DAGLA: Diacylglycerol Lipase Alpha
Key enzyme in endocannabinoid signaling and neuroinflammation
Gene Information Card
| Symbol | DAGLA |
|---|---|
| Full Name | Diacylglycerol Lipase Alpha |
| Gene Type | Protein-coding |
| Chromosomal Location | 11q12.2 |
| NCBI Gene ID | 7471 ncbi.nlm.nih.gov/gene/7471 |
| Ensembl ID | ENSG00000134780 |
| UniProt ID | Q9Y4D2 |
| OMIM ID | 614395 |
| HGNC ID | 2896 |
| Aliases | DAGLALPHA, C11orf11, DAGL1, DGL-ALPHA, NSGAT2 |
Description
DAGLA encodes diacylglycerol lipase alpha, a membrane-bound enzyme that catalyzes the hydrolysis of diacylglycerol to produce 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid in the central nervous system. DAGLA is primarily expressed in the brain and plays a critical role in retrograde synaptic signaling, neuroinflammation, and pain modulation. Mutations in DAGLA are associated with early-onset epileptic encephalopathy and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Early-onset epileptic encephalopathy | Loss-of-function mutations impair 2-AG synthesis, disrupting synaptic homeostasis and leading to hyperexcitability | PMID: 31028174, ClinVar |
| Neurodevelopmental disorder with hypotonia and seizures | Biallelic DAGLA variants reduce enzyme activity, affecting endocannabinoid-mediated neurotransmission | PMID: 31028174 |
| Spastic paraplegia (rare) | Missense mutations alter catalytic domain, decreasing 2-AG production and impairing motor neuron function | PMID: 31028174 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Cerebellum | 15.2 | High |
| Hippocampus | 14.8 | High |
| Spinal cord | 8.3 | Medium |
| Testis | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.2 | Neuronal model |
| U-87 MG (glioblastoma) | 7.8 | Glial expression |
| HEK293 (embryonic kidney) | 0.3 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2062C>T (p.Arg688*) | Nonsense | Rare | Loss of function; truncation of catalytic domain |
| c.1487G>A (p.Arg496Gln) | Missense | Rare | Reduced enzyme activity; associated with epilepsy |
| c.1699C>T (p.Arg567Trp) | Missense | Rare | Impaired 2-AG production; neurodevelopmental phenotype |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish DAGLA catalytic activity, leading to decreased 2-AG levels and impaired endocannabinoid signaling.
Gain of Function (GOF)
Not reported in DAGLA.
Dominant Negative (DN)
Not reported in DAGLA.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endocannabinoid signaling (Reactome R-HSA-373753)
• 2-arachidonoylglycerol biosynthesis (Reactome R-HSA-428930)
• Glycerophospholipid metabolism (KEGG hsa00564)
Protein Summary
DAGLA is a 1,042-amino acid integral membrane protein localized to the plasma membrane and intracellular membranes. It contains a conserved serine-lipase motif (GXSXG) essential for catalytic activity. The enzyme preferentially hydrolyzes sn-1 acyl chains of diacylglycerol to generate 2-AG. DAGLA is the primary source of 2-AG in the brain and is essential for retrograde synaptic suppression. Its activity is regulated by calcium and protein-protein interactions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DAGLA Knockout HEK293 Cell Line | EDJ-KQ4176 | Human | 747 | Details Get a Quote |
| DAGLA Knockout A-549 Cell Line | EDJ-KQ25293 | Human | 747 | Details Get a Quote |
| DAGLA Knockout HCT 116 Cell Line | EDJ-KQ26619 | Human | 747 | Details Get a Quote |
| DAGLA Knockout HeLa Cell Line | EDJ-KQ26620 | Human | 747 | Details Get a Quote |
