ABHD6 Gene

HGNC Family	Abhydrolase domain containing (ABHD)
Name	abhydrolase domain containing 6
Description	Enables monoacylglycerol lipase activity. Involved in acylglycerol catabolic process. Predicted to be located in late endosome membrane and lysosomal membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in GABA-ergic synapse; glutamatergic synapse; and postsynaptic membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ABHD6 is an α/β‐hydrolase that plays multifaceted roles in lipid signaling by acting as a monoacylglycerol lipase with distinct substrate specificity and subcellular localization. In the central nervous system, ABHD6 contributes to the hydrolysis of the endocannabinoid 2–arachidonoylglycerol (2–AG), thereby regulating localized endocannabinoid pools that control synaptic plasticity and neuronal signaling without fully overlapping with the activities of monoacylglycerol lipase (MAGL) or ABHD12."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In immune cells such as macrophages, ABHD6 modulates 2–AG levels to direct downstream formation of bioactive lipids (for example, the anti‐inflammatory prostaglandin D2–glycerol ester) and fine‐tunes inflammatory responses without eliciting the central side effects observed with broader 2–AG hydrolysis inhibition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside the brain, ABHD6 plays an important role in peripheral energy metabolism. In pancreatic β–cells, for instance, its activity limits the accumulation of lipolysis–derived monoacylglycerols that otherwise bind and activate proteins involved in insulin granule exocytosis, making ABHD6 a negative modulator of glucose–stimulated insulin secretion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in metabolic tissues, ABHD6 influences lipid homeostasis and energy balance, and its inhibition has been shown to protect against diet–induced obesity and insulin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n ABHD6 also appears to regulate synaptic function beyond endocannabinoid metabolism. It can modulate the trafficking and surface expression of AMPA receptors, thereby attenuating excitatory neurotransmission through a mechanism that is independent of its catalytic hydrolase activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, substrate profiling studies reveal that ABHD6 shows a preference for specific monoacylglycerol species over others, underscoring its role in segregating lipid pools within cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its classical role in 2–AG hydrolysis, ABHD6 degrades other lipid substrates such as bis(monoacylglycerol)phosphate (BMP) in hepatic tissues—a function that links it to lysosomal lipid sorting and overall glycerophospholipid metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, the distinct spatial distribution and substrate selectivity of ABHD6 enable it to fine–tune both endocannabinoid and broader lipid signaling networks in the brain and peripheral tissues, highlighting its potential as a therapeutic target in neurological, inflammatory, and metabolic disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jacqueline L Blankman, Gabriel M Simon, Benjamin F Cravatt "}, {"type": "b", "children": [{"type": "t", "text": "A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chem Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chembiol.2007.11.006"}], "href": "https://doi.org/10.1016/j.chembiol.2007.11.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18096503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18096503"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "William R Marrs, Jacqueline L Blankman, Eric A Horne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn.2601"}], "href": "https://doi.org/10.1038/nn.2601"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20657592"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20657592"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mireille Alhouayek, Julien Masquelier, Patrice D Cani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1314017110"}], "href": "https://doi.org/10.1073/pnas.1314017110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24101490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24101490"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shangang Zhao, Yves Mugabo, Jose Iglesias, et al. "}, {"type": "b", "children": [{"type": "t", "text": "α/β-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2014.04.003"}], "href": "https://doi.org/10.1016/j.cmet.2014.04.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24814481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24814481"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gwynneth Thomas, Jenna L Betters, Caleb C Lord, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The serine hydrolase ABHD6 Is a critical regulator of the metabolic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2013.08.047"}], "href": "https://doi.org/10.1016/j.celrep.2013.08.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24095738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24095738"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mengping Wei, Jian Zhang, Moye Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "α/β-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1524589113"}], "href": "https://doi.org/10.1073/pnas.1524589113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27114538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27114538"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Dina Navia-Paldanius, Juha R Savinainen, Jarmo T Laitinen "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M030411"}], "href": "https://doi.org/10.1194/jlr.M030411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22969151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22969151"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Maria A Pribasnig, Irina Mrak, Gernot F Grabner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "α/β Hydrolase Domain-containing 6 (ABHD6) Degrades the Late Endosomal/Lysosomal Lipid Bis(monoacylglycero)phosphate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.669168"}], "href": "https://doi.org/10.1074/jbc.M115.669168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26491015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26491015"}]}]}]}
Proteins	ABHD6_HUMAN
NCBI Gene ID	57406
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ABHD6 has 6,110 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for ABHD6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ABHD6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ABHD6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ABHD6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ABHD6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ABHD6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ABHD6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ABHD6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ABHD6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ABHD6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ABHD6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ABHD6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ABHD6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ABHD6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ABHD6 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ABHD6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ABHD6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ABHD6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ABHD6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ABHD6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ABHD6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ABHD6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ABHD6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ABHD6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ABHD6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ABHD6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ABHD6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ABHD6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ABHD6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ABHD6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ABHD6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ABHD6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ABHD6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ABHD6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ABHD6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ABHD6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ABHD6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing ABHD6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ABHD6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ABHD6 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing ABHD6 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ABHD6 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.