DAGLB

Summary

DAGLB (diacylglycerol lipase beta, HGNC:28923) is a protein-coding gene on chromosome 7p22.1, encoding Diacylglycerol lipase-beta (Q8NCG7). Lipase that catalyzes the hydrolysis of arachidonic acid (AA)-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) which can be further cleaved by downstream enzymes to release arachidonic acid (AA) for cyclooxygenase (COX)-me….

Enables lipase activity. Involved in arachidonate metabolic process. Located in nucleoplasm and plasma membrane.

Source: NCBI Gene 221955 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 215 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_139179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28923
Approved symbol	DAGLB
Name	diacylglycerol lipase beta
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	KCCR13L, DAGLBETA
Ensembl gene	ENSG00000164535
Ensembl biotype	protein_coding
OMIM	614016
Entrez	221955

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 21 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000297056, ENST00000425398, ENST00000432248, ENST00000436575, ENST00000454738, ENST00000462934, ENST00000479922, ENST00000482149, ENST00000483716, ENST00000497308, ENST00000878456, ENST00000878457, ENST00000878458, ENST00000878459, ENST00000878460, ENST00000878461, ENST00000878462, ENST00000878463, ENST00000878464, ENST00000878465, ENST00000930342, ENST00000930343, ENST00000930344, ENST00000930345, ENST00000930346, ENST00000947925, ENST00000947926

RefSeq mRNA: 2 — MANE Select: NM_139179 NM_001142936, NM_139179

CCDS: CCDS47536, CCDS5350

Canonical transcript exons

ENST00000297056 — 15 exons

Exon	Start	End
ENSE00001085265	6430480	6430607
ENSE00001085278	6434762	6435020
ENSE00001642968	6447748	6447954
ENSE00001905547	6409129	6410035
ENSE00003458915	6421727	6421804
ENSE00003506570	6445953	6446104
ENSE00003514205	6436362	6436533
ENSE00003547833	6412811	6412883
ENSE00003554987	6432837	6432959
ENSE00003563626	6412966	6413034
ENSE00003638468	6416627	6416754
ENSE00003654658	6410130	6410380
ENSE00003661407	6425988	6426114
ENSE00003666004	6424752	6424835
ENSE00003666658	6416841	6416921

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 91.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2172 / max 237.6142, expressed in 1806 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82654	267.7552	1827
82645	16.4865	1804
82644	0.7307	324

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	91.14	gold quality
pancreatic ductal cell	CL:0002079	90.66	silver quality
monocyte	CL:0000576	89.79	gold quality
leukocyte	CL:0000738	89.54	gold quality
right adrenal gland cortex	UBERON:0035827	89.27	gold quality
right adrenal gland	UBERON:0001233	89.16	gold quality
left adrenal gland	UBERON:0001234	89.14	gold quality
left adrenal gland cortex	UBERON:0035825	88.79	gold quality
adrenal cortex	UBERON:0001235	87.81	gold quality
skin of leg	UBERON:0001511	87.72	gold quality
adrenal gland	UBERON:0002369	87.47	gold quality
lower esophagus mucosa	UBERON:0035834	86.62	gold quality
skin of abdomen	UBERON:0001416	86.41	gold quality
blood	UBERON:0000178	86.32	gold quality
right frontal lobe	UBERON:0002810	86.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.02	gold quality
upper lobe of left lung	UBERON:0008952	85.80	gold quality
stromal cell of endometrium	CL:0002255	85.58	gold quality
zone of skin	UBERON:0000014	85.31	gold quality
upper arm skin	UBERON:0004263	85.22	gold quality
gastrocnemius	UBERON:0001388	85.11	gold quality
decidua	UBERON:0002450	85.04	gold quality
adrenal tissue	UBERON:0018303	85.02	gold quality
mucosa of stomach	UBERON:0001199	84.86	gold quality
upper lobe of lung	UBERON:0008948	84.86	gold quality
muscle of leg	UBERON:0001383	84.78	gold quality
right lung	UBERON:0002167	84.68	gold quality
prefrontal cortex	UBERON:0000451	84.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting DAGLB, 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-493-5P	99.96	72.47	2382
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127
HSA-MIR-571	95.38	66.54	671
HSA-MIR-6786-3P	93.73	60.70	52

Literature-anchored findings (GeneRIF, showing 3)

• This gene has been functionally characterized as a diacylglycerol-lipase (DAGL), referred to as DAGL beta. These enzymes may have a role in the biosynthesis of the endocannabinoid 2-arachidnoyl glycerol (2-AG). (PMID:14610053)
• The purified DAGLbeta catalytic domain assay described here provides the basis for a relatively clean and convenient assay with the potential to be adapted for high-throughput drug discovery efforts. (PMID:27115711)
• we identified a novel HDL-C-associated variant which explained nearly half of the expression variance of DAGLB. (PMID:29476167)

Cross-species orthologs

26 orthologs

Organism	Symbol	Gene ID
danio_rerio	daglb	ENSDARG00000089888
mus_musculus	Daglb	ENSMUSG00000039206
rattus_norvegicus	Daglb	ENSRNOG00000001079
caenorhabditis_elegans		WBGENE00007112
caenorhabditis_elegans		WBGENE00008042
caenorhabditis_elegans		WBGENE00008043
caenorhabditis_elegans		WBGENE00008044
caenorhabditis_elegans		WBGENE00009237
caenorhabditis_elegans		WBGENE00013035
caenorhabditis_elegans		WBGENE00013037
caenorhabditis_elegans		WBGENE00013044
caenorhabditis_elegans		WBGENE00013101
caenorhabditis_elegans		WBGENE00013949
caenorhabditis_elegans		WBGENE00013950
caenorhabditis_elegans		WBGENE00015775
caenorhabditis_elegans		WBGENE00017764
caenorhabditis_elegans		WBGENE00019029
caenorhabditis_elegans		WBGENE00019269
caenorhabditis_elegans		WBGENE00019368
caenorhabditis_elegans		WBGENE00020341
caenorhabditis_elegans		WBGENE00020393
caenorhabditis_elegans		WBGENE00020662
caenorhabditis_elegans		WBGENE00021601
caenorhabditis_elegans	Y110A7A.7	WBGENE00022457
caenorhabditis_elegans		WBGENE00044488
caenorhabditis_elegans		WBGENE00189950

Paralogs (3): GOLT1B (ENSG00000111711), DAGLA (ENSG00000134780), GOLT1A (ENSG00000174567)

Protein

Protein identifiers

Diacylglycerol lipase-beta — Q8NCG7 (reviewed: Q8NCG7)

Alternative names: KCCR13L, PUFA-specific triacylglycerol lipase, Sn1-specific diacylglycerol lipase beta

All UniProt accessions (4): C9JA85, E7ET49, Q8NCG7, F8WBN0

UniProt curated annotations — full annotation on UniProt →

Function. Lipase that catalyzes the hydrolysis of arachidonic acid (AA)-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) which can be further cleaved by downstream enzymes to release arachidonic acid (AA) for cyclooxygenase (COX)-mediated eicosanoid production. Preferentially hydrolyzes DAGs at the sn-1 position in a calcium-dependent manner and has negligible activity against other lipids including monoacylglycerols and phospholipids. Plays a key role in the regulation of 2-AG and AA pools utilized by COX1/2 to generate lipid mediators of macrophage and microglia inflammatory responses. Also functions as a polyunsaturated fatty acids-specific triacylglycerol lipase in macrophages. Plays an important role to support the metabolic and signaling demands of macrophages.

Subcellular location. Cell membrane.

Activity regulation. Inhibited by the 1,2,3-triazole urea covalent inhibitors KT109 and KT172. Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not by PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NCG7-1	1	yes
Q8NCG7-2	2
Q8NCG7-3	3
Q8NCG7-4	4

RefSeq proteins (2): NP_001136408, NP_631918* (*=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), 10 shown:

• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)
• 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)
• 1,2,3-tri-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = 1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:63432)
• 1,2,3-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + H2O = 1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + H(+) (RHEA:63436)

UniProt features (27 total): topological domain 5, modified residue 5, splice variant 4, transmembrane region 4, sequence conflict 3, active site 2, mutagenesis site 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCG7-F1	73.18	0.23

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): 443 (charge relay system); 495 (charge relay system)

Post-translational modifications (5): 570, 574, 579, 583, 584

Mutagenesis-validated functional residues (2):

Position	Phenotype
443	loss of activity.
495	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-426048	Arachidonate production from DAG

MSigDB gene sets: 197 (showing top): GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEUROGENESIS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, chr7p22, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (12): prostaglandin biosynthetic process (GO:0001516), monoacylglycerol biosynthetic process (GO:0006640), neuroblast proliferation (GO:0007405), positive regulation of triglyceride catabolic process (GO:0010898), arachidonate metabolic process (GO:0019369), neurogenesis (GO:0022008), diacylglycerol catabolic process (GO:0046340), regulation of inflammatory response (GO:0050727), cannabinoid biosynthetic process (GO:1901696), lipid metabolic process (GO:0006629), icosanoid metabolic process (GO:0006690), lipid catabolic process (GO:0016042)

GO Molecular Function (6): triacylglycerol lipase activity (GO:0004806), lipase activity (GO:0016298), metal ion binding (GO:0046872), monoacylglycerol lipase activity (GO:0047372), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleoplasm (GO:0005654), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), membrane (GO:0016020)

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
lipase activity	2
carboxylic ester hydrolase activity	2
cellular anatomical structure	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
monoacylglycerol metabolic process	1
acylglycerol biosynthetic process	1
generation of neurons	1
neural precursor cell proliferation	1
regulation of triglyceride catabolic process	1
triglyceride catabolic process	1
positive regulation of lipid catabolic process	1
positive regulation of triglyceride metabolic process	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
nervous system development	1
cell differentiation	1
diacylglycerol metabolic process	1
acylglycerol catabolic process	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
biosynthetic process	1
primary metabolic process	1
carboxylic acid metabolic process	1
lipid metabolic process	1
catabolic process	1
hydrolase activity, acting on ester bonds	1
cation binding	1
binding	1
catalytic activity	1
nuclear lumen	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAGLB	NAPEPLD	Q6IQ20	890
DAGLB	FAAH	O00519	848
DAGLB	MGLL	Q99685	830
DAGLB	ABHD6	Q9BV23	811
DAGLB	ABHD12	Q8N2K0	744
DAGLB	CNR1	P21554	705
DAGLB	ABHD4	Q8TB40	678
DAGLB	FAAH2	Q6GMR7	651
DAGLB	NAAA	Q02083	642
DAGLB	GDE1	Q9NZC3	634
DAGLB	GPR55	Q9Y2T6	621
DAGLB	CNRIP1	Q96F85	555
DAGLB	TRPV1	Q8NER1	530
DAGLB	CNR2	P34972	484
DAGLB	MTHFSD	Q2M296	438

IntAct

71 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
NOTCH2NLC	DAGLB	psi-mi:“MI:0915”(physical association)	0.560
DAGLB	CLP1	psi-mi:“MI:0915”(physical association)	0.560
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
TSPAN2	TSPAN3	psi-mi:“MI:0914”(association)	0.530
ENTPD7	PGK2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SPACA1	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
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TSPAN31	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS), DAGLB (Affinity Capture-MS)

ESM2 similar proteins: A2AWR3, F7B909, O94830, P0C1S9, P0CF65, P32870, Q008S8, Q08462, Q09427, Q09428, Q09429, Q0DWA9, Q0P564, Q0P5W1, Q0WMJ8, Q14BI7, Q2TBM9, Q3KTM2, Q3MHU3, Q3U213, Q3UUQ7, Q3UYK3, Q5SNQ7, Q5YLM1, Q5Z413, Q60963, Q61542, Q640S2, Q68EH9, Q68FJ9, Q6NTN5, Q6WQJ1, Q765A7, Q7T163, Q80Y98, Q8C7D2, Q8IUA7, Q8K449, Q8N3P4, Q8NCG7

Diamond homologs: A0A3G2S8R6, A0A6C0PI29, A0A8R9Z5V5, A2QSY5, A2WT96, B8NIB8, B9EYD3, I1RCD3, I1RPD9, O42807, O42815, O59952, P0C1S9, P0CT85, P0CT91, P19515, P61869, P61870, Q0CBM7, Q0JKT4, Q2UNW5, Q8NCG7, Q91WC9, Q948R1, Q9HE20, Q9P979, Q9XTR8, P61871, P61872, Q9C8J6, Q5YLM1, Q6WQJ1, Q9Y4D2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DAGLB	“down-regulates quantity”	1,2-diacyl-sn-glycerol	“chemical modification”
DAGLB	“up-regulates quantity”	“episterol ester”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class A/1 (Rhodopsin-like receptors)	7	11.3×	3e-04
GPCR ligand binding	7	9.8×	5e-04
GPCR downstream signalling	8	7.5×	5e-04
Signaling by GPCR	8	7.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	164
Likely benign	11
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3486 predictions. Top by Δscore:

Variant	Effect	Δscore
7:6410128:ACCG:A	donor_gain	1.0000
7:6410128:ACCGC:A	donor_gain	1.0000
7:6410129:CCG:C	donor_gain	1.0000
7:6410129:CCGC:C	donor_gain	1.0000
7:6410129:CCGCC:C	donor_gain	1.0000
7:6410148:T:TA	donor_gain	1.0000
7:6410376:TTGTA:T	acceptor_gain	1.0000
7:6410381:C:CC	acceptor_gain	1.0000
7:6412806:CTTA:C	donor_loss	1.0000
7:6412808:TACC:T	donor_loss	1.0000
7:6412809:A:AC	donor_gain	1.0000
7:6412809:ACCTT:A	donor_loss	1.0000
7:6412810:C:CC	donor_gain	1.0000
7:6412879:TGAGC:T	acceptor_gain	1.0000
7:6412880:GAGC:G	acceptor_gain	1.0000
7:6412881:AGCC:A	acceptor_loss	1.0000
7:6412882:GC:G	acceptor_gain	1.0000
7:6412883:CC:C	acceptor_gain	1.0000
7:6412883:CCTGT:C	acceptor_loss	1.0000
7:6412884:C:CC	acceptor_gain	1.0000
7:6412884:C:G	acceptor_loss	1.0000
7:6412885:T:C	acceptor_loss	1.0000
7:6412960:GCTTA:G	donor_loss	1.0000
7:6412961:CTTAC:C	donor_loss	1.0000
7:6412962:TTA:T	donor_loss	1.0000
7:6412963:TA:T	donor_loss	1.0000
7:6412964:A:AG	donor_loss	1.0000
7:6412965:C:CA	donor_loss	1.0000
7:6413030:CTTTG:C	acceptor_gain	1.0000
7:6413031:TTTG:T	acceptor_gain	1.0000

AlphaMissense

4390 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:6424771:C:A	R374M	0.998
7:6424780:A:T	V371D	0.998
7:6416726:C:A	S443I	0.997
7:6424786:A:T	V369D	0.997
7:6432939:G:C	S233R	0.997
7:6432939:G:T	S233R	0.997
7:6432941:T:G	S233R	0.997
7:6412979:C:G	D495H	0.996
7:6416725:G:C	S443R	0.996
7:6416725:G:T	S443R	0.996
7:6416727:T:G	S443R	0.996
7:6416884:A:G	L419P	0.996
7:6424771:C:G	R374T	0.996
7:6432937:T:G	D234A	0.996
7:6447812:A:G	W11R	0.996
7:6447812:A:T	W11R	0.996
7:6412811:C:A	K523N	0.995
7:6412811:C:G	K523N	0.995
7:6412877:A:C	S501R	0.995
7:6412877:A:T	S501R	0.995
7:6412879:T:G	S501R	0.995
7:6421732:G:C	H405D	0.995
7:6424768:C:A	G375V	0.995
7:6445960:G:C	S80R	0.995
7:6445960:G:T	S80R	0.995
7:6445962:T:G	S80R	0.995
7:6409939:G:C	H639Q	0.994
7:6409939:G:T	H639Q	0.994
7:6409941:G:C	H639D	0.994
7:6416884:A:T	L419H	0.994

dbSNP variants (sampled 300 via entrez): RS1000053523 (7:6424560 T>G), RS1000107901 (7:6441600 G>A,T), RS1000108332 (7:6425755 C>G), RS1000118450 (7:6425616 A>C), RS1000171059 (7:6422365 G>C), RS1000171240 (7:6414755 C>A,T), RS1000185104 (7:6444400 G>A,C), RS1000218781 (7:6449725 G>A), RS1000229358 (7:6444226 T>A,C), RS1000264724 (7:6430581 T>C), RS1000341101 (7:6447549 C>A,T), RS1000392720 (7:6418241 T>C), RS1000579241 (7:6422690 T>A), RS1000615789 (7:6443366 T>C), RS1000632519 (7:6418733 C>T)

Disease associations

OMIM: gene MIM:614016 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST002223_26	HDL cholesterol	6.000000e-12
GCST004131_9	Inflammatory bowel disease	4.000000e-08
GCST004133_37	Ulcerative colitis	2.000000e-06
GCST004232_53	HDL cholesterol levels	1.000000e-14
GCST004632_54	Lymphocyte percentage of white cells	2.000000e-13
GCST004633_66	Neutrophil percentage of white cells	7.000000e-25
GCST005194_226	Coronary artery disease	1.000000e-07
GCST005195_103	Coronary artery disease	2.000000e-08
GCST005951_155	Body mass index	1.000000e-08
GCST006611_53	HDL cholesterol	3.000000e-13
GCST007483_55	Waist-to-hip ratio adjusted for BMI (additive genetic model)	6.000000e-08
GCST007487_45	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-08
GCST007500_37	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-09
GCST007502_35	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-09
GCST008075_117	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-15
GCST008075_64	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-10
GCST008084_190	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-16
GCST008084_25	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	8.000000e-12
GCST008085_184	HDL cholesterol levels in current drinkers	1.000000e-06
GCST010219_9	Attention deficit hyperactivity disorder (inattention symptoms)	3.000000e-07
GCST010242_480	HDL cholesterol levels	3.000000e-33
GCST011328_4	Waist-hip ratio and HDL-C (pairwise)	7.000000e-14
GCST011348_10	High density lipoprotein cholesterol levels	7.000000e-10
GCST90002398_418	Neutrophil count	2.000000e-14
GCST90002404_278	Red cell distribution width	7.000000e-12
GCST90002404_279	Red cell distribution width	7.000000e-17

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004340	body mass index
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004329	alcohol drinking
EFO:0004343	waist-hip ratio
EFO:0004833	neutrophil count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5521 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,186 (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

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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
DH376	Inhibition	8.6	pIC50
DO34	Inhibition	8.1	pIC50
LEI105	Inhibition	8.1	pIC50
KT-109	Inhibition	7.09	pIC50
orlistat	Inhibition	7.0	pIC50

ChEMBL bioactivities

37 potent at pChembl≥5 of 37 total, top 37 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.20	IC50	6.31	nM	CHEMBL4470017
7.60	IC50	25.12	nM	CHEMBL4476210
7.40	IC50	40	nM	CHEMBL3764876
7.40	IC50	40	nM	CHEMBL3764017
7.22	IC50	60	nM	CHEMBL158897
7.22	IC50	60	nM	ORLISTAT
7.10	IC50	80	nM	CHEMBL3764093
6.95	IC50	112	nM	CHEMBL3765022
6.84	IC50	146	nM	CHEMBL3765421
6.38	IC50	420	nM	ORLISTAT
5.92	IC50	1200	nM	CHEMBL6046304
5.92	IC50	1200	nM	CHEMBL5981272
5.92	IC50	1200	nM	CHEMBL5898899
5.92	IC50	1200	nM	CHEMBL6039377
5.92	IC50	1200	nM	CHEMBL5742950
5.92	IC50	1200	nM	CHEMBL5862474
5.92	IC50	1200	nM	CHEMBL6019151
5.92	IC50	1200	nM	CHEMBL5805663
5.92	IC50	1200	nM	CHEMBL5960277
5.22	IC50	6000	nM	CHEMBL6012176
5.22	IC50	6000	nM	CHEMBL6039158
5.22	IC50	6000	nM	CHEMBL5749739
5.22	IC50	6000	nM	CHEMBL5976119
5.22	IC50	6000	nM	CHEMBL5897936
5.22	IC50	6000	nM	CHEMBL5806182
5.22	IC50	6000	nM	CHEMBL6033288
5.22	IC50	6000	nM	CHEMBL5750758
5.22	IC50	6000	nM	CHEMBL5919654
5.22	IC50	6000	nM	CHEMBL5797215
5.22	IC50	6000	nM	CHEMBL5912894
5.22	IC50	6000	nM	CHEMBL5960376
5.22	IC50	6000	nM	CHEMBL5844863
5.22	IC50	6000	nM	CHEMBL5887220
5.22	IC50	6000	nM	CHEMBL6056112
5.22	IC50	6000	nM	CHEMBL5940049
5.22	IC50	6000	nM	CHEMBL5939449
5.22	IC50	6000	nM	CHEMBL5792554

PubChem BioAssay actives

10 with measured affinity, of 17 total; 9 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-3-methylpentanoate	1627067: Inhibition of human GST-tagged DAGLbeta catalytic domain expressed in HEK293F cell membranes using EnzChek as substrate preincubated for 5 mins followed by substrate addition by fluorogenic surrogate substrate assay	ic50	0.0063	uM
1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate	1627067: Inhibition of human GST-tagged DAGLbeta catalytic domain expressed in HEK293F cell membranes using EnzChek as substrate preincubated for 5 mins followed by substrate addition by fluorogenic surrogate substrate assay	ic50	0.0251	uM
2-[3-(2,3-dichlorophenyl)-N-[4-(difluoromethoxy)phenyl]sulfonylanilino]acetic acid	1279178: Inhibition of DAGLbeta (unknown origin)	ic50	0.0400	uM
2-[[1-[3-(3,5-dichlorophenyl)phenyl]cyclobutyl]-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl]amino]acetic acid	1279178: Inhibition of DAGLbeta (unknown origin)	ic50	0.0400	uM
Orlistat	409659: Inhibition of human recombinant DAGLbeta overexpressed in african green monkey COS7 cells	ic50	0.0600	uM
(cyclohexylideneamino) N-[6-[(cyclohexylideneamino)oxycarbonylamino]hexyl]carbamate	409659: Inhibition of human recombinant DAGLbeta overexpressed in african green monkey COS7 cells	ic50	0.0600	uM
2-[[1-[3-(2,4-dichlorophenyl)phenyl]cyclobutyl]-(3,4-dichlorophenyl)sulfonylamino]acetic acid	1279178: Inhibition of DAGLbeta (unknown origin)	ic50	0.0800	uM
2-[[4-(difluoromethoxy)phenyl]sulfonyl-[1-[4-[2-(trifluoromethoxy)phenyl]phenyl]cyclobutyl]amino]acetic acid	1279178: Inhibition of DAGLbeta (unknown origin)	ic50	0.1120	uM
2-[[1-[4-(2,4-dichlorophenyl)phenyl]cyclobutyl]-[4-(difluoromethoxy)phenyl]sulfonylamino]acetic acid	1279178: Inhibition of DAGLbeta (unknown origin)	ic50	0.1460	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, increases palmitoylation	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
beta-methylcholine	affects expression	1
1-stearoyl-2-arachidonoylglycerol	increases metabolic processing	1
arachidonyl-2-chloroethylamide	increases expression, affects reaction, decreases reaction	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
GSK5182	decreases reaction, increases expression	1
Irinotecan	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Vehicle Emissions	affects expression, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Caffeine	affects phosphorylation	1
Cannabidiol	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Clozapine	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1227524	Binding	Inhibition of recombinant DAGLbeta 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
CHEMBL5723220	Functional	Affinity Biochemical interaction: (Gel-based competitive ABPP) EUB0002547a DAGLB	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Clinical trials (associated diseases)

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