ABHD6 (Abhydrolase Domain Containing 6) Gene
A key regulator of endocannabinoid signaling and lipid metabolism, implicated in neurological and metabolic disorders.
Gene Information Card
| Symbol | ABHD6 |
|---|---|
| Full Name | Abhydrolase domain containing 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p14.3 |
| NCBI Gene ID | 57406 ncbi.nlm.nih.gov/gene/57406 |
| Ensembl ID | ENSG00000163686 |
| UniProt ID | Q9BV23 |
| OMIM ID | 616120 |
| HGNC ID | 21396 |
| Aliases | 2-AG hydrolase, FLJ31234, MGC10744 |
Description
ABHD6 (abhydrolase domain containing 6) encodes a member of the serine hydrolase superfamily. The encoded enzyme is a membrane-associated alpha/beta hydrolase that primarily functions as a 2-arachidonoylglycerol (2-AG) hydrolase, thereby regulating endocannabinoid signaling. It is also involved in the metabolism of other lipid esters and plays roles in various cellular processes including insulin secretion, neuroinflammation, and cancer progression. ABHD6 is expressed in multiple tissues, with high levels in the brain, liver, and adipose tissue.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity and metabolic syndrome | ABHD6 regulates 2-AG levels in adipose tissue and liver, influencing insulin sensitivity and energy metabolism. Altered expression or activity may contribute to metabolic dysregulation. | PubMed: 27162256; 28842488 |
| Neuroinflammation and neurodegenerative diseases | ABHD6 modulates 2-AG levels in the brain, affecting neuroinflammatory responses. Inhibition of ABHD6 has been shown to reduce neuroinflammation in models of multiple sclerosis and Alzheimer's disease. | PubMed: 26043716; 29377010 |
| Epilepsy | ABHD6 inhibition elevates 2-AG levels, which can reduce seizure severity in animal models. Genetic variants may influence susceptibility. | PubMed: 24501175 |
| Cancer (e.g., colorectal, breast) | ABHD6 expression is altered in several cancers, and its activity affects tumor cell proliferation and migration via lipid signaling pathways. | PubMed: 28842488; 31235858 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.9 | Medium |
| Liver | 7.2 | Medium |
| Adipose tissue | 6.5 | Low |
| Pancreas | 5.8 | Low |
| Kidney | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 12.5 | High expression |
| SH-SY5Y (neuroblastoma) | 9.8 | Moderate expression |
| MCF7 (breast cancer) | 7.3 | Moderate expression |
| A549 (lung cancer) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs11140490 (intronic) | SNV | ~30% (global) | Associated with altered ABHD6 expression in some studies; functional significance unclear. |
| rs11762213 (missense, p.Val129Ile) | SNV | ~5% (European) | May affect enzyme activity; clinical significance not established. |
| c.1-? (promoter variants) | Regulatory | Rare | Potentially affect transcription; not well characterized. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ABHD6 are rare and not well documented in human disease. In animal models, knockout leads to increased 2-AG levels and altered metabolic phenotypes.
Gain of Function (GOF)
Gain-of-function mutations have not been reported. Overexpression in cell lines can increase 2-AG hydrolysis, but no pathogenic gain-of-function variants are known.
Dominant Negative (DN)
No dominant-negative mutations have been described for ABHD6.
View complete mutation data：
Gene Ontology (GO)
| • hydrolase activity | • serine hydrolase activity |
| • 2-arachidonoylglycerol hydrolase activity | • lipid metabolic process |
| • endocannabinoid signaling pathway | • membrane |
Pathways
• Endocannabinoid signaling
• Glycerolipid metabolism
• Fatty acid metabolism
Protein Summary
The ABHD6 protein is a 337-amino acid single-pass type II membrane protein localized to the endoplasmic reticulum and plasma membrane. It contains an alpha/beta hydrolase fold with a catalytic Ser-His-Asp triad. ABHD6 hydrolyzes 2-arachidonoylglycerol (2-AG) to arachidonic acid and glycerol, thereby terminating endocannabinoid signaling. It also exhibits lysophosphatidylinositol lipase activity. The protein is expressed in multiple tissues and is involved in regulating insulin secretion, neuroinflammation, and cancer cell proliferation. Its structure has been partially resolved, and selective inhibitors are being developed for therapeutic applications.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABHD6 Knockout HEK293 Cell Line | EDJ-KQ2213 | Human | 57406 | Details Get a Quote |
| ABHD6 Knockout A-549 Cell Line | EDJ-KQ22471 | Human | 57406 | Details Get a Quote |
| ABHD6 Knockout HCT 116 Cell Line | EDJ-KQ22472 | Human | 57406 | Details Get a Quote |
| ABHD6 Knockout HeLa Cell Line | EDJ-KQ22473 | Human | 57406 | Details Get a Quote |
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