ABHD6

Summary

ABHD6 (abhydrolase domain containing 6, acylglycerol lipase, HGNC:21398) is a protein-coding gene on chromosome 3p14.3, encoding Monoacylglycerol lipase ABHD6 (Q9BV23). Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol.

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.

Source: NCBI Gene 57406 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 60 total — 4 pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001320126

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21398
Approved symbol	ABHD6
Name	abhydrolase domain containing 6, acylglycerol lipase
Location	3p14.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163686
Ensembl biotype	protein_coding
OMIM	616966
Entrez	57406

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 22 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000295962, ENST00000463756, ENST00000470440, ENST00000475982, ENST00000478253, ENST00000480457, ENST00000485900, ENST00000857888, ENST00000857889, ENST00000857890, ENST00000857891, ENST00000857892, ENST00000857893, ENST00000857894, ENST00000857895, ENST00000857896, ENST00000857897, ENST00000857898, ENST00000857899, ENST00000857900, ENST00000857901, ENST00000857902, ENST00000972008, ENST00000972009, ENST00000972010

RefSeq mRNA: 2 — MANE Select: NM_001320126 NM_001320126, NM_020676

CCDS: CCDS2887

Canonical transcript exons

ENST00000478253 — 10 exons

Exon	Start	End
ENSE00001077312	58269321	58269434
ENSE00001077315	58274658	58274815
ENSE00001077318	58285085	58285139
ENSE00001077320	58270932	58271064
ENSE00001122420	58256562	58256705
ENSE00001169338	58285353	58285453
ENSE00001843804	58237792	58237916
ENSE00001848712	58249878	58249942
ENSE00001864865	58293589	58294734
ENSE00003548897	58267189	58267345

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 94.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9626 / max 509.7179, expressed in 1648 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37030	4.6529	1458
37027	2.1024	1089
37028	1.9950	493
37031	0.1530	65
37029	0.0593	19

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	94.86	gold quality
jejunal mucosa	UBERON:0000399	94.25	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.61	gold quality
corpus callosum	UBERON:0002336	93.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.41	gold quality
endothelial cell	CL:0000115	91.96	gold quality
cerebellar vermis	UBERON:0004720	91.88	gold quality
spinal cord	UBERON:0002240	91.65	gold quality
right lobe of liver	UBERON:0001114	91.38	gold quality
duodenum	UBERON:0002114	91.34	gold quality
lateral globus pallidus	UBERON:0002476	91.07	gold quality
inferior vagus X ganglion	UBERON:0005363	91.02	gold quality
prefrontal cortex	UBERON:0000451	90.88	gold quality
cortical plate	UBERON:0005343	90.39	gold quality
Ammon’s horn	UBERON:0001954	90.13	gold quality
subthalamic nucleus	UBERON:0001906	90.10	gold quality
liver	UBERON:0002107	90.06	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.00	gold quality
cerebellar cortex	UBERON:0002129	89.70	gold quality
cerebellar hemisphere	UBERON:0002245	89.62	gold quality
cerebellum	UBERON:0002037	89.53	gold quality
adrenal tissue	UBERON:0018303	89.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.28	gold quality
spleen	UBERON:0002106	89.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.82	gold quality
frontal cortex	UBERON:0001870	88.81	gold quality
frontal lobe	UBERON:0016525	88.81	gold quality
adenohypophysis	UBERON:0002196	88.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting ABHD6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-125A-5P	99.36	70.59	1640

Literature-anchored findings (GeneRIF, showing 12)

• report the tissue distribution, subcellular location and differential distribution among cancer cell lines of Abhd6, one unannotated member of this group (PMID:18360779)
• High expression of ABHD6 in Ewing family tumors (EFT) in comparison to normal tissues and other tumors suggests that ABHD6 might be an interesting new diagnostic or therapeutic target for EFT. (PMID:19793082)
• ABHD6 increases from neonatal age. (PMID:22827915)
• Data show that the three hydrolases are genuine MAG lipases; medium-chain saturated MAGs were the best substrates for hABHD6 and hMAGL, whereas hABHD12 preferred the 1 (3)- and 2-isomers of arachidonoylglycerol. (PMID:22969151)
• Results confirm the genetic association of the locus 3p14.3 with systemic lupus erythematosus in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. (PMID:24534757)
• data suggest that ABHD6 controls BMP catabolism and is therefore part of the late endosomal/lysosomal lipid-sorting machinery (PMID:26491015)
• The hydrolase activity of ABHD6 was not required for the effects of ABHD6 on AMPAR function in either neurons or transfected HEK293T cells. Thus, these findings reveal a novel and unexpected mechanism governing AMPAR trafficking at synapses through ABHD6. (PMID:27114538)
• Data suggest that ABHD6 plays important role in regulation of signaling via monoacylglycerols (MAGs) in both central and peripheral tissues; alterations in MAG signaling are involved in type 2 diabetes, obesity, and metabolic syndrome. [REVIEW] (PMID:28880480)
• We discovered a regulatory role of ABHD6 in human plasmacytoid dendritic cells (pDCs) through modulating the local abundance of its substrate, the endocannabinoid 2-arachidonyl glycerol (2-AG), and elucidated a hitherto unknown cannabinoid receptor 2-mediated regulatory role of 2-AG on IFN-alpha induction by pDCs. (PMID:30728209)
• It demonstrate that ABHD6 affect Bis(monoacylglycerol)phosphate (BMP) metabolism in mice and humans. (PMID:30894461)
• Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis. (PMID:32143183)
• ABHD6 suppresses colorectal cancer progression via AKT signaling pathway. (PMID:38197491)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	abhd6a	ENSDARG00000060756
danio_rerio	abhd6b	ENSDARG00000070894
mus_musculus	Abhd6	ENSMUSG00000025277
rattus_norvegicus	Abhd6	ENSRNOG00000008167
drosophila_melanogaster	kraken	FBGN0020545
caenorhabditis_elegans	abhd-11.1	WBGENE00009316

Paralogs (12): ABHD5 (ENSG00000011198), ABHD4 (ENSG00000100439), EPHX3 (ENSG00000105131), ABHD11 (ENSG00000106077), MEST (ENSG00000106484), ABHD14B (ENSG00000114779), EPHX2 (ENSG00000120915), ABHD8 (ENSG00000127220), BPHL (ENSG00000137274), EPHX4 (ENSG00000172031), SERHL2 (ENSG00000183569), ABHD14A (ENSG00000248487)

Protein

Protein identifiers

Monoacylglycerol lipase ABHD6 — Q9BV23 (reviewed: Q9BV23)

Alternative names: 2-arachidonoylglycerol hydrolase, Abhydrolase domain-containing protein 6

All UniProt accessions (4): Q9BV23, C9J010, C9JNE7, F8WBP4

UniProt curated annotations — full annotation on UniProt →

Function. Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol. Through 2-arachidonoylglycerol degradation may regulate endocannabinoid signaling pathways. Also has a lysophosphatidyl lipase activity with a preference for lysophosphatidylglycerol among other lysophospholipids. Also able to degrade bis(monoacylglycero)phosphate (BMP) and constitutes the major enzyme for BMP catabolism. BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes and lysosomes and plays a key role in the formation of intraluminal vesicles and in lipid sorting.

Subcellular location. Late endosome membrane. Lysosome membrane. Mitochondrion membrane.

Similarity. Belongs to the AB hydrolase superfamily.

RefSeq proteins (2): NP_001307055, NP_065727 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR000639	Epox_hydrolase-like	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050266	AB_hydrolase_sf	Family

Pfam: PF00561

Catalyzed reactions (Rhea), 12 shown:

• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:26132)
• 1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38487)
• 2-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38491)
• 2-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+) (RHEA:39963)
• 1-tetradecanoylglycerol + H2O = tetradecanoate + glycerol + H(+) (RHEA:44312)
• 1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+) (RHEA:44316)
• 1-decanoylglycerol + H2O = decanoate + glycerol + H(+) (RHEA:44320)
• 1-octanoylglycerol + H2O = octanoate + glycerol + H(+) (RHEA:44328)
• 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:44728)
• 2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+) (RHEA:44732)
• 1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+) (RHEA:48428)
• 3-(9Z-octadecenoyl)-sn-glycero-1-phospho-(3’-(9Z-octadecenoyl)-1’-sn-glycerol) + H2O = 3-(9Z-octadecenoyl)-sn-glycero-1-phospho-(1’-sn-glycerol) + (9Z)-octadecenoate + H(+) (RHEA:55712)

UniProt features (47 total): helix 17, strand 9, sequence variant 5, binding site 3, active site 3, topological domain 2, sequence conflict 2, turn 2, chain 1, mutagenesis site 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7OTS	X-RAY DIFFRACTION	1.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV23-F1	90.99	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 148 (nucleophile); 278 (charge relay system); 306 (charge relay system)

Ligand- & substrate-binding residues (3): 306; 80; 149

Mutagenesis-validated functional residues (1):

Position	Phenotype
148	loss of 2-arachidonoyglycerol hydrolase activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-426048	Arachidonate production from DAG
R-HSA-109582	Hemostasis
R-HSA-114508	Effects of PIP2 hydrolysis
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-416476	G alpha (q) signalling events
R-HSA-76002	Platelet activation, signaling and aggregation

MSigDB gene sets: 254 (showing top): GCM_MAP4K4, AAGCAAT_MIR137, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GCM_PTPRD, GOCC_VACUOLAR_MEMBRANE, PEREZ_TP63_TARGETS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING

GO Biological Process (12): phospholipid catabolic process (GO:0009395), arachidonate metabolic process (GO:0019369), negative regulation of cell migration (GO:0030336), acylglycerol catabolic process (GO:0046464), positive regulation of lipid biosynthetic process (GO:0046889), monoacylglycerol catabolic process (GO:0052651), long-term synaptic depression (GO:0060292), regulation of retrograde trans-synaptic signaling by endocanabinoid (GO:0099178), negative regulation of cold-induced thermogenesis (GO:0120163), regulation of endocannabinoid signaling pathway (GO:2000124), lysobisphosphatidic acid metabolic process (GO:2001311), lipid metabolic process (GO:0006629)

GO Molecular Function (5): glycerophospholipase activity (GO:0004620), monoacylglycerol lipase activity (GO:0047372), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), membrane (GO:0016020), late endosome membrane (GO:0031902), mitochondrial membrane (GO:0031966), AMPA glutamate receptor complex (GO:0032281), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), mitochondrion (GO:0005739), lysosome (GO:0005764), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Effects of PIP2 hydrolysis	1
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Signal Transduction	1
Signaling by GPCR	1
GPCR downstream signalling	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	2
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
acylglycerol metabolic process	1
neutral lipid catabolic process	1
glycerolipid catabolic process	1
lipid biosynthetic process	1
positive regulation of biosynthetic process	1
positive regulation of lipid metabolic process	1
regulation of lipid biosynthetic process	1
monoacylglycerol metabolic process	1
acylglycerol catabolic process	1
regulation of synaptic plasticity	1
negative regulation of synaptic transmission	1
retrograde trans-synaptic signaling by endocannabinoid	1
regulation of trans-synaptic signaling	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
regulation of G protein-coupled receptor signaling pathway	1
endocannabinoid signaling pathway	1
glycerophospholipid metabolic process	1
alditol phosphate metabolic process	1
primary metabolic process	1
phospholipase activity	1
lipase activity	1
carboxylic ester hydrolase activity	1
molecular_function	1
binding	1
catalytic activity	1
lysosome	1
lytic vacuole membrane	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABHD6	ABHD12	Q8N2K0	918
ABHD6	MGLL	Q99685	895
ABHD6	FAAH	O00519	882
ABHD6	DAGLA	Q9Y4D2	827
ABHD6	NAPEPLD	Q6IQ20	812
ABHD6	DAGLB	Q8NCG7	811
ABHD6	ABHD4	Q8TB40	735
ABHD6	GPR55	Q9Y2T6	717
ABHD6	ABHD16A	O95870	690
ABHD6	FAAH2	Q6GMR7	687
ABHD6	ABHD11	Q8NFV4	682
ABHD6	CNR1	P21554	671
ABHD6	NAAA	Q02083	633
ABHD6	GDE1	Q9NZC3	608
ABHD6	NCEH1	Q6PIU2	605

IntAct

35 interactions, top by confidence:

A	B	Type	Score
RTP2	ABHD6	psi-mi:“MI:0915”(physical association)	0.560
ABHD6	FIS1	psi-mi:“MI:0915”(physical association)	0.560
ABHD6	TVP23B	psi-mi:“MI:0915”(physical association)	0.560
SCAMP4	ABHD6	psi-mi:“MI:0915”(physical association)	0.560
FSHR	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
NCS1	NMT2	psi-mi:“MI:0914”(association)	0.530
ABHD6	CKMT2	psi-mi:“MI:0915”(physical association)	0.370
ABHD6	PCGF2	psi-mi:“MI:0915”(physical association)	0.370
Ufl1	PRSS1	psi-mi:“MI:0914”(association)	0.350
C5AR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
PCDHA3	ABCD4	psi-mi:“MI:0914”(association)	0.350
IGHM	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
NPTN	RTL8C	psi-mi:“MI:0914”(association)	0.350
RXFP1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
PCDHGC4		psi-mi:“MI:0914”(association)	0.350
C5AR2	UBXN8	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
OR10H2	ABCD4	psi-mi:“MI:0914”(association)	0.350
OR10H1	NRP1	psi-mi:“MI:0914”(association)	0.350
HPCA	NMT2	psi-mi:“MI:0914”(association)	0.350
HPCA	ANKRD33B	psi-mi:“MI:0914”(association)	0.350
RTP2	ABHD6	psi-mi:“MI:0915”(physical association)	0.000
FIS1	ABHD6	psi-mi:“MI:0915”(physical association)	0.000
SCAMP4	ABHD6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): ABHD6 (Affinity Capture-MS), ABHD6 (Affinity Capture-MS), ABHD6 (Affinity Capture-MS), ABHD6 (Affinity Capture-MS), ABHD6 (Affinity Capture-MS), ABHD6 (Affinity Capture-MS), TVP23B (Two-hybrid), RTP2 (Two-hybrid), FIS1 (Two-hybrid), SCAMP4 (Two-hybrid), ABHD6 (Proximity Label-MS), ABHD6 (Proximity Label-MS), ABHD6 (Affinity Capture-MS), ABHD6 (Affinity Capture-RNA), ABHD6 (Affinity Capture-MS)

ESM2 similar proteins: A2A7Z8, A7LB60, P08910, P0DKC5, P0DKC6, P22760, P70683, P83006, Q05AK6, Q0P5B7, Q13093, Q14032, Q1LZ86, Q28017, Q32LS6, Q4R2Y9, Q4V8A1, Q502J0, Q5EA42, Q5PPS7, Q5VUY0, Q5VUY2, Q5XI64, Q5ZJL8, Q5ZKL5, Q60963, Q63276, Q6DHN0, Q6GLL2, Q6IE26, Q6P093, Q7L211, Q7M370, Q7SY73, Q7Z5M8, Q802V6, Q80UX8, Q8BM81, Q8IUS5, Q8R2Y0

Diamond homologs: A0A2G0QDP0, A2BGU9, C4LA13, I6XU97, O05235, O06734, O18391, P07383, P0A573, P27747, P75311, P9WNH2, P9WNH3, Q1LZ86, Q2Y9Y7, Q54M29, Q57427, Q5ALW7, Q5QZC0, Q5XI64, Q6GLL2, Q7SY73, Q82SL8, Q8R2Y0, Q988D4, Q9BV23, Q9EPB5, Q9H4I8, Q9NQF3, A1AGT6, A7FNV8, A7ZSU1, A8A5M0, A8AQW5, A8GKT5, A8YWL3, A9MMB5, A9R4D0, B1IP53, B1JHZ5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

60 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	49
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
150826	GRCh38/hg38 3p14.3-11.1(chr3:57140424-90259960)x1	Pathogenic
253632	GRCh37/hg19 3p21.2-14.2(chr3:52086599-59689209)x1	Pathogenic
3246999	NC_000003.11:g.(?57843440)(58520833_?)del	Pathogenic
57386	GRCh38/hg38 3p21.1-14.1(chr3:54045018-66060461)x1	Pathogenic

SpliceAI

1595 predictions. Top by Δscore:

Variant	Effect	Δscore
3:58267322:GA:G	donor_gain	1.0000
3:58269319:A:AG	acceptor_gain	1.0000
3:58269320:G:GA	acceptor_gain	1.0000
3:58269320:GTTC:G	acceptor_gain	1.0000
3:58269430:ACCAG:A	donor_loss	1.0000
3:58269432:CAGG:C	donor_loss	1.0000
3:58269434:GGTAA:G	donor_loss	1.0000
3:58269435:GTAA:G	donor_loss	1.0000
3:58269436:T:A	donor_loss	1.0000
3:58270930:A:AG	acceptor_gain	1.0000
3:58270930:A:AT	acceptor_loss	1.0000
3:58270931:G:GG	acceptor_gain	1.0000
3:58270931:GTTT:G	acceptor_gain	1.0000
3:58274762:A:G	donor_gain	1.0000
3:58285138:GT:G	donor_gain	1.0000
3:58285346:T:TA	acceptor_gain	1.0000
3:58285350:A:AG	acceptor_gain	1.0000
3:58285350:AAGT:A	acceptor_gain	1.0000
3:58285351:A:G	acceptor_gain	1.0000
3:58285352:G:GG	acceptor_gain	1.0000
3:58285352:GT:G	acceptor_gain	1.0000
3:58285450:CCAGG:C	donor_loss	1.0000
3:58285454:GTAT:G	donor_loss	1.0000
3:58285455:T:G	donor_loss	1.0000
3:58267247:T:G	donor_gain	0.9900
3:58267341:TCA:T	donor_gain	0.9900
3:58267381:G:GT	donor_gain	0.9900
3:58269315:CCTCA:C	acceptor_gain	0.9900
3:58269316:CTCA:C	acceptor_gain	0.9900
3:58269317:TCAGT:T	acceptor_gain	0.9900

AlphaMissense

2223 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:58267328:T:A	W87R	0.998
3:58267328:T:C	W87R	0.998
3:58285436:T:A	W274R	0.998
3:58285436:T:C	W274R	0.998
3:58285439:G:T	G275W	0.997
3:58285448:G:C	D278H	0.997
3:58267197:G:C	R43P	0.995
3:58269354:G:C	D104H	0.995
3:58270978:G:A	G146D	0.995
3:58271002:C:A	A154D	0.995
3:58285440:G:A	G275E	0.995
3:58285449:A:C	D278A	0.995
3:58270983:T:C	S148P	0.994
3:58271057:T:G	C172W	0.994
3:58285439:G:A	G275R	0.994
3:58285439:G:C	G275R	0.994
3:58293669:C:A	H306Q	0.994
3:58293669:C:G	H306Q	0.994
3:58256642:C:G	P19R	0.993
3:58267321:G:C	K84N	0.993
3:58267321:G:T	K84N	0.993
3:58271010:T:G	Y157D	0.993
3:58285110:G:C	R236P	0.993
3:58285440:G:T	G275V	0.993
3:58285449:A:T	D278V	0.993
3:58267293:T:A	L75H	0.992
3:58267307:T:C	F80L	0.992
3:58267309:C:A	F80L	0.992
3:58267309:C:G	F80L	0.992
3:58269355:A:T	D104V	0.992

dbSNP variants (sampled 300 via entrez): RS1000003223 (3:58275685 G>A), RS1000104425 (3:58270986 A>G), RS1000111699 (3:58251720 C>G), RS1000121808 (3:58251461 C>G,T), RS1000244922 (3:58249853 GT>G), RS1000258319 (3:58288434 C>G), RS1000303427 (3:58245759 A>G), RS1000304667 (3:58240314 A>C), RS1000356744 (3:58240063 G>T), RS1000394155 (3:58258028 C>T), RS1000401319 (3:58244072 T>A,C), RS1000515950 (3:58277071 T>G), RS1000568392 (3:58275997 T>C), RS1000631400 (3:58245508 G>A), RS1000700079 (3:58250161 C>G)

Disease associations

OMIM: gene MIM:616966 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002318_144	Rheumatoid arthritis	5.000000e-08
GCST003155_45	Systemic lupus erythematosus	3.000000e-14
GCST003622_72	Systemic lupus erythematosus	5.000000e-06
GCST004603_250	Platelet count	5.000000e-15
GCST006959_32	Rheumatoid arthritis	5.000000e-08
GCST010002_426	Refractive error	5.000000e-14
GCST010083_211	Hemoglobin levels	1.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189127 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 100,377 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL175247	ORLISTAT	4	38,186
CHEMBL465	DRONABINOL	4	62,107
CHEMBL3945728	ELCUBRAGISTAT	2	84

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2-Acylglycerol ester turnover

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
KT-109	Inhibition	7.8	pIC50
WWL70	Inhibition	7.2	pIC50
WWL123	Inhibition	6.4	pIC50
SA-57	Inhibition	6.19	pIC50
ABX-1431	Inhibition	5.57	pIC50
ABD-1970	Inhibition	5.49	pIC50

ChEMBL bioactivities

179 potent at pChembl≥5 of 183 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.68	IC50	0.21	nM	CHEMBL3263579
8.89	IC50	1.3	nM	CHEMBL3263579
8.70	IC50	2	nM	CHEMBL5274434
8.60	IC50	2.512	nM	CHEMBL3906477
8.60	IC50	2.512	nM	CHEMBL3895863
8.60	IC50	2.512	nM	CHEMBL4279328
8.60	IC50	2.5	nM	CHEMBL3906477
8.60	IC50	2.5	nM	CHEMBL4279328
8.55	IC50	2.8	nM	CHEMBL3895863
8.50	IC50	3.162	nM	CHEMBL4279884
8.50	IC50	3.162	nM	CHEMBL4287766
8.44	IC50	3.6	nM	CHEMBL4581240
8.30	IC50	5.012	nM	CHEMBL4289572
8.20	IC50	6.31	nM	CHEMBL4284689
8.00	IC50	10	nM	CHEMBL4277989
7.90	IC50	12.59	nM	CHEMBL4281842
7.88	IC50	13.18	nM	ORLISTAT
7.85	IC50	14.13	nM	ORLISTAT
7.80	IC50	15.85	nM	CHEMBL4294845
7.77	IC50	17	nM	METHOXYARACHIDONOYL FLUOROPHOSPHONATE
7.70	IC50	19.95	nM	ORLISTAT
7.70	IC50	19.95	nM	CHEMBL3964338
7.60	IC50	25.12	nM	CHEMBL3970032
7.60	IC50	25.12	nM	CHEMBL4291201
7.50	IC50	31.62	nM	CHEMBL4281906
7.43	IC50	37.15	nM	ORLISTAT
7.40	IC50	39.81	nM	CHEMBL2144065
7.40	IC50	39.81	nM	CHEMBL3897587
7.40	IC50	39.81	nM	CHEMBL3931744
7.40	IC50	39.81	nM	CHEMBL3974512
7.36	IC50	43.65	nM	CHEMBL3613671
7.36	IC50	44	nM	CHEMBL3613671
7.36	IC50	44	nM	CHEMBL5284566
7.32	IC50	47.86	nM	ORLISTAT
7.32	IC50	48	nM	ORLISTAT
7.30	IC50	50.12	nM	CHEMBL3913807
7.26	IC50	55	nM	CHEMBL6035930
7.26	IC50	55	nM	CHEMBL5962440
7.26	IC50	55	nM	CHEMBL5985697
7.26	IC50	55	nM	CHEMBL5983321
7.26	IC50	55	nM	CHEMBL5782109
7.26	IC50	55	nM	CHEMBL5832448
7.26	IC50	55	nM	CHEMBL5740302
7.26	IC50	55	nM	CHEMBL5913237
7.26	IC50	55	nM	CHEMBL5949603
7.26	IC50	55	nM	CHEMBL6015117
7.26	IC50	55	nM	CHEMBL5937515
7.26	IC50	55	nM	CHEMBL5859637
7.26	IC50	55	nM	CHEMBL5788039
7.26	IC50	55	nM	CHEMBL5758154

PubChem BioAssay actives

127 with measured affinity, of 334 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
tert-butyl 3-phenyl-4-[4-[4-(trifluoromethoxy)phenyl]triazole-1-carbonyl]piperazine-1-carboxylate	1931127: Inhibition of human recombinant ABHD6	ic50	0.0020	uM
[(2R,5R)-2-benzyl-5-prop-2-ynoxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0025	uM
[(6S)-6-benzyl-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0025	uM
[(2R)-2-benzylpiperidin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0025	uM
[(2R)-2-(phenylmethoxymethyl)piperidin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0032	uM
[(3R,6S)-6-benzyl-3-hydroxy-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0032	uM
tert-butyl 3-benzyl-4-[4-[4-(trifluoromethoxy)phenyl]triazole-1-carbonyl]piperazine-1-carboxylate	1931127: Inhibition of human recombinant ABHD6	ic50	0.0036	uM
[(3R,6R)-3-hydroxy-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0050	uM
[4-(4-phenoxyphenyl)triazol-1-yl]-[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0063	uM
[(3S,6R)-3-hydroxy-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0100	uM
[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0126	uM
Orlistat	1245645: Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 10 mins by HPLC method	ic50	0.0132	uM
[4-(4-bromophenyl)triazol-1-yl]-[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0158	uM
(5Z,8Z,11Z,14Z)-1-[fluoro(methoxy)phosphoryl]icosa-5,8,11,14-tetraene	1931132: Inhibition of ABHD6 (unknown origin)	ic50	0.0170	uM
(2-benzylpiperidin-1-yl)-[4-[hydroxy(diphenyl)methyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0199	uM
(2-benzylpiperidin-1-yl)-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0251	uM
[(6R)-6-benzyl-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0251	uM
[4-(4-nitrophenyl)triazol-1-yl]-[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.0316	uM
[(2R,5R)-2-benzyl-5-(cyclopropylmethoxy)piperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0398	uM
[(3R,6S)-6-benzyl-3-hydroxy-3,6-dihydro-2H-pyridin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0398	uM
(2-benzylpiperidin-1-yl)-[4-[hydroxy(diphenyl)methyl]triazol-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0398	uM
(2-benzylpiperidin-1-yl)-[4-(4-phenylphenyl)triazol-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0398	uM
(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl) N-cyclooctyl-N-methylcarbamate	1245627: Inhibition of human ABHD6 expressed in HEK293 cells assessed as reduction in glycerol production from 1-AG hydrolysis pre-incubated for 30 mins before 1-AG substrate addition and measured 90 mins post substrate addition by fluorescence method	ic50	0.0437	uM
(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl) N-cycloheptyl-N-methylcarbamate	1931125: Inhibition of human ABHD6 expressed in HEK293 cells using 1-AG as substrate incubated for 90 mins by sensitive fluorescence glycerol assay	ic50	0.0440	uM
[(2R,5R)-2-benzyl-5-methoxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.0501	uM
[4-(4-carbamoylphenyl)phenyl] N-methyl-N-[(3-pyridin-4-ylphenyl)methyl]carbamate	1931122: Inhibition of human recombinant ABHD6 expressed in COS-7 cells in presence of FP-rhodamine labeled probe by SDS-PAGE based gel fluorescence scanning analysis	ic50	0.0700	uM
3-[(3-aminophenyl)methyl]-5-phenoxy-1,3,4-oxadiazol-2-one	1245627: Inhibition of human ABHD6 expressed in HEK293 cells assessed as reduction in glycerol production from 1-AG hydrolysis pre-incubated for 30 mins before 1-AG substrate addition and measured 90 mins post substrate addition by fluorescence method	ic50	0.0730	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[bis(1-methylindazol-5-yl)methyl]piperazine-1-carboxylate	1513559: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.0910	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[(4-methylsulfonyl-2-pyrrolidin-1-ylphenyl)methyl]piperazine-1-carboxylate	1513559: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.0990	uM
[(6S)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.1000	uM
[(2R,5S)-2-benzyl-5-methoxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.1259	uM
3-[(3-nitrophenyl)methyl]-5-phenoxy-1,3,4-oxadiazol-2-one	1245627: Inhibition of human ABHD6 expressed in HEK293 cells assessed as reduction in glycerol production from 1-AG hydrolysis pre-incubated for 30 mins before 1-AG substrate addition and measured 90 mins post substrate addition by fluorescence method	ic50	0.1300	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[(1-methyl-3-phenylpyrazol-4-yl)methyl]piperazine-1-carboxylate	1513559: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.1300	uM
[4-[hydroxy(diphenyl)methyl]triazol-2-yl]-[2-(phenoxymethyl)piperidin-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.1585	uM
[(2R,5R)-2-benzyl-5-hydroxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.1585	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-[(3-methoxyphenyl)methyl]piperidin-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.1585	uM
[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-(4-phenyltriazol-1-yl)methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.1585	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[3-(2-chlorophenyl)-1-methylpyrazol-4-yl]methyl]piperazine-1-carboxylate	1513559: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.1700	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-(dipyridin-3-ylmethyl)piperazine-1-carboxylate	1513559: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.1820	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[(4-chlorophenyl)methyl]piperazine-1-carboxylate	1513559: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.1900	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-[(4-fluorophenoxy)methyl]piperidin-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.1995	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-(phenoxymethyl)piperidin-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.1995	uM
[(2R,5S)-2-benzyl-5-hydroxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.1995	uM
3-[(3-aminophenyl)methyl]-5-methoxy-1,3,4-oxadiazol-2-one	1245627: Inhibition of human ABHD6 expressed in HEK293 cells assessed as reduction in glycerol production from 1-AG hydrolysis pre-incubated for 30 mins before 1-AG substrate addition and measured 90 mins post substrate addition by fluorescence method	ic50	0.2160	uM
[(3S,6S)-6-benzyl-3-hydroxy-3,6-dihydro-2H-pyridin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.2512	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-[(4-methoxyphenyl)methyl]piperidin-1-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.2512	uM
[2-[(4-fluorophenoxy)methyl]piperidin-1-yl]-[4-[hydroxy(diphenyl)methyl]triazol-2-yl]methanone	1339022: Inhibition of human ABHD6 using 2-AG as natural substrate by fluorescence based assay	ic50	0.2512	uM
[(2R,3R)-3-hydroxy-2-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415833: Inhibition of recombinant human ABHD6 expressed in HEK293 cells by AmplifuTM red dye based fluorescence assay	ic50	0.2512	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[2-pyrrolidin-1-yl-4-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate	1513617: Inhibition of ABHD6 in human intact PC3 cells preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.2530	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[(1-methyl-3-phenylpyrazol-5-yl)methyl]piperazine-1-carboxylate	1513559: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay	ic50	0.2900	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	7
trichostatin A	affects cotreatment, decreases expression, increases expression	4
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
Benzo(a)pyrene	increases methylation, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
methylmercuric chloride	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Antimycin A	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1

ChEMBL screening assays

50 unique, capped per target: 47 binding, 2 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209081	Binding	Inhibition of ABHD6 binding to FP-biotin in [12C][14N]-lysine, arginine and [13C6][15N2]-lysine, arginine labeled HEK293T cells at 20 uM after 1 hr by isotopic activity-based protein profiling-MudPIT assay	Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1. — J Med Chem
CHEMBL4201496	ADMET	Stability assessed as human ABHD6-mediated compound hydrolysis by HPLC analysis	( R)- N-(1-Methyl-2-hydroxyethyl)-13-( S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes. — J Med Chem
CHEMBL5723258	Functional	Affinity Biochemical interaction: (Gel-based competitive activity-based protein profiling with HT-01 probe and Neuro2A membrane proteomes) EUB0002617a ABHD6	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1IP	Abcam HeLa ABHD6 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.