DAGLA

Summary

DAGLA (diacylglycerol lipase alpha, HGNC:1165) is a protein-coding gene on chromosome 11q12.2, encoding Diacylglycerol lipase-alpha (Q9Y4D2). Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG).

This gene encodes a diacylglycerol lipase. The encoded enzyme is involved in the biosynthesis of the endocannabinoid 2-arachidonoyl-glycerol.

Source: NCBI Gene 747 — RefSeq curated summary.

At a glance

• Gene–disease (curated): benign paroxysmal tonic upgaze of childhood with ataxia (Strong, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 179 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006133

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1165
Approved symbol	DAGLA
Name	diacylglycerol lipase alpha
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0659, NSDDR, DAGLALPHA
Ensembl gene	ENSG00000134780
Ensembl biotype	protein_coding
OMIM	614015
Entrez	747

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000257215, ENST00000540717, ENST00000875660, ENST00000875661, ENST00000939713, ENST00000939714, ENST00000971001, ENST00000971002

RefSeq mRNA: 1 — MANE Select: NM_006133 NM_006133

CCDS: CCDS31578

Canonical transcript exons

ENST00000257215 — 20 exons

Exon	Start	End
ENSE00001196815	61720679	61720890
ENSE00001320370	61680391	61680504
ENSE00001321741	61720112	61720250
ENSE00002223801	61743532	61747001
ENSE00003481570	61737687	61737755
ENSE00003484442	61739465	61739661
ENSE00003527292	61725995	61726082
ENSE00003532059	61728931	61729008
ENSE00003533008	61731317	61731441
ENSE00003545479	61722859	61722960
ENSE00003552448	61734849	61735002
ENSE00003556118	61735739	61735816
ENSE00003560423	61740463	61740592
ENSE00003562124	61723434	61723572
ENSE00003589671	61735561	61735644
ENSE00003601945	61738135	61738207
ENSE00003624282	61728153	61728287
ENSE00003665004	61737182	61737324
ENSE00003665664	61736270	61736350
ENSE00003677508	61741162	61741349

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 85.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6119 / max 215.6569, expressed in 1264 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114593	3.5265	1261
114592	0.0854	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	85.75	gold quality
prefrontal cortex	UBERON:0000451	84.72	gold quality
Brodmann (1909) area 10	UBERON:0013541	83.22	gold quality
frontal cortex	UBERON:0001870	82.61	gold quality
neocortex	UBERON:0001950	82.00	gold quality
cingulate cortex	UBERON:0003027	81.58	gold quality
anterior cingulate cortex	UBERON:0009835	81.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.34	gold quality
cortical plate	UBERON:0005343	80.12	gold quality
cerebral cortex	UBERON:0000956	79.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.45	gold quality
telencephalon	UBERON:0001893	77.44	gold quality
lower esophagus mucosa	UBERON:0035834	76.78	gold quality
cerebellar hemisphere	UBERON:0002245	76.63	gold quality
cerebellar cortex	UBERON:0002129	76.60	gold quality
amygdala	UBERON:0001876	76.25	gold quality
primary visual cortex	UBERON:0002436	76.23	gold quality
forebrain	UBERON:0001890	76.08	gold quality
ventricular zone	UBERON:0003053	76.00	gold quality
cerebellum	UBERON:0002037	75.98	gold quality
Ammon’s horn	UBERON:0001954	75.95	gold quality
ganglionic eminence	UBERON:0004023	75.91	gold quality
superior frontal gyrus	UBERON:0002661	75.66	gold quality
brain	UBERON:0000955	75.37	gold quality
putamen	UBERON:0001874	75.04	gold quality
central nervous system	UBERON:0001017	74.98	gold quality
caudate nucleus	UBERON:0001873	74.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	74.77	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.67	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

202 targeting DAGLA, 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-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4267	99.96	66.53	2368

Literature-anchored findings (GeneRIF, showing 8)

• This gene was functionally characterized as a diacylglycerol-lipase (DAGL), specifically referred to as DAGL alpha. This enzyme may play a role in the biosynthesis of the endocannbinoid 2-arachidonoylglycerol (2-AG). (PMID:14610053)
• DAGLalpha mRNA expression is lowest in early life and adulthood, peaking between school age and young adulthood. (PMID:22827915)
• PLC-beta1 and DAGL-alpha are detected in discrete brain regions, with a marked predominance of pyramidal morphologies of positive cortical cells.[review] (PMID:24076015)
• In subcutaneous adipose tissue, DAGL-a mRNA was upregulated and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mRNAs were down-regulated in obese subjects, but the diets had no influence. (PMID:24616451)
• phenotypes associated with rare CNR1 variants are reminiscent of those implicated in the theory of clinical endocannabinoid deficiency syndrome. The severe phenotypes associated with rare DAGLA variants underscore the critical role of rapid 2-AG synthesis and the endocannabinoid system in regulating neurological function and development (PMID:29145497)
• Our findings indicated the involvement of DAGLA in alcoholism, possibly by its genetic dysfunction and also by the influence of stress (PMID:29477030)
• Overexpression of DAGLA in human oral squamous cell carcinomas cells controlled cell proliferation through cell-cycle progression. (PMID:29614312)
• Diacylglycerol lipase alpha promotes hepatocellular carcinoma progression and induces lenvatinib resistance by enhancing YAP activity. (PMID:37414748)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dagla	ENSDARG00000062956
mus_musculus	Dagla	ENSMUSG00000035735
rattus_norvegicus	Dagla	ENSRNOG00000027264
caenorhabditis_elegans		WBGENE00018364

Paralogs (3): GOLT1B (ENSG00000111711), DAGLB (ENSG00000164535), GOLT1A (ENSG00000174567)

Protein

Protein identifiers

Diacylglycerol lipase-alpha — Q9Y4D2 (reviewed: Q9Y4D2)

Alternative names: Neural stem cell-derived dendrite regulator, Sn1-specific diacylglycerol lipase alpha

All UniProt accessions (2): Q9Y4D2, F5GY58

UniProt curated annotations — full annotation on UniProt →

Function. Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG). Preferentially hydrolyzes sn-1 fatty acids from diacylglycerols (DAG) that contain arachidonic acid (AA) esterified at the sn-2 position to biosynthesize 2-AG. Has negligible activity against other lipids including monoacylglycerols and phospholipids. Plays a key role in regulating 2-AG signaling in the central nervous system (CNS). Regulates 2-AG involved in retrograde suppression at central synapses. Supports axonal growth during development and adult neurogenesis. Plays a role for eCB signaling in the physiological regulation of anxiety and depressive behaviors. Also regulates neuroinflammatory responses in the brain, in particular, LPS-induced microglial activation.

Subunit / interactions. Interacts (via C-terminal) with CAMK2A; leading to the phosphorylation and inhibition of DAGLA enzymatic activity. Interacts (via PPXXF motif) with HOMER1 and HOMER2; this interaction is required for DAGLA membrane localization.

Subcellular location. Cell membrane. Postsynaptic density membrane. Early endosome membrane. Cell projection. Dendritic spine membrane.

Tissue specificity. Highly expressed in brain and pancreas.

Post-translational modifications. Phosphorylated at Ser-782 and Ser-808 by CAMK2A; phosphorylation by CAMK2A inhibits diacylglycerol lipase activity.

Disease relevance. Spinocerebellar ataxia 20 (SCA20) [MIM:608687] Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA20 is an autosomal dominant, adult-onset form characterized by dysarthria due to spasmodic dysphonia followed by slowly progressive ataxia. The disease may be caused by variants affecting the gene represented in this entry. A copy number variation consisting of a 260-kb duplication at chromosome 11q12.2-12.3 is responsible for SCA20. The critical gene within the duplicated segment may be DAGLA. Neuroocular syndrome 2, paroxysmal type (NOC2) [MIM:168885] A form of neuroocular syndrome, a group of disorders characterized by developmental delay, impaired intellectual development and ocular anomalies as primary findings. NOC2 is an autosomal dominant form characterized by eye deviation or nystagmus with abnormal head posturing apparent from birth or early infancy. Affected individuals also have hypotonia, mild developmental delay, dysarthria, and gait ataxia. Most patients have mildly impaired intellectual development. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by 1,2,3-triazole urea covalent inhibitors KT172, DH376 and DO34. Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited by RHC80267. Diacylglycerol lipase activity is inhibited by the phosphorylation of Ser-782 and Ser-808 by CAMK2A.

Similarity. Belongs to the AB hydrolase superfamily. Lipase family.

RefSeq proteins (1): NP_006124* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002921	Fungal_lipase-type	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR052214	DAG_Lipase-Related	Family

Pfam: PF01764

Enzyme classification (BRENDA):

• EC 3.1.1.116 — sn-1-specific diacylglycerol lipase (BRENDA: 3 organisms, 23 substrates, 59 inhibitors, 1 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SN-1-STEAROYL-2-ARACHIDONOYL-GLYCEROL	0.1588	1

Catalyzed reactions (Rhea), 7 shown:

• a 1,2-diacyl-sn-glycerol + H2O = a 2-acylglycerol + a fatty acid + H(+) (RHEA:33275)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + octadecanoate + H(+) (RHEA:38507)
• 1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = 2-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38511)
• 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38515)
• 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol + H2O = 2-octadecanoylglycerol + (9Z)-octadecenoate + H(+) (RHEA:38519)
• 1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycerol + H2O = 2-(9Z,12Z-octadecadienoyl)-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38523)
• 1-(9Z-octadecenoyl)-2-O-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn-glycerol + H2O = 2-O-(5Z,8Z,11Z,14Z)-eicosatetraenylglycerol + (9Z)-octadecenoate + H(+) (RHEA:38527)

UniProt features (38 total): modified residue 12, sequence variant 7, topological domain 5, transmembrane region 4, mutagenesis site 4, region of interest 2, active site 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4D2-F1	63.87	0.26

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 (2): 472 (charge relay system); 524 (charge relay system)

Post-translational modifications (12): 727, 729, 732, 743, 782, 784, 806, 808, 833, 847, 952, 1023

Glycosylation sites (1): 133

Mutagenesis-validated functional residues (4):

Position	Phenotype
782	slightly reduces phosphorylation by camk2a. abolishes phosphorylation by camk2a; when associated with a-808.
782	phosphomimetic mutation; decreased the vmax of 2-ag production without affecting the km; when associated with e-808.
808	reduces phosphorylation by camk2a. abolishes phosphorylation by camk2a; when associated with a-782.
808	phosphomimetic mutation; decreased the vmax of 2-ag production without affecting the km; when associated with e-782.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-426048	Arachidonate production from DAG

MSigDB gene sets: 188 (showing top): GOBP_RESPONSE_TO_ETHANOL, GOBP_INFLAMMATORY_RESPONSE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_NEUROGENESIS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (11): monoacylglycerol biosynthetic process (GO:0006640), neuroblast proliferation (GO:0007405), arachidonate metabolic process (GO:0019369), diacylglycerol catabolic process (GO:0046340), retrograde trans-synaptic signaling by endocannabinoid (GO:0098921), regulation of neuroinflammatory response (GO:0150077), cannabinoid biosynthetic process (GO:1901696), lipid metabolic process (GO:0006629), acylglycerol metabolic process (GO:0006639), lipid catabolic process (GO:0016042), neurogenesis (GO:0022008)

GO Molecular Function (5): lipoprotein lipase activity (GO:0004465), metal ion binding (GO:0046872), monoacylglycerol lipase activity (GO:0047372), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): cytoplasm (GO:0005737), plasma membrane (GO:0005886), early endosome membrane (GO:0031901), dendrite membrane (GO:0032590), dendritic spine membrane (GO:0032591), varicosity (GO:0043196), postsynaptic membrane (GO:0045211), postsynaptic density membrane (GO:0098839), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Effects of PIP2 hydrolysis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
neuron projection membrane	2
synaptic membrane	2
monoacylglycerol metabolic process	1
acylglycerol biosynthetic process	1
generation of neurons	1
neural precursor cell proliferation	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
diacylglycerol metabolic process	1
acylglycerol catabolic process	1
retrograde trans-synaptic signaling by lipid	1
trans-synaptic signaling by endocannabinoid	1
regulation of inflammatory response	1
neuroinflammatory response	1
biosynthetic process	1
primary metabolic process	1
neutral lipid metabolic process	1
glycerolipid metabolic process	1
lipid metabolic process	1
catabolic process	1
nervous system development	1
cell differentiation	1
triacylglycerol lipase activity	1
cation binding	1
lipase activity	1
carboxylic ester hydrolase activity	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
early endosome	1
endosome membrane	1
dendrite	1
dendrite membrane	1
dendritic spine	1
main axon	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAGLA	FAAH	O00519	895
DAGLA	NAPEPLD	Q6IQ20	895
DAGLA	MGLL	Q99685	885
DAGLA	ABHD6	Q9BV23	827
DAGLA	CNR1	P21554	818
DAGLA	GRM5	P41594	805
DAGLA	ABHD12	Q8N2K0	783
DAGLA	ABHD4	Q8TB40	714
DAGLA	GPR55	Q9Y2T6	700
DAGLA	NAAA	Q02083	637
DAGLA	FAAH2	Q6GMR7	636
DAGLA	GDE1	Q9NZC3	635
DAGLA	TRPV1	Q8NER1	625
DAGLA	HOMER1	Q86YM7	582
DAGLA	HOMER2	Q9NSB8	563

IntAct

39 interactions, top by confidence:

A	B	Type	Score
DAGLA	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
VMA21	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
STOM	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
MAL	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
MS4A13	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
LHFPL5	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
MALL	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM7	DAGLA	psi-mi:“MI:0915”(physical association)	0.000
VMA21	DAGLA	psi-mi:“MI:0915”(physical association)	0.000
TMEM218	DAGLA	psi-mi:“MI:0915”(physical association)	0.000
TUSC5	DAGLA	psi-mi:“MI:0915”(physical association)	0.000
MALL	DAGLA	psi-mi:“MI:0915”(physical association)	0.000
UPK1B	DAGLA	psi-mi:“MI:0915”(physical association)	0.000
MS4A13	DAGLA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): DAGLA (Affinity Capture-RNA), DAGLA (Affinity Capture-RNA), DAGLA (Affinity Capture-MS), DAGLA (Affinity Capture-MS), DAGLA (Affinity Capture-MS), DAGLA (Affinity Capture-RNA), DAGLA (Affinity Capture-RNA), DAGLA (Two-hybrid), MALL (Two-hybrid), STOM (Two-hybrid), TMEM218 (Two-hybrid), CMTM7 (Two-hybrid), VMA21 (Two-hybrid), MAL (Two-hybrid), TUSC5 (Two-hybrid)

ESM2 similar proteins: A0A072VIM5, A0A0K0PU92, A0JM23, A2CIR7, F4IG73, F4JD14, G3LSH3, G8GTN7, O00750, O42132, O75460, O80560, P03372, P0CI65, P50241, P50242, P57717, P57753, Q0JJ01, Q29040, Q2HW56, Q2QXZ2, Q2RAQ5, Q53AD2, Q5D0W8, Q5M9H0, Q5YLM1, Q5ZLG9, Q6AZT7, Q6KAE5, Q6NLQ8, Q6PJI9, Q6WQJ1, Q7EZ44, Q7T0L6, Q7TNH6, Q7XAP4, Q7Z494, Q8C0M0, Q8CFE5

Diamond homologs: A2QSY5, B8NIB8, O42807, O42815, P0C1S9, Q0CBM7, Q2UNW5, Q5YLM1, Q6WQJ1, Q8NCG7, Q91WC9, Q9P979, Q9Y4D2, P61869, P61870

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
DAGLA	“down-regulates quantity”	1,2-diacyl-sn-glycerol	“chemical modification”
DAGLA	“up-regulates quantity”	2-arachidonoylglycerol	“chemical modification”
CAMK2A	“down-regulates activity”	DAGLA	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	111
Likely benign	31
Benign	10

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
2426363	NC_000011.9:g.(?61197619)(61552680_?)del	Pathogenic
3075711	NM_006133.3(DAGLA):c.2484del (p.Glu829fs)	Pathogenic
3233425	NM_006133.3(DAGLA):c.2370C>G (p.Tyr790Ter)	Pathogenic
3233426	NM_006133.3(DAGLA):c.2485G>T (p.Glu829Ter)	Pathogenic
3233428	NM_006133.3(DAGLA):c.2440G>T (p.Glu814Ter)	Pathogenic
3391177	NM_006133.3(DAGLA):c.2401del (p.Arg801fs)	Pathogenic
2662807	NM_006133.3(DAGLA):c.2551C>T (p.Gln851Ter)	Likely pathogenic
2663893	NM_006133.3(DAGLA):c.2437_2446del (p.Leu813fs)	Likely pathogenic
4616926	NM_006133.3(DAGLA):c.2389_2410del (p.Ser797fs)	Likely pathogenic

SpliceAI

3577 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61720251:G:A	donor_loss	1.0000
11:61720673:TGACA:T	acceptor_loss	1.0000
11:61720674:GACAG:G	acceptor_loss	1.0000
11:61720676:CAGG:C	acceptor_loss	1.0000
11:61720677:AGGTT:A	acceptor_loss	1.0000
11:61720678:GGTTT:G	acceptor_gain	1.0000
11:61720696:T:TA	acceptor_gain	1.0000
11:61720865:GCA:G	donor_gain	1.0000
11:61720868:G:GG	donor_gain	1.0000
11:61720888:TGGG:T	donor_loss	1.0000
11:61720889:GG:G	donor_gain	1.0000
11:61720890:GG:G	donor_gain	1.0000
11:61720891:G:GG	donor_gain	1.0000
11:61720891:GTA:G	donor_loss	1.0000
11:61720892:T:G	donor_loss	1.0000
11:61722854:TGCAG:T	acceptor_loss	1.0000
11:61722855:GCAGC:G	acceptor_loss	1.0000
11:61722856:CA:C	acceptor_loss	1.0000
11:61722857:A:AG	acceptor_gain	1.0000
11:61722858:G:GT	acceptor_gain	1.0000
11:61722858:GC:G	acceptor_gain	1.0000
11:61722858:GCC:G	acceptor_gain	1.0000
11:61722858:GCCA:G	acceptor_gain	1.0000
11:61722858:GCCAT:G	acceptor_gain	1.0000
11:61722960:GGTA:G	donor_loss	1.0000
11:61722961:G:GG	donor_gain	1.0000
11:61722961:GT:G	donor_loss	1.0000
11:61723429:CGCA:C	acceptor_loss	1.0000
11:61723431:CA:C	acceptor_loss	1.0000
11:61723432:AG:A	acceptor_gain	1.0000

AlphaMissense

6739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61720162:G:A	G3R	1.000
11:61720162:G:C	G3R	1.000
11:61720162:G:T	G3W	1.000
11:61720186:T:A	W11R	1.000
11:61720186:T:C	W11R	1.000
11:61720195:G:C	G14R	1.000
11:61720201:G:C	D16H	1.000
11:61720201:G:T	D16Y	1.000
11:61720202:A:C	D16A	1.000
11:61720202:A:G	D16G	1.000
11:61720202:A:T	D16V	1.000
11:61720203:T:A	D16E	1.000
11:61720203:T:G	D16E	1.000
11:61720204:G:C	D17H	1.000
11:61720205:A:G	D17G	1.000
11:61720205:A:T	D17V	1.000
11:61720208:T:C	L18P	1.000
11:61720764:G:C	G61R	1.000
11:61720780:T:C	L66P	1.000
11:61720785:A:C	S68R	1.000
11:61720787:C:A	S68R	1.000
11:61720787:C:G	S68R	1.000
11:61720821:A:C	S80R	1.000
11:61720823:C:A	S80R	1.000
11:61720823:C:G	S80R	1.000
11:61720830:G:A	G83R	1.000
11:61720830:G:C	G83R	1.000
11:61720831:G:A	G83E	1.000
11:61720854:C:A	R91S	1.000
11:61722894:G:C	G115R	1.000

dbSNP variants (sampled 300 via entrez): RS1000064551 (11:61718825 G>A), RS1000095021 (11:61719087 T>C), RS1000164248 (11:61732346 C>G), RS1000202489 (11:61746776 G>A), RS1000226738 (11:61702153 G>A), RS1000275147 (11:61696044 C>T), RS1000317512 (11:61696398 G>A,T), RS1000318943 (11:61713965 G>A), RS1000324301 (11:61696212 G>A,T), RS1000397692 (11:61731092 C>T), RS1000497688 (11:61730781 C>A,G,T), RS1000517261 (11:61689166 C>T), RS1000536699 (11:61736719 T>G), RS1000537630 (11:61683401 G>A), RS1000573933 (11:61701942 A>T)

Disease associations

OMIM: gene MIM:614015 | disease phenotypes: MIM:168000, MIM:164400, MIM:168885, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
benign paroxysmal tonic upgaze of childhood with ataxia	Strong	Autosomal dominant

Mondo (5): hereditary pheochromocytoma-paraganglioma (MONDO:0017366), autosomal dominant cerebellar ataxia (MONDO:0020380), benign paroxysmal tonic upgaze of childhood with ataxia (MONDO:0008206), autism (MONDO:0005260), attention deficit-hyperactivity disorder (MONDO:0007743)

Orphanet (3): Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Autosomal dominant cerebellar ataxia (Orphanet:99), Benign paroxysmal tonic upgaze of childhood with ataxia (Orphanet:1179)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001179_19	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	3.000000e-09
GCST001180_4	Plasma omega-3 polyunsaturated fatty acid levels (alphalinolenic acid)	1.000000e-08
GCST001535_8	Immune reponse to smallpox (secreted IL-2)	2.000000e-07
GCST002444_5	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	5.000000e-168
GCST002446_1	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	4.000000e-274
GCST002446_7	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	3.000000e-21
GCST002448_6	Plasma omega-6 polyunsaturated fatty acid levels (adrenic acid)	4.000000e-140
GCST002449_6	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	0.000000e+00
GCST002449_8	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	7.000000e-147
GCST002450_8	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	2.000000e-72
GCST002712_4	Red blood cell fatty acid levels	3.000000e-305
GCST004139_22	Bipolar disorder	6.000000e-09
GCST008103_71	Bipolar disorder	8.000000e-07
GCST010002_239	Refractive error	2.000000e-24
GCST011685_3	Fasting plasma glucose	7.000000e-07

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006809	docosapentaenoic acid measurement
EFO:0007759	alpha-linolenic acid measurement
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0006811	linolenic acid measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
C566817	Paroxysmal Tonic Upgaze, Benign Childhood, With Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5545 (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: 52,952 (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
CHEMBL2387742	CANNABIDIVARIN	2	4,963
CHEMBL498672	CANNABIDIOLIC ACID	2	9,803

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
DO34	Inhibition	8.2	pIC50
DH376	Inhibition	8.2	pIC50
LEI105	Inhibition	7.89	pIC50
orlistat	Inhibition	7.2	pIC50
KT-109	Inhibition	5.64	pIC50
RHC80267	Inhibition	4.19	pIC50

ChEMBL bioactivities

207 potent at pChembl≥5 of 223 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.60	IC50	0.2512	nM	CHEMBL4476210
9.40	IC50	0.3981	nM	CHEMBL4476210
9.30	IC50	0.5012	nM	CHEMBL4581240
9.22	IC50	0.6	nM	CHEMBL3764017
9.20	IC50	0.631	nM	CHEMBL3897587
9.10	IC50	0.7943	nM	CHEMBL3954476
9.10	IC50	0.7943	nM	CHEMBL3906477
9.10	IC50	0.7943	nM	CHEMBL3913807
9.10	IC50	0.7943	nM	CHEMBL4279328
9.05	IC50	0.9	nM	CHEMBL3765578
9.00	IC50	1	nM	CHEMBL3970032
8.90	IC50	1.259	nM	CHEMBL3895863
8.62	IC50	2.4	nM	CHEMBL3764876
8.60	IC50	2.512	nM	CHEMBL3964338
8.52	IC50	3	nM	CHEMBL3763826
8.52	IC50	3	nM	CHEMBL3765716
8.52	IC50	3	nM	CHEMBL3763853
8.50	IC50	3.162	nM	CHEMBL3941507
8.50	IC50	3.162	nM	CHEMBL4447844
8.44	IC50	3.631	nM	CHEMBL182199
8.40	IC50	4	nM	CHEMBL3763831
8.40	IC50	3.981	nM	CHEMBL4476210
8.30	IC50	5.012	nM	CHEMBL3903742
8.30	IC50	5.012	nM	CHEMBL3921538
8.30	IC50	5.012	nM	CHEMBL3916842
8.22	IC50	6	nM	CHEMBL3765421
8.22	IC50	6	nM	CHEMBL3764093
8.20	IC50	6.31	nM	CHEMBL2144065
8.20	IC50	6.31	nM	CHEMBL3986579
8.10	IC50	8	nM	CHEMBL3765022
8.10	IC50	8	nM	CHEMBL3763430
8.10	IC50	7.943	nM	CHEMBL3922787
8.10	IC50	7.943	nM	CHEMBL3897762
8.00	IC50	10	nM	ORLISTAT
7.96	IC50	11	nM	CHEMBL3765158
7.90	IC50	12.59	nM	CHEMBL3931744
7.90	IC50	12.59	nM	CHEMBL3925845
7.90	IC50	12.59	nM	CHEMBL4447844
7.85	IC50	14	nM	CHEMBL3763853
7.84	IC50	14.3	nM	CHEMBL3764876
7.80	IC50	16	nM	CHEMBL3765824
7.80	IC50	15.85	nM	CHEMBL4287766
7.80	IC50	15.85	nM	CHEMBL4281906
7.80	IC50	15.85	nM	CHEMBL4294845
7.80	IC50	16	nM	CHEMBL521157
7.77	IC50	17	nM	CHEMBL3764778
7.77	IC50	17	nM	CHEMBL3764377
7.75	IC50	18	nM	CHEMBL3319620
7.75	IC50	18	nM	CHEMBL3765573
7.72	IC50	19	nM	CHEMBL3765497

PubChem BioAssay actives

186 with measured affinity, of 416 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
1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate	1627065: Inhibition of human C-terminal HA-tagged DAGLalpha expressed in HEK293F cell membrane fractions using PNP butyrate as substrate by colorimetric surrogate substrate assay	ic50	0.0003	uM
tert-butyl 3-benzyl-4-[4-[4-(trifluoromethoxy)phenyl]triazole-1-carbonyl]piperazine-1-carboxylate	1627072: Inhibition human DAGLalpha expressed in HEK293T cell membrane fractions using DAG as substrate preincubated for 30 mins followed by ABP HT01 probe addition measured after 30 mins in presence of probe by gel-based ABPP competition assay	ic50	0.0005	uM
[(2R,5R)-2-benzyl-5-(cyclopropylmethoxy)piperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0006	uM
2-[[1-[3-(3,5-dichlorophenyl)phenyl]cyclobutyl]-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0006	uM
[(2R,5R)-2-benzyl-5-methoxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0008	uM
[(2R)-2-benzylpiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0008	uM
[(6S)-6-benzyl-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415832: Inhibition of recombinant human DAGLalpha expressed in HEK293 cells using PNP-butyrate as substrate pretreated for 20 to 30 mins followed by substrate addition measured every 60 secs for 20 mins by colorimetric method	ic50	0.0008	uM
[(2R)-2-benzylpiperidin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0008	uM
2-[[1-[3-(3,5-dichlorophenyl)phenyl]cyclopentyl]-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0009	uM
(2-benzylpiperidin-1-yl)-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0010	uM
Orlistat	1279167: Inhibition of human recombinant DAGLalpha expressed in African green monkey COS cells using sn-1-stearoyl-2-[14C]-arachidonoyl-glycerol as substrate incubated for 15 mins by beta counting analysis	ic50	0.0010	uM
[(2R,5R)-2-benzyl-5-prop-2-ynoxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0013	uM
2-[3-(2,3-dichlorophenyl)-N-[4-(difluoromethoxy)phenyl]sulfonylanilino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0024	uM
(2-benzylpiperidin-1-yl)-[4-[hydroxy(diphenyl)methyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0025	uM
2-[[3-(2,3-dichlorophenyl)phenyl]methyl-[4-(difluoromethoxy)phenyl]sulfonylamino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0030	uM
2-[[3-(3,5-dichlorophenyl)phenyl]methyl-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0030	uM
2-[[4-(3,5-dichlorophenyl)phenyl]methyl-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0030	uM
1-[6-(4-methylphenyl)-[1,3]oxazolo[4,5-b]pyridin-2-yl]-6-phenylhexan-1-one	1627075: Inhibition of human DAGLalpha expressed in HEK293T cell membrane fractions using PNP butyrate as substrate preincubated for 20 mins followed by substrate addition by colorimetric surrogate substrate assay	ic50	0.0032	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-[(3-methoxyphenyl)methyl]piperidin-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0032	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-9-phenylnonan-1-one	1270928: Inhibition of full-length human DAGLalpha expressed in HEK293T cell membranes using para-nitrophenylbutyrate by colorimetric assay	ic50	0.0036	uM
2-[(4-chlorophenyl)sulfonyl-[1-[3-(3,5-dichlorophenyl)phenyl]cyclobutyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0040	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-[(4-methoxyphenyl)methyl]piperidin-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0050	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-[(4-fluorophenoxy)methyl]piperidin-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0050	uM
[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]-[2-(phenoxymethyl)piperidin-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0050	uM
2-[[1-[4-(2,4-dichlorophenyl)phenyl]cyclobutyl]-[4-(difluoromethoxy)phenyl]sulfonylamino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0060	uM
2-[[1-[3-(2,4-dichlorophenyl)phenyl]cyclobutyl]-(3,4-dichlorophenyl)sulfonylamino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0060	uM
[2-[(4-fluorophenoxy)methyl]piperidin-1-yl]-[4-[hydroxy(diphenyl)methyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0063	uM
(2-benzylpiperidin-1-yl)-[4-(4-phenylphenyl)triazol-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0063	uM
[4-[hydroxy(diphenyl)methyl]triazol-2-yl]-[2-(phenoxymethyl)piperidin-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0079	uM
[(2R,5S)-2-benzyl-5-methoxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0079	uM
2-[[3-[4-(3,5-dichlorophenyl)phenyl]oxolan-3-yl]-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0080	uM
2-[[4-(difluoromethoxy)phenyl]sulfonyl-[1-[4-[2-(trifluoromethoxy)phenyl]phenyl]cyclobutyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0080	uM
2-[[1-[3-(3,5-dichlorophenyl)phenyl]cyclobutyl]-[4-(difluoromethoxy)phenyl]sulfonylamino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0110	uM
[(3R,6S)-6-benzyl-3-hydroxy-3,6-dihydro-2H-pyridin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0126	uM
(2-benzylpiperidin-1-yl)-[4-[bis(4-fluorophenyl)-methoxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0126	uM
[4-(4-nitrophenyl)triazol-1-yl]-[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]methanone	1415832: Inhibition of recombinant human DAGLalpha expressed in HEK293 cells using PNP-butyrate as substrate pretreated for 20 to 30 mins followed by substrate addition measured every 60 secs for 20 mins by colorimetric method	ic50	0.0158	uM
[(3R,6S)-6-benzyl-3-hydroxy-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415832: Inhibition of recombinant human DAGLalpha expressed in HEK293 cells using PNP-butyrate as substrate pretreated for 20 to 30 mins followed by substrate addition measured every 60 secs for 20 mins by colorimetric method	ic50	0.0158	uM
[4-(4-bromophenyl)triazol-1-yl]-[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]methanone	1415832: Inhibition of recombinant human DAGLalpha expressed in HEK293 cells using PNP-butyrate as substrate pretreated for 20 to 30 mins followed by substrate addition measured every 60 secs for 20 mins by colorimetric method	ic50	0.0158	uM
2-[[3-(3,5-dichlorophenyl)phenyl]methyl-[4-(difluoromethoxy)phenyl]sulfonylamino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0160	uM
[(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-2-formamido-3-methylpentanoate	389886: Inhibition of human recombinant DAGL-alpha-mediated sn-1-[14C]oleoyl-2-arachidonoyl-glycerol hydrolysis to 2-AG overexpressed in african green monkey COS7 cell membrane by scintillation counting	ic50	0.0160	uM
2-[[4-(difluoromethoxy)phenyl]sulfonyl-[[3-[2-(trifluoromethoxy)phenyl]phenyl]methyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0170	uM
2-[[4-(difluoromethoxy)phenyl]sulfonyl-[[4-[2-(trifluoromethoxy)phenyl]phenyl]methyl]amino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0170	uM
2-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl-[(4-phenoxyphenyl)methyl]amino]acetic acid	1182010: Inhibition of human DAGLalpha expressed in HEK293T cell membranes	ic50	0.0180	uM
2-[[(1S)-1-[4-(2,4-dichlorophenyl)phenyl]ethyl]-[4-(difluoromethoxy)phenyl]sulfonylamino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0180	uM
2-[[(1R)-1-[4-(2,4-dichlorophenyl)phenyl]ethyl]-[4-(difluoromethoxy)phenyl]sulfonylamino]acetic acid	1279166: Inhibition of full length human C-terminal HA-tagged DAGLalpha expressed in HEK293 cell membrane using DAG as substrate incubated for 20 mins by LC-MS analysis	ic50	0.0190	uM
[(3S,6S)-6-benzyl-3-hydroxy-3,6-dihydro-2H-pyridin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0199	uM
[(2R,5R)-2-benzyl-5-hydroxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0199	uM
(2-ethylpiperidin-1-yl)-[4-(4-phenylphenyl)triazol-1-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0199	uM
[(2R,5S)-2-benzyl-5-(cyclopropylmethoxy)piperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone	1339017: Inhibition of full length recombinant human DAGLalpha expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay	ic50	0.0199	uM
[(6R)-6-(phenylmethoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-[4-(4-phenylphenyl)triazol-1-yl]methanone	1415832: Inhibition of recombinant human DAGLalpha expressed in HEK293 cells using PNP-butyrate as substrate pretreated for 20 to 30 mins followed by substrate addition measured every 60 secs for 20 mins by colorimetric method	ic50	0.0251	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
kojic acid	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
tamibarotene	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
1-stearoyl-2-arachidonoylglycerol	increases metabolic processing	1
methyl arachidonylfluorophosphonate	decreases activity	1
arachidonyl-2-chloroethylamide	decreases reaction, increases expression, affects reaction	1
GSK5182	decreases reaction, increases expression	1
Sunitinib	decreases expression	1
Orlistat	decreases activity	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	affects expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

48 unique, capped per target: 48 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1227523	Binding	Inhibition of recombinant DAGLalpha expressed in HEK293 cells assessed as hydrolysis of 1-stearoyl-2-arachidonoyl-glycerol to 2-AG at 25 uM after 30 mins by LC-MS method	Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. — Nat Chem Biol

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation