MGLL (Monoacylglycerol Lipase) - Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the MGLL gene, encoding monoacylglycerol lipase, including genomic context, expression, mutations, and disease associations.
Gene Information Card
| Symbol | MGLL |
|---|---|
| Full Name | Monoglyceride lipase |
| Gene Type | protein coding |
| Chromosomal Location | 3q21.3 |
| NCBI Gene ID | 11343 ncbi.nlm.nih.gov/gene/11343 |
| Ensembl ID | ENSG00000074416 |
| UniProt ID | Q99685 |
| OMIM ID | 609699 |
| HGNC ID | 17038 |
| Aliases | MGL, HU-K5, MAGL, DAGL, HUG-K5 |
Description
The MGLL gene encodes monoacylglycerol lipase (MAGL), a serine hydrolase that catalyzes the hydrolysis of monoacylglycerides to free fatty acids and glycerol. It is a key enzyme in the endocannabinoid system, degrading the major endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL also plays a role in lipid metabolism, inflammation, and cancer progression. Its expression is widespread, with high levels in adipose tissue, brain, and liver. MGLL has been implicated in various diseases, including cancer, neurological disorders, and metabolic conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | MGLL overexpression promotes tumor growth and metastasis by increasing free fatty acids and modulating lipid signaling pathways. | Multiple studies (e.g., in colorectal, prostate, and ovarian cancers) show elevated MGLL expression correlates with poor prognosis. |
| Neurodegenerative diseases (e.g., Alzheimer's disease) | Altered endocannabinoid signaling due to MGLL activity may contribute to neuroinflammation and neurodegeneration. | Preclinical models show MGLL inhibition reduces neuroinflammation and amyloid pathology. |
| Metabolic syndrome / obesity | MGLL regulates lipolysis in adipose tissue; altered expression affects energy homeostasis and insulin sensitivity. | Genetic variants and expression changes are associated with obesity and type 2 diabetes. |
| Inflammatory disorders | MGLL modulates inflammatory responses via 2-AG and prostaglandin synthesis. | Inhibition of MGLL reduces inflammation in animal models of colitis and arthritis. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | High | High expression in subcutaneous and visceral fat. |
| Brain | High | Particularly in cortex, hippocampus, and cerebellum. |
| Liver | Moderate | Hepatocytes express MGLL. |
| Lung | Low | Low expression in normal lung. |
| Kidney | Low | Minimal expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | Moderate | Cervical cancer cell line. |
| HepG2 | High | Hepatocellular carcinoma cell line. |
| SH-SY5Y | High | Neuroblastoma cell line. |
| MCF7 | Low | Breast cancer cell line. |
| A549 | Moderate | Lung carcinoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.485C>T (p.Pro162Leu) | Missense | Rare (MAF <0.01) | May affect enzyme activity; clinical significance unknown. |
| c.1000G>A (p.Val334Ile) | Missense | Rare | Potential impact on protein stability. |
| c.1145A>G (p.Asn382Ser) | Missense | Rare | Reported in cancer samples; functional impact not characterized. |
| c.1264C>T (p.Arg422Trp) | Missense | Rare | Located in catalytic domain; may reduce activity. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MGLL are rare and not well characterized. Some missense variants may reduce catalytic activity, but no definitive pathogenic loss-of-function mutations have been reported in inherited diseases.
Gain of Function (GOF)
Gain-of-function mutations have not been described. Overexpression (not mutation) is the primary mechanism in cancer.
Dominant Negative (DN)
No dominant-negative mutations have been reported for MGLL.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endocannabinoid signaling
• Glycerolipid metabolism
• Fatty acid degradation
• Prostaglandin synthesis (via arachidonic acid release)
Protein Summary
Monoacylglycerol lipase (MAGL) is a 33 kDa serine hydrolase composed of 313 amino acids. It belongs to the alpha/beta hydrolase fold family. The enzyme contains a catalytic triad (Ser122, His272, Asp239) and is primarily localized in the cytoplasm and membrane. MAGL hydrolyzes monoacylglycerols, including 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid, thereby regulating endocannabinoid tone. It also plays a role in the degradation of dietary fats and in the mobilization of arachidonic acid for prostaglandin synthesis. MAGL is a target for therapeutic intervention in pain, inflammation, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MGLL Knockout HEK293 Cell Line | EDJ-KQ3014 | Human | 11343 | Details Get a Quote |
| MGLL Knockout A-549 Cell Line | EDJ-KQ24221 | Human | 11343 | Details Get a Quote |
| MGLL Knockout HCT 116 Cell Line | EDJ-KQ24222 | Human | 11343 | Details Get a Quote |
| MGLL Knockout HeLa Cell Line | EDJ-KQ24223 | Human | 11343 | Details Get a Quote |
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