly expressed in adipose tissue but also in muscle, heart, and other tissues, where it contributes to intracellular lipolysis and energy homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PNPLA2 Knockout HEK293 Cell Line | EDJ-KQ3484 | Human | 57104 | Details Get a Quote |
| PNPLA2 Knockout A-549 Cell Line | EDJ-KQ25260 | Human | 57104 | Details Get a Quote |
| PNPLA2 Knockout HCT 116 Cell Line | EDJ-KQ25261 | Human | 57104 | Details Get a Quote |
| PNPLA2 Knockout HeLa Cell Line | EDJ-KQ25262 | Human | 57104 | Details Get a Quote |
| PNPLA2 Knockdown HEK293 Stable Cell Line | EDJ-KD003 | Human | 57104 | Details Get a Quote |
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