MOGAT2

Summary

MOGAT2 (monoacylglycerol O-acyltransferase 2, HGNC:23248) is a protein-coding gene on chromosome 11q13.5, encoding 2-acylglycerol O-acyltransferase 2 (Q3SYC2). Involved in glycerolipid synthesis and lipid metabolism.

The protein encoded by this gene is an enzyme that catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. The encoded protein is important in the uptake of dietary fat by the small intestine. This protein forms a complex with diacylglycerol O-acyltransferase 2 in the endoplasmic reticulum, and this complex catalyzes the synthesis of triacylglycerol.

Source: NCBI Gene 80168 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MGAT2-congenital disorder of glycosylation (Definitive, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 246 total — 6 pathogenic, 6 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_025098

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23248
Approved symbol	MOGAT2
Name	monoacylglycerol O-acyltransferase 2
Location	11q13.5
Locus type	gene with protein product
Status	Approved
Aliases	MGAT2, DGAT2L5, FLJ22644
Ensembl gene	ENSG00000166391
Ensembl biotype	protein_coding
OMIM	610270
Entrez	80168

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 TEC

ENST00000198801, ENST00000525093, ENST00000526712, ENST00000624180, ENST00000888392, ENST00000965478

RefSeq mRNA: 1 — MANE Select: NM_025098 NM_025098

CCDS: CCDS8240

Canonical transcript exons

ENST00000198801 — 6 exons

Exon	Start	End
ENSE00000741373	75727435	75727639
ENSE00000797618	75717838	75717979
ENSE00000797619	75719992	75720170
ENSE00001153170	75727970	75728144
ENSE00001336139	75731132	75732953
ENSE00001353021	75728790	75728989

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 99.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4498 / max 241.6331, expressed in 20 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115922	0.4498	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.13	gold quality
mucosa of transverse colon	UBERON:0004991	97.37	gold quality
right lobe of liver	UBERON:0001114	96.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.75	gold quality
rectum	UBERON:0001052	94.14	gold quality
jejunal mucosa	UBERON:0000399	94.04	gold quality
duodenum	UBERON:0002114	92.25	gold quality
liver	UBERON:0002107	91.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.33	gold quality
small intestine	UBERON:0002108	87.61	gold quality
transverse colon	UBERON:0001157	84.70	gold quality
colonic mucosa	UBERON:0000317	81.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	78.59	gold quality
intestine	UBERON:0000160	75.30	gold quality
jejunum	UBERON:0002115	73.49	gold quality
colonic epithelium	UBERON:0000397	72.34	gold quality
vermiform appendix	UBERON:0001154	71.40	gold quality
large intestine	UBERON:0000059	71.20	gold quality
colon	UBERON:0001155	70.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.24	gold quality
left ventricle myocardium	UBERON:0006566	68.99	gold quality
caecum	UBERON:0001153	68.03	gold quality
pancreatic ductal cell	CL:0002079	66.25	silver quality
mammalian vulva	UBERON:0000997	63.53	silver quality
tibialis anterior	UBERON:0001385	61.08	silver quality
upper leg skin	UBERON:0004262	60.35	gold quality
adult mammalian kidney	UBERON:0000082	58.48	gold quality
skin of abdomen	UBERON:0001416	58.21	gold quality
prostate gland	UBERON:0002367	58.19	gold quality
myocardium	UBERON:0002349	58.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting MOGAT2, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-7974	99.24	65.48	1137

Literature-anchored findings (GeneRIF, showing 9)

• MGAT2 may play an important role in dietary fat absorption (PMID:12576479)
• MGAT2 is a monoacylglycerol acyltransferase expressed in the small intestine (PMID:12621063)
• MGAT2 in the intestine plays an indispensable role in enhancing metabolic efficiency but also raise the possibility that MGAT2 in other tissues may contribute to the regulation of energy metabolism. (PMID:23536640)
• MGAT2 functions as a dimeric or tetrameric protein and selectively heterodimerizes with DGAT1 in mammalian cells (PMID:24573674)
• Mogat2(IKO) mice increased energy expenditure although to a lesser degree than Mogat2(-/-) mice and were protected against diet-induced weight gain and associated comorbidities (PMID:24784138)
• The described cell-based assay adds a new methodology for the development and evaluation of MGAT2 inhibitors for the treatment of obesity and type 2 diabetes (PMID:25598079)
• Diacylglycerol acyltransferase-2 and monoacylglycerol acyltransferase-2 are ubiquitinated proteins that are degraded by the 26S proteasome (PMID:27531967)
• The use of 1-oleoyl-glycerol-d5 and (U13)C-TG oil followed by LC/ESI/MS/MS detection of stable-isotopic labeled DAG, TG, or glycerol provides a wide range of applications to study pathophysiological regulation of the monoacylglycerol pathway and MGAT2 activity. (PMID:27665677)
• Fatty acid metabolism prognostic signature predicts tumor immune microenvironment and immunotherapy, and identifies tumorigenic role of MOGAT2 in lung adenocarcinoma. (PMID:39478862)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	mogat2	ENSDARG00000019228
mus_musculus	Mogat2	ENSMUSG00000052396
rattus_norvegicus	Mogat2	ENSRNOG00000027228
drosophila_melanogaster	CG1941	FBGN0033214
drosophila_melanogaster	Dgat2	FBGN0033215
drosophila_melanogaster	CG1946	FBGN0033216
caenorhabditis_elegans		WBGENE00010296
caenorhabditis_elegans		WBGENE00019464
caenorhabditis_elegans		WBGENE00020910
caenorhabditis_elegans		WBGENE00021818

Paralogs (6): DGAT2 (ENSG00000062282), MOGAT3 (ENSG00000106384), MOGAT1 (ENSG00000124003), AWAT2 (ENSG00000147160), DGAT2L6 (ENSG00000184210), AWAT1 (ENSG00000204195)

Protein

Protein identifiers

2-acylglycerol O-acyltransferase 2 — Q3SYC2 (reviewed: Q3SYC2)

Alternative names: Acyl-CoA:monoacylglycerol acyltransferase 2, Diacylglycerol O-acyltransferase candidate 5, Diacylglycerol acyltransferase 2-like protein 5, Monoacylglycerol O-acyltransferase 2

All UniProt accessions (1): Q3SYC2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in glycerolipid synthesis and lipid metabolism. Catalyzes the formation of diacylglycerol, the precursor of triacylglycerol, by transferring the acyl chain of a fatty acyl-CoA to a monoacylglycerol. Plays a central role in absorption of dietary fat in the small intestine by catalyzing the resynthesis of triacylglycerol in enterocytes. Has a preference toward monoacylglycerols containing unsaturated fatty acids in an order of C18:3 > C18:2 > C18:1 > C18:0 at sn-2. Able to use 1-monoalkylglycerol (1-MAkG, 1-O-alkylglycerol) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG, 1-O-alkyl-3-acylglycerol or 1-O-alkyl-2-acylglycerol) and subsequently, with lower efficiency, may add another acyl chain producing monoalkyl-diacylglycerol (MADAG, 1-O-alkyl-2,3-diacylglycerol). Possesses weak but significant activity with diacylglycerol as substrate, producing triacylglycerol (triacyl-sn-glycerol).

Subcellular location. Endoplasmic reticulum membrane. Cytoplasm. Perinuclear region.

Tissue specificity. Highly expressed in liver, small intestine, colon, stomach and kidney.

Activity regulation. Inhibited by oleic acid and sphingosine, while it is stimulated by phosphatidylcholine, phosphatidylserine and phosphatidic acid.

Pathway. Glycerolipid metabolism; triacylglycerol biosynthesis.

Similarity. Belongs to the diacylglycerol acyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q3SYC2-1	1	yes
Q3SYC2-2	2
Q3SYC2-3	3, MGAT2V, Trunc

RefSeq proteins (1): NP_079374* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007130	DAGAT	Family

Pfam: PF03982

Enzyme classification (BRENDA):

• EC 2.3.1.22 — 2-acylglycerol O-acyltransferase (BRENDA: 15 organisms, 98 substrates, 122 inhibitors, 13 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-OLEOYL-SN-GLYCEROL	0.0056–0.0148	2
OLEOYL-COA	0.0083–0.0094	2
PALMITOYL-COA	0.0065–0.0175	2
1-PALMITOYLGLYCEROL	0.0164	1
2-OLEOYL-SN-GLYCEROL	0.16	1
LINOLEOYL-COA	0.047	1
SN-2-MONOLINOLENOYLGLYCEROL	0.0071	1
SN-2-MONOLINOLEOYLGLYCEROL	0.011	1
SN-2-MONOOLEOYLGLYCEROL	0.021	1
STEAROYL-COA	0.0257	1

Catalyzed reactions (Rhea), 12 shown:

• an acyl-CoA + a 1,2-diacyl-sn-glycerol = a triacyl-sn-glycerol + CoA (RHEA:10868)
• a 2-acylglycerol + an acyl-CoA = a 1,2-diacylglycerol + CoA (RHEA:16741)
• a 2-acylglycerol + an acyl-CoA = a 1,2-diacyl-sn-glycerol + CoA (RHEA:32947)
• 1-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoyl-CoA = 1,2-di-(9Z-octadecenoyl)-glycerol + CoA (RHEA:37915)
• 1-decanoylglycerol + (9Z)-octadecenoyl-CoA = 1-decanoyl-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38019)
• 1-dodecanoylglycerol + (9Z)-octadecenoyl-CoA = 1-dodecanoyl-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38115)
• 1-tetradecanoylglycerol + (9Z)-octadecenoyl-CoA = 1-tetradecanoyl-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38119)
• 1-hexadecanoylglycerol + (9Z)-octadecenoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38123)
• 1-octadecanoylglycerol + (9Z)-octadecenoyl-CoA = 1-octadecanoyl-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38127)
• 1-(9Z,12Z-octadecadienoyl)-glycerol + (9Z)-octadecenoyl-CoA = 1-(9Z,12Z-octadecadienoyl)-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38131)
• 1-(9Z,12Z,15Z-octadecatrienoyl)-glycerol + (9Z)-octadecenoyl-CoA = 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38135)
• 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + (9Z)-octadecenoyl-CoA = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38139)

UniProt features (12 total): transmembrane region 3, splice variant 3, sequence variant 3, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3SYC2-F1	94.86	0.89

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-75109	Triglyceride biosynthesis
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8979227	Triglyceride metabolism

MSigDB gene sets: 569 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, RNGTGGGC_UNKNOWN, GOBP_DIGESTION, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, KEGG_N_GLYCAN_BIOSYNTHESIS, chr11q13, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, ONKEN_UVEAL_MELANOMA_UP

GO Biological Process (6): glycerol metabolic process (GO:0006071), monoacylglycerol biosynthetic process (GO:0006640), diacylglycerol biosynthetic process (GO:0006651), triglyceride biosynthetic process (GO:0019432), intestinal absorption (GO:0050892), lipid metabolic process (GO:0006629)

GO Molecular Function (6): 2-acylglycerol O-acyltransferase activity (GO:0003846), diacylglycerol O-acyltransferase activity (GO:0004144), acetyltransferase activity (GO:0016407), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), perinuclear endoplasmic reticulum membrane (GO:1990578), cytoplasm (GO:0005737), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Triglyceride metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acylglycerol biosynthetic process	3
cellular anatomical structure	3
acylglycerol O-acyltransferase activity	2
cytoplasm	2
organelle membrane	2
carbohydrate metabolic process	1
polyol metabolic process	1
monoacylglycerol metabolic process	1
diacylglycerol metabolic process	1
triglyceride metabolic process	1
digestive system process	1
primary metabolic process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity	1
transferase activity	1
endomembrane system	1
intracellular membrane-bounded organelle	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum membrane	1
perinuclear endoplasmic reticulum	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOGAT2	DGAT1	O75907	926
MOGAT2	CANX	P27824	525
MOGAT2	FABP2	P12104	514
MOGAT2	AGPAT1	Q99943	507
MOGAT2	AGPAT3	Q9NRZ7	493
MOGAT2	MGAT1	P26572	459
MOGAT2	AASDH	Q4L235	458
MOGAT2	AADAC	P22760	455
MOGAT2	AGPAT2	O15120	441
MOGAT2	MRPS28	Q9Y2Q9	441
MOGAT2	GPAT3	Q53EU6	430
MOGAT2	TMEM269	A0A1B0GVZ9	415
MOGAT2	GPAT4	Q86UL3	414
MOGAT2	SLC27A4	Q6P1M0	408
MOGAT2	KLF6	Q99612	386

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MOGAT2	DDI2	psi-mi:“MI:0915”(physical association)	0.400
MOGAT2	CLCN3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): NME2P1 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), CLCN3 (Affinity Capture-MS), MOGAT2 (Positive Genetic), MOGAT2 (Protein-peptide)

ESM2 similar proteins: A0A0M4FCN7, A1A442, A8DZE7, F4IF99, K7K424, K7PEY4, O80437, P52581, Q0DWQ1, Q0VCR6, Q1HAQ0, Q1LWG4, Q1PET6, Q32L94, Q3SYC2, Q3TFD2, Q4V9F0, Q5FVP8, Q5R7E8, Q5XF03, Q5ZJD8, Q6L5F5, Q6P342, Q6PAZ3, Q70VZ7, Q70VZ8, Q7L5N7, Q80W94, Q8BYI6, Q8K3K7, Q8K4X7, Q8L4Y2, Q8L7M0, Q8S8S2, Q924S1, Q94AH8, Q94AS5, Q96MH6, Q96PD7, Q9ASU1

Diamond homologs: A2ADU8, A2ADU9, A6QP72, K7K424, O74850, Q08650, Q28C88, Q2KHS5, Q3KPP4, Q3SYC2, Q4V9F0, Q54GC1, Q58HT5, Q5FVP8, Q5M7F4, Q5M8H5, Q6E1M8, Q6E213, Q6P342, Q6PAZ3, Q6ZPD8, Q70VZ7, Q70VZ8, Q75BY0, Q80W94, Q86VF5, Q91ZV4, Q96PD6, Q96PD7, Q96UY1, Q96UY2, Q9ASU1, Q9DCV3, A1A442, Q9ZVN2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TFEB	“up-regulates quantity by expression”	MOGAT2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	6
Uncertain significance	193
Likely benign	22
Benign	8

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
617657	NM_002408.4(MGAT2):c.753dup (p.Ala252fs)	Pathogenic
617658	NM_002408.4(MGAT2):c.91C>T (p.Gln31Ter)	Pathogenic
617661	NM_002408.4(MGAT2):c.799G>C (p.Asp267His)	Pathogenic
6990	NM_002408.4(MGAT2):c.785A>G (p.His262Arg)	Pathogenic
6991	NM_002408.4(MGAT2):c.952A>G (p.Asn318Asp)	Pathogenic
6992	NM_002408.4(MGAT2):c.1017T>A (p.Cys339Ter)	Pathogenic
30270	NM_002408.4(MGAT2):c.711G>C (p.Lys237Asn)	Likely pathogenic
3061920	NM_002408.4(MGAT2):c.1085G>A (p.Trp362Ter)	Likely pathogenic
3065025	NM_002408.4(MGAT2):c.1199_1202del (p.Asn400fs)	Likely pathogenic
489288	NM_002408.4(MGAT2):c.745C>T (p.Arg249Ter)	Likely pathogenic
596219	NM_002408.4(MGAT2):c.1006_1009del (p.Asp336fs)	Likely pathogenic
817419	NM_002408.4(MGAT2):c.346dup (p.Arg116fs)	Likely pathogenic

SpliceAI

1217 predictions. Top by Δscore:

Variant	Effect	Δscore
11:75719988:CCAGC:C	acceptor_loss	1.0000
11:75719989:CAGCC:C	acceptor_loss	1.0000
11:75719990:A:AG	acceptor_gain	1.0000
11:75719990:A:AT	acceptor_loss	1.0000
11:75719990:AGCC:A	acceptor_gain	1.0000
11:75719991:G:GC	acceptor_gain	1.0000
11:75719991:G:GT	acceptor_loss	1.0000
11:75719991:GCC:G	acceptor_gain	1.0000
11:75719991:GCCG:G	acceptor_gain	1.0000
11:75719991:GCCGA:G	acceptor_gain	1.0000
11:75720166:TCTCG:T	donor_gain	1.0000
11:75720169:CGGT:C	donor_loss	1.0000
11:75720171:G:GG	donor_gain	1.0000
11:75720171:GTG:G	donor_loss	1.0000
11:75720172:T:A	donor_loss	1.0000
11:75727968:AG:A	acceptor_gain	1.0000
11:75727969:GG:G	acceptor_gain	1.0000
11:75727969:GGGTT:G	acceptor_gain	1.0000
11:75728116:GGC:G	donor_gain	1.0000
11:75728143:GG:G	donor_gain	1.0000
11:75728144:GG:G	donor_gain	1.0000
11:75728160:G:GT	donor_gain	1.0000
11:75728160:G:T	donor_gain	1.0000
11:75728784:CTCCA:C	acceptor_loss	1.0000
11:75728785:TCCAG:T	acceptor_loss	1.0000
11:75728786:CCAG:C	acceptor_loss	1.0000
11:75728788:A:AG	acceptor_gain	1.0000
11:75728788:AG:A	acceptor_gain	1.0000
11:75728789:G:GG	acceptor_gain	1.0000
11:75728789:G:GT	acceptor_loss	1.0000

AlphaMissense

2175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:75728119:T:C	F209L	0.991
11:75728121:C:A	F209L	0.991
11:75728121:C:G	F209L	0.991
11:75728815:T:C	F226L	0.985
11:75728817:C:A	F226L	0.985
11:75728817:C:G	F226L	0.985
11:75727486:C:G	H108D	0.984
11:75727600:T:C	F146L	0.984
11:75727602:C:A	F146L	0.984
11:75727602:C:G	F146L	0.984
11:75727619:G:T	R152I	0.983
11:75720159:T:C	F87L	0.982
11:75720161:C:A	F87L	0.982
11:75720161:C:G	F87L	0.982
11:75727496:G:A	G111E	0.981
11:75728120:T:C	F209S	0.979
11:75728063:A:T	E190V	0.976
11:75728801:T:A	V221E	0.975
11:75731225:T:C	L315P	0.975
11:75731227:T:C	F316L	0.975
11:75731229:C:A	F316L	0.975
11:75731229:C:G	F316L	0.975
11:75727496:G:T	G111V	0.974
11:75727619:G:C	R152T	0.974
11:75728804:C:A	P222Q	0.974
11:75731216:T:C	L312P	0.974
11:75731273:T:C	L331S	0.974
11:75728051:G:A	G186E	0.973
11:75727546:T:C	F128L	0.972
11:75727548:C:A	F128L	0.972

dbSNP variants (sampled 300 via entrez): RS1000350459 (11:75725328 C>T), RS1000414840 (11:75719817 C>T), RS1000473354 (11:75724001 A>G), RS1000651791 (11:75725033 T>G), RS1000787940 (11:75733431 C>A,T), RS1000889762 (11:75727824 A>G), RS1001203613 (11:75721341 G>A), RS1001377206 (11:75722666 C>G,T), RS1001904781 (11:75731886 C>A,G,T), RS1001990669 (11:75726889 G>C), RS1002187422 (11:75716562 T>C), RS1002359967 (11:75727898 T>C), RS1002504284 (11:75732991 C>T), RS1002801767 (11:75722016 G>A), RS1002837071 (11:75731041 A>C,G)

Disease associations

OMIM: gene MIM:610270 | disease phenotypes: MIM:212066

GenCC curated gene-disease

Disease	Classification	Inheritance
MGAT2-congenital disorder of glycosylation	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MGAT2-congenital disorder of glycosylation	Moderate	AR

Mondo (1): MGAT2-congenital disorder of glycosylation (MONDO:0008908)

Orphanet (1): MGAT2-CDG (Orphanet:79329)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002223_46	HDL cholesterol	1.000000e-08
GCST002444_6	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	5.000000e-06
GCST004232_60	HDL cholesterol levels	5.000000e-11
GCST004403_6	Bone fracture in osteoporosis	5.000000e-06
GCST006005_17	High density lipoprotein cholesterol levels	8.000000e-09
GCST006585_2226	Blood protein levels	1.000000e-09
GCST009391_1342	Metabolite levels	6.000000e-06
GCST010241_168	Apolipoprotein A1 levels	8.000000e-62
GCST010242_465	HDL cholesterol levels	8.000000e-41
GCST011348_29	High density lipoprotein cholesterol levels	5.000000e-11
GCST90011900_70	Serum alkaline phosphatase levels	8.000000e-09
GCST90013406_231	Liver enzyme levels (alkaline phosphatase)	2.000000e-16

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0010362	lysophosphatidylcholine 20:3 measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535752	Congenital disorder of glycosylation type 2A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2439944 (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: 10 (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
CHEMBL5418882	BMS-986172	1	10

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.3.1.- Acyltransferases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
BMS-986172	Inhibition	8.34	pIC50
BMS-963272	Inhibition	8.15	pIC50

Binding affinities (BindingDB)

149 measured of 149 human assays (149 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(4-tert-butylphenyl)-5-[[2-fluoro-4-[(Z)-oct-6-enoxy]phenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	2 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[4-(3-cyclopentylpropoxy)-2-fluorophenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	4 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(6-tert-butyl-3-pyridinyl)propan-2-yl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	5 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[(2-fluoro-4-octoxyphenyl)sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	7 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[2-fluoro-4-(5-phenylpentoxy)phenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	10 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-propan-2-yl-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	10 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(6-tert-butyl-3-pyridinyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	13 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(2-tert-butyl-4-pyridinyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	13 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(4-tert-butylphenyl)-2-methylpropan-2-yl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	14 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(6-tert-butyl-3-pyridinyl)ethyl]-N-[2-fluoro-4-(5-phenylpentoxy)phenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	14 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-[(1S)-1-[4-[[2-(2-chlorophenyl)morpholin-4-yl]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide	IC50	16 nM	US-8993568: Morpholinyl derivatives useful as MOGAT-2 inhibitors
N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-[[1-(4-methylphenyl)pyrazol-4-yl]methyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	16 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[2-fluoro-4-(2-pyridin-2-ylethoxy)phenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	23 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-[2-fluoro-4-[3-(oxan-4-yl)propyl]phenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	24 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-[2-fluoro-4-(5-phenylpentoxy)phenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	24 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(4-tert-butylphenyl)propan-2-yl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	25 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[(6-tert-butyl-3-pyridinyl)methyl]-N-(2-fluoro-4-octoxyphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	26 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(4-tert-butylphenyl)propan-2-yl]-N-(2-fluoro-4-hexoxyphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	26 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[4-(3-cyclohexylpropoxy)-2-fluorophenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	26 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
(S)-3-(5-Oxo-4,5-dihydro-1H-tetrazol-1-yl)-4-(p-tolyl)-6-(4-(4,4,4-trifluorobutoxy)phenyl)-6-(trifluoromethyl)-5,6-dihydropyridin-2(1H)-one	IC50	27 nM	US-11479538: Tetrazolone-substituted dihydropyridinone MGAT2 inhibitors
2-[2-(4-tert-butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	28 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[(2-fluoro-4-heptoxyphenyl)sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	28 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-[4-(2-cyclopentylethoxy)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	29 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[4-(2-cyclohexylethoxy)-2-fluorophenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	29 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[2-fluoro-4-(4-phenylbutoxy)phenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	30 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[(6-tert-butyl-3-pyridinyl)methyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	31 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[(6-tert-butyl-3-pyridinyl)methyl]-N-(2-fluoro-4-heptylphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	31 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(4-tert-butylphenyl)propan-2-yl]-N-(2-fluoro-4-heptylphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	31 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[2-fluoro-4-(4-phenoxybutoxy)phenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	33 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(2-tert-butylpyrimidin-5-yl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	34 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-(2-fluoro-4-heptylphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	35 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-[4-[3-(benzenesulfonyl)propoxy]-2-fluorophenyl]-2-[2-(4-tert-butylphenyl)ethyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	35 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[(6-tert-butyl-3-pyridinyl)methyl]-N-[2-fluoro-4-(5-phenylpentoxy)phenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	36 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-[4-(3-cyclohexylpropoxy)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	39 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-[(1S)-2,2,2-trifluoro-1-[4-[[2-(4-fluorophenyl)morpholin-4-yl]methyl]phenyl]ethyl]methanesulfonamide	IC50	40 nM	US-8993568: Morpholinyl derivatives useful as MOGAT-2 inhibitors
2-[2-(5-tert-butylpyrimidin-2-yl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	40 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-(2-fluoro-4-heptoxyphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	40 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[(2-tert-butyl-1,3-thiazol-5-yl)methyl]-N-(2-fluoro-4-heptylphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	42 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(4-tert-butylphenyl)propan-2-yl]-N-[2-fluoro-4-(5-phenylpentoxy)phenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	42 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[(2-fluoro-4-hexoxyphenyl)sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	43 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[1-(4-tert-butylphenyl)propan-2-yl]-N-[2-fluoro-4-[2-(oxan-4-yl)ethoxy]phenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	44 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-[[2,5-dimethyl-1-[3-(trifluoromethyl)phenyl]pyrrol-3-yl]methyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	45 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-(2-fluoro-4-octoxyphenyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	45 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(5-tert-butylpyrazin-2-yl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	46 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-[2-[5-(trifluoromethyl)-2-pyridinyl]ethyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	46 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[(2-tert-butyl-1,3-thiazol-5-yl)methyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	49 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	51 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[(2-tert-butylpyrimidin-5-yl)methyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	52 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
2-[2-(4-tert-butylphenyl)ethyl]-N-[2-fluoro-4-(5-phenylpentyl)phenyl]-3,4-dihydro-1H-isoquinoline-6-sulfonamide	IC50	53 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound
N-(4-tert-butylphenyl)-5-[[2-fluoro-4-(3-phenylpropoxy)phenyl]sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	IC50	56 nM	US-9035059: Nitrogen-containing condensed heterocyclic compound

ChEMBL bioactivities

280 potent at pChembl≥5 of 285 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.60	IC50	0.25	nM	CHEMBL5687004
9.38	IC50	0.42	nM	CHEMBL5687021
9.16	IC50	0.69	nM	CHEMBL5687051
9.00	IC50	1	nM	CHEMBL5434664
9.00	IC50	1	nM	CHEMBL3581716
8.70	IC50	2	nM	CHEMBL2441597
8.70	IC50	2	nM	CHEMBL3655055
8.70	IC50	2	nM	CHEMBL5422037
8.70	IC50	2	nM	CHEMBL5415437
8.70	IC50	2	nM	CHEMBL5424834
8.70	IC50	2	nM	CHEMBL4542050
8.68	IC50	2.1	nM	CHEMBL5686988
8.52	IC50	3	nM	CHEMBL5971914
8.47	IC50	3.4	nM	CHEMBL3581734
8.43	IC50	3.7	nM	CHEMBL5687022
8.42	IC50	3.8	nM	CHEMBL3325734
8.40	IC50	4	nM	CHEMBL3134097
8.40	IC50	4	nM	CHEMBL3639539
8.40	IC50	4	nM	CHEMBL3655064
8.39	IC50	4.1	nM	CHEMBL5686997
8.30	IC50	5	nM	CHEMBL3655062
8.30	IC50	5	nM	CHEMBL5411014
8.30	IC50	5	nM	CHEMBL5406388
8.30	IC50	5	nM	CHEMBL5777679
8.30	IC50	5	nM	BMS-986172
8.30	IC50	5	nM	CHEMBL5971575
8.30	IC50	5	nM	CHEMBL5787924
8.21	IC50	6.2	nM	CHEMBL5687019
8.15	IC50	7	nM	CHEMBL2441598
8.15	IC50	7	nM	CHEMBL2441600
8.15	IC50	7	nM	CHEMBL3134101
8.15	IC50	7	nM	CHEMBL3134099
8.15	IC50	7	nM	CHEMBL3655036
8.11	IC50	7.8	nM	TP-020
8.10	IC50	8	nM	CHEMBL2441597
8.10	IC50	8	nM	CHEMBL5435045
8.10	IC50	8	nM	CHEMBL5401316
8.10	IC50	8	nM	CHEMBL5948973
8.09	IC50	8.2	nM	CHEMBL5687034
8.05	IC50	9	nM	CHEMBL2441598
8.05	IC50	9	nM	CHEMBL3134098
8.05	IC50	9	nM	CHEMBL5413599
8.05	IC50	9	nM	CHEMBL5812278
8.00	IC50	10	nM	CHEMBL3134084
8.00	IC50	10	nM	CHEMBL2376303
8.00	IC50	10	nM	CHEMBL3655042
8.00	IC50	10	nM	CHEMBL3655069
8.00	IC50	10	nM	CHEMBL5407931
8.00	IC50	10	nM	CHEMBL5976649
8.00	IC50	10	nM	CHEMBL5966214

PubChem BioAssay actives

72 with measured affinity, of 74 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
N-(4-chloro-2,6-difluorophenyl)-7-(2-oxopyrrolidin-1-yl)-1-[4-[4-(trifluoromethyl)phenyl]phenyl]-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0003	uM
N-(4-chloro-2,6-difluorophenyl)-1-[5-[2-fluoro-4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-7-(2-oxopyrrolidin-1-yl)-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0004	uM
N-(4-chloro-2,6-difluorophenyl)-7-(2-oxopyrrolidin-1-yl)-1-[5-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0007	uM
N-[5-[(2,4-difluorophenyl)sulfamoyl]-1-(2-phenylethyl)-2,3-dihydroindol-7-yl]acetamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0010	uM
6-[2-fluoro-4-(6,6,6-trifluorohexoxy)phenyl]-4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0010	uM
4-[2-(dimethylamino)-1,3-thiazol-5-yl]-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0020	uM
4-(5-cyclopropylthiophen-2-yl)-3-(2H-tetrazol-5-yl)-6-[4-(6,6,6-trifluorohexoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0020	uM
4-(5-ethylthiophen-2-yl)-3-(2H-tetrazol-5-yl)-6-[4-(6,6,6-trifluorohexoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0020	uM
(2S)-4-(4-methylphenyl)-N-(1,2-oxazol-5-yl)-6-oxo-2-[4-(4,4,4-trifluorobutoxy)phenyl]-2-(trifluoromethyl)-1,3-dihydropyridine-5-carboxamide	777476: Inhibition of human MGAT2 by LC/MS assay	ic50	0.0020	uM
N-(4-chloro-2,6-difluorophenyl)-1-[5-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]pyrimidin-2-yl]-7-(2-oxopyrrolidin-1-yl)-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0021	uM
5-[(2,4-difluorophenyl)sulfamoyl]-7-(2-oxopyrrolidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-2,3-dihydroindole-1-carboxamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0034	uM
N-(4-chloro-2,6-difluorophenyl)-1-[5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]pyrimidin-2-yl]-7-(2-oxoimidazolidin-1-yl)-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0037	uM
N-[(1S)-1-[4-[[[(3S)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl]methylamino]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide;hydrochloride	1188780: Inhibition of human MoGAT-2 expressed in human Caco2 cells assessed as inhibition of 2-O-Hexadecylglycerol hydrolysis pretreated for 30 mins by LC-MS analysis	ic50	0.0038	uM
[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl] 5-[(2,4-difluorophenyl)sulfamoyl]-7-(2-oxopyrrolidin-1-yl)-2,3-dihydroindole-1-carboxylate	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0041	uM
N-cyclopropylsulfonyl-6-[2-fluoro-4-(6,6,6-trifluorohexoxy)phenyl]-4-(4-methylphenyl)-2-oxo-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0050	uM
6-[2-fluoro-4-(6,6,6-trifluorohexoxy)phenyl]-4-(4-methylphenyl)-N-methylsulfonyl-2-oxo-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0050	uM
N-(4-chloro-2,6-difluorophenyl)-7-(2-oxopyrrolidin-1-yl)-1-[5-[4-(trifluoromethyl)pyrazol-1-yl]pyrimidin-2-yl]-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0062	uM
N-(4-methoxyphenyl)-4-(4-methylphenyl)-6-oxo-2-[4-(4,4,4-trifluorobutoxy)phenyl]-2-(trifluoromethyl)-1,3-dihydropyridine-5-carboxamide	777476: Inhibition of human MGAT2 by LC/MS assay	ic50	0.0070	uM
(2S)-4-(4-methylphenyl)-6-oxo-N-[4-(2H-tetrazol-5-yl)phenyl]-2-[4-(4,4,4-trifluorobutoxy)phenyl]-2-(trifluoromethyl)-1,3-dihydropyridine-5-carboxamide	777476: Inhibition of human MGAT2 by LC/MS assay	ic50	0.0070	uM
N-(4-chloro-2,6-difluorophenyl)-1-[5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]pyrimidin-2-yl]-7-(2-oxopyrrolidin-1-yl)-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0078	uM
6-[2-chloro-4-(4,4,4-trifluorobutoxy)phenyl]-4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0080	uM
4-(5-ethylthiophen-2-yl)-3-(2H-tetrazol-5-yl)-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0080	uM
N-(4-chloro-2,6-difluorophenyl)-7-(2-oxopyrrolidin-1-yl)-1-[5-[3-(trifluoromethyl)pyrazol-1-yl]pyrimidin-2-yl]-2,3-dihydroindole-5-sulfonamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0082	uM
6-[2-fluoro-4-(5,5,5-trifluoropentoxy)phenyl]-4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0090	uM
N-[4-(4-methylphenyl)-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-3-yl]-1,2-oxazole-5-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0100	uM
6-[2-ethoxy-4-(4,4,4-trifluorobutoxy)phenyl]-4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0140	uM
6-[2-fluoro-4-(4,4,4-trifluorobutoxy)phenyl]-4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0160	uM
4-[1-(cyclopropylmethyl)pyrazol-3-yl]-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0170	uM
4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-6-[4-(4,4,4-trifluorobutoxy)-2-(trifluoromethyl)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0170	uM
[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl] 5-[(4-chloro-2,6-difluorophenyl)sulfamoyl]-7-(2-oxopyrrolidin-1-yl)-2,3-dihydroindole-1-carboxylate	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0190	uM
4-(5-ethylthiophen-2-yl)-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0210	uM
4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0210	uM
4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-6-[4-(6,6,6-trifluorohexoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0240	uM
4-(5-cyclopropylthiophen-2-yl)-3-(2H-tetrazol-5-yl)-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0250	uM
4-(4-methylphenyl)-N-methylsulfonyl-2-oxo-6-[4-(6,6,6-trifluorohexoxy)phenyl]-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0270	uM
6-[4-(4,4-dimethylcyclohexen-1-yl)phenyl]-4-(4-methylphenyl)-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0270	uM
5-[(4-chloro-2,6-difluorophenyl)sulfamoyl]-7-(2-oxopyrrolidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-2,3-dihydroindole-1-carboxamide	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0300	uM
N-cyclopropylsulfonyl-4-(4-methylphenyl)-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0320	uM
N-cyclopropylsulfonyl-6-[2-fluoro-4-(4,4,4-trifluorobutoxy)phenyl]-4-(4-methylphenyl)-2-oxo-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0380	uM
[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl] 5-[[2-fluoro-4-(trifluoromethyl)phenyl]sulfamoyl]-7-(2-oxopyrrolidin-1-yl)-2,3-dihydroindole-1-carboxylate	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0420	uM
4-(1-ethylpyrazol-3-yl)-3-(2H-tetrazol-5-yl)-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0440	uM
3-methyl-N-[4-(4-methylphenyl)-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-3-yl]-1,2-oxazole-5-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0560	uM
4-(1-cyclopropylpyrazol-3-yl)-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]-1H-pyridine-3-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0590	uM
[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl] 7-(2-oxopyrrolidin-1-yl)-5-[(2,4,6-trifluorophenyl)sulfamoyl]-2,3-dihydroindole-1-carboxylate	2171981: Inhibition of N-terminal FLAG-tagged full-length human MGAT2 expressed in human FreeStyle 293-F cell membrane using 13Cx18oleoyl-CoA and 2-oleoyl-glycerol as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire mass spectrometric analysis	ic50	0.0750	uM
N-[4-(4-methylphenyl)-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-3-yl]-2H-tetrazole-5-carboxamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.0800	uM
N-[(1R)-1-[4-[[(1-phenylpyrrolidin-3-yl)amino]methyl]phenyl]ethyl]methanesulfonamide;hydrochloride	1188780: Inhibition of human MoGAT-2 expressed in human Caco2 cells assessed as inhibition of 2-O-Hexadecylglycerol hydrolysis pretreated for 30 mins by LC-MS analysis	ic50	0.1050	uM
4-methoxy-N-[4-(4-methylphenyl)-2-oxo-6-[4-(4,4,4-trifluorobutoxy)phenyl]-1H-pyridin-3-yl]benzamide	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.1060	uM
5-(2-ethyltetrazol-5-yl)-4-(4-methylphenyl)-2-[4-(4,4,4-trifluorobutoxy)phenyl]-2-(trifluoromethyl)-1,3-dihydropyridin-6-one	777476: Inhibition of human MGAT2 by LC/MS assay	ic50	0.1210	uM
N-(4-tert-butylphenyl)-5-[(2-fluoro-4-pentoxyphenyl)sulfamoyl]-1,3-dihydroisoindole-2-carboxamide	1240478: Inhibition of human recombinant MGAT2 assessed as reduction in enzyme-mediated deacylation of oleoyl-CoA incubated for 20 mins by CPM dye based fluorescence assay	ic50	0.1470	uM
4-(1-ethylpyrazol-3-yl)-3-(2H-tetrazol-5-yl)-6-[4-(6,6,6-trifluorohexoxy)phenyl]-1H-pyridin-2-one	1970946: Inhibition of human MGAT2 by LC-MS analysis	ic50	0.1480	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Nickel	decreases expression	2
methyleugenol	decreases expression	1
terbufos	increases methylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
Acetaminophen	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Quercetin	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2446068	Binding	Inhibition of human MGAT2 by LC/MS assay	Fighting Obesity and Metabolic Disorders with MGAT-2 Inhibitors. — ACS Med Chem Lett

Clinical trials (associated diseases)

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