MOGAT3

Summary

MOGAT3 (monoacylglycerol O-acyltransferase 3, HGNC:23249) is a protein-coding gene on chromosome 7q22.1, encoding 2-acylglycerol O-acyltransferase 3 (Q86VF5). Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA.

Acyl-CoA:monoacylglycerol acyltransferase (MOGAT; EC 2.3.1.22) catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA (Cheng et al., 2003 [PubMed 12618427]).

Source: NCBI Gene 346606 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 72 total
• Druggable target: yes
• MANE Select transcript: NM_178176

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23249
Approved symbol	MOGAT3
Name	monoacylglycerol O-acyltransferase 3
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DC7, MGAT3, DGAT2L2
Ensembl gene	ENSG00000106384
Ensembl biotype	protein_coding
OMIM	610184
Entrez	346606

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000223114, ENST00000379423, ENST00000440203, ENST00000649999, ENST00000893927, ENST00000893928, ENST00000950440

RefSeq mRNA: 2 — MANE Select: NM_178176 NM_001287147, NM_178176

CCDS: CCDS5714, CCDS75643

Canonical transcript exons

ENST00000223114 — 7 exons

Exon	Start	End
ENSE00000712194	101196187	101196389
ENSE00000712199	101198191	101198365
ENSE00000712205	101198626	101198830
ENSE00001339316	101200234	101200304
ENSE00001339317	101200408	101200515
ENSE00001339321	101200746	101201036
ENSE00001804249	101195007	101196100

Expression profiles

Bgee: expression breadth broad, 49 present calls, max score 95.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3277 / max 103.9154, expressed in 55 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85310	0.3163	52
204615	0.0114	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.06	gold quality
ileal mucosa	UBERON:0000331	93.23	gold quality
rectum	UBERON:0001052	86.77	gold quality
right lobe of liver	UBERON:0001114	86.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.95	gold quality
duodenum	UBERON:0002114	83.22	gold quality
small intestine	UBERON:0002108	82.38	gold quality
transverse colon	UBERON:0001157	81.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.76	silver quality
jejunal mucosa	UBERON:0000399	74.45	gold quality
liver	UBERON:0002107	72.63	gold quality
intestine	UBERON:0000160	70.02	gold quality
colonic mucosa	UBERON:0000317	69.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	67.68	silver quality
vermiform appendix	UBERON:0001154	66.40	gold quality
large intestine	UBERON:0000059	65.79	gold quality
colon	UBERON:0001155	65.71	gold quality
colonic epithelium	UBERON:0000397	64.65	gold quality
tibialis anterior	UBERON:0001385	61.60	silver quality
caecum	UBERON:0001153	60.72	gold quality
pancreatic ductal cell	CL:0002079	60.28	silver quality
jejunum	UBERON:0002115	59.13	gold quality
adult mammalian kidney	UBERON:0000082	57.44	gold quality
metanephros cortex	UBERON:0010533	55.17	gold quality
epithelial cell of pancreas	CL:0000083	54.68	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
smooth muscle tissue	UBERON:0001135	54.32	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting MOGAT3, 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-4283	100.00	66.42	2097
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-3674	97.01	68.86	1171

Literature-anchored findings (GeneRIF, showing 1)

• MGAT3 encodes a approximately 36-kDa transmembrane protein that is highly homologous to MGAT1 and -2 and is expressed in the human gastrointestinal tract with the highest level found in the ileum (PMID:12618427)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mogat3b	ENSDARG00000003635
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), MOGAT1 (ENSG00000124003), AWAT2 (ENSG00000147160), MOGAT2 (ENSG00000166391), DGAT2L6 (ENSG00000184210), AWAT1 (ENSG00000204195)

Protein

Protein identifiers

2-acylglycerol O-acyltransferase 3 — Q86VF5 (reviewed: Q86VF5)

Alternative names: Acyl-CoA:monoacylglycerol acyltransferase 3, Diacylglycerol O-acyltransferase candidate 7, Diacylglycerol acyltransferase 2-like protein 7, Monoacylglycerol O-acyltransferase 3

All UniProt accessions (1): Q86VF5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. Also able to catalyze the terminal step in triacylglycerol synthesis by using diacylglycerol and fatty acyl-CoA as substrates. Has a preference toward palmitoyl-CoA and oleoyl-CoA. May be involved in absorption of dietary fat in the small intestine by catalyzing the resynthesis of triacylglycerol in enterocytes. Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG).

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

Tissue specificity. Selectively expressed in the digestive system. Highly expressed in the ileum, and at lower level in jejunum, duodenum, colon, cecum and the rectum. Not expressed in the stomach and the esophagus and trachea. Expressed at very low level in liver.

Post-translational modifications. Ubiquitinated. Ubiquitination leads to proteasomal degradation.

Pathway. Glycerolipid metabolism; triacylglycerol biosynthesis.

Similarity. Belongs to the diacylglycerol acyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86VF5-1	1	yes
Q86VF5-2	2
Q86VF5-3	3

RefSeq proteins (2): NP_001274076, NP_835470* (*=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), 9 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)
• 2-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoyl-CoA = 1,2-di-(9Z-octadecenoyl)-sn-glycerol + CoA (RHEA:37911)
• 2-(9Z-octadecenoyl)-glycerol + hexadecanoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + CoA (RHEA:38071)
• all-trans-retinol + hexadecanoyl-CoA = all-trans-retinyl hexadecanoate + CoA (RHEA:38175)
• 1,2-di-(9Z-octadecenoyl)-sn-glycerol + (9Z)-octadecenoyl-CoA = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA (RHEA:38219)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + hexadecanoyl-CoA = 1,3-dihexadecanoyl-2-(9Z-octadecenoyl)glycerol + CoA (RHEA:38299)
• 1-O-(9Z-octadecenyl)-glycerol + (9Z)-octadecenoyl-CoA = 1-O-(9Z-octadecyl)-3-(9Z-octadecenoyl)-glycerol + CoA (RHEA:55340)
• 1-O-(9Z-octadecyl)-3-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoyl-CoA = 1-O-(9Z-octadecenyl)-2,3-di-(9Z-octadecenoyl)glycerol + CoA (RHEA:55344)

UniProt features (11 total): transmembrane region 3, splice variant 3, mutagenesis site 2, chain 1, sequence conflict 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VF5-F1	93.28	0.83

Functional residue map

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

Glycosylation sites (1): 126

Mutagenesis-validated functional residues (2):

Position	Phenotype
265	reduces 60% 2-acylglycerol o-acyltransferase activity. no effect on diacylglycerol o-acyltransferase activity.
265	catalitically inactive. no 2-acylglycerol o-acyltransferase neither diacylglycerol o-acyltransferase activities.

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: 205 (showing top): GOBP_COGNITION, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_POLYOL_METABOLIC_PROCESS, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GGGTGGRR_PAX4_03, MODULE_503, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, MODULE_195, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (4): glycerol metabolic process (GO:0006071), monoacylglycerol biosynthetic process (GO:0006640), triglyceride biosynthetic process (GO:0019432), lipid metabolic process (GO:0006629)

GO Molecular Function (6): 2-acylglycerol O-acyltransferase activity (GO:0003846), diacylglycerol O-acyltransferase activity (GO:0004144), protein binding (GO:0005515), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), perinuclear endoplasmic reticulum membrane (GO:1990578), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), 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
cellular anatomical structure	3
acylglycerol biosynthetic process	2
acylglycerol O-acyltransferase activity	2
organelle membrane	2
cytoplasm	2
carbohydrate metabolic process	1
polyol metabolic process	1
monoacylglycerol metabolic process	1
triglyceride metabolic process	1
primary metabolic process	1
binding	1
catalytic activity	1
transferase activity	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
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOGAT3	DGAT1	O75907	882
MOGAT3	CANX	P27824	559
MOGAT3	MGAT1	P26572	469
MOGAT3	OR13A1	Q8NGR1	406
MOGAT3	FABP9	Q0Z7S8	403
MOGAT3	OR5P3	Q8WZ94	400
MOGAT3	OR2AE1	Q8NHA4	396
MOGAT3	ZNF835	Q9Y2P0	391
MOGAT3	CDS2	O95674	371
MOGAT3	JHY	Q6NUN7	367
MOGAT3	SLC9A4	Q6AI14	354
MOGAT3	AASDH	Q4L235	349
MOGAT3	MBOAT2	Q6ZWT7	340
MOGAT3	AGPAT3	Q9NRZ7	336
MOGAT3	ZNF37A	P17032	322
MOGAT3	FBRSL1	Q9HCM7	322

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MOGAT3	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): SERPINB8 (Affinity Capture-MS), IL36G (Affinity Capture-MS), TUBB2B (Affinity Capture-MS), SERPINB13 (Affinity Capture-MS), S100A7A (Affinity Capture-MS), GSDMA (Affinity Capture-MS), CPA4 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), ALOX12B (Affinity Capture-MS), POF1B (Affinity Capture-MS), IL37 (Affinity Capture-MS), CASP14 (Affinity Capture-MS), A2ML1 (Affinity Capture-MS), TGM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A2AIG8, A4FV98, A5PK45, A6NDV4, A6QLK4, A6QQ24, D3YWP0, F1PZV2, O09009, O15303, O35790, O55240, P04180, P35349, Q08758, Q0P5C0, Q1JPJ0, Q3T0A0, Q3T9M1, Q3U481, Q501J2, Q5E9V4, Q5SX19, Q6AYG0, Q6NUT3, Q863I4, Q86VF5, Q86VU5, Q8BVM4, Q8K297, Q8NBJ5, Q8R2H9, Q8TCT0, Q8TCT1, Q8TCT7, Q8VCE6, Q92781, Q96AZ1, Q96FB5

Diamond homologs: A1A442, K7K424, O74850, Q28C88, Q3KPP4, Q5FVP8, Q6P342, Q70VZ8, Q75BY0, Q86VF5, Q96PD7, Q9ASU1, Q9DCV3, A2ADU8, A2ADU9, A6QP72, Q08650, Q2KHS5, Q3SYC2, Q4V9F0, Q54GC1, Q58HT5, Q5M7F4, Q5M8H5, Q6E1M8, Q6E213, Q6PAZ3, Q6ZPD8, Q70VZ7, Q80W94, Q91ZV4, Q96PD6, Q96UY1, Q96UY2, Q9ZVN2, Q9LW26

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1454 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39487345:A:AG	acceptor_gain	1.0000
22:39487345:AG:A	acceptor_gain	1.0000
22:39487346:G:GA	acceptor_gain	1.0000
22:39487346:GG:G	acceptor_gain	1.0000
7:101196097:CCCA:C	acceptor_gain	1.0000
7:101196098:CCA:C	acceptor_gain	1.0000
7:101196098:CCAC:C	acceptor_gain	1.0000
7:101196099:CA:C	acceptor_gain	1.0000
7:101196099:CAC:C	acceptor_gain	1.0000
7:101196100:AC:A	acceptor_loss	1.0000
7:101196101:C:CC	acceptor_gain	1.0000
7:101196102:T:A	acceptor_loss	1.0000
7:101196186:CCCA:C	donor_gain	1.0000
7:101196386:CGCC:C	acceptor_gain	1.0000
7:101196387:GCCC:G	acceptor_loss	1.0000
7:101196388:CC:C	acceptor_gain	1.0000
7:101196388:CCCT:C	acceptor_loss	1.0000
7:101196389:CC:C	acceptor_gain	1.0000
7:101196389:CCTGG:C	acceptor_loss	1.0000
7:101196390:C:CA	acceptor_loss	1.0000
7:101196390:C:CC	acceptor_gain	1.0000
7:101196391:T:A	acceptor_loss	1.0000
7:101198187:TCA:T	donor_loss	1.0000
7:101198189:A:AC	donor_gain	1.0000
7:101198189:A:C	donor_loss	1.0000
7:101198189:AC:A	donor_gain	1.0000
7:101198190:C:CC	donor_gain	1.0000
7:101198190:CC:C	donor_gain	1.0000
7:101198361:GAGTC:G	acceptor_gain	1.0000
7:101198362:AGTC:A	acceptor_gain	1.0000

AlphaMissense

2211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101198214:G:C	F215L	0.983
7:101198214:G:T	F215L	0.983
7:101198216:A:G	F215L	0.983
7:101196003:G:C	F323L	0.972
7:101196003:G:T	F323L	0.972
7:101196005:A:G	F323L	0.972
7:101196362:A:C	F232L	0.970
7:101196362:A:T	F232L	0.970
7:101196364:A:G	F232L	0.970
7:101198215:A:G	F215S	0.949
7:101195991:C:A	K327N	0.943
7:101195991:C:G	K327N	0.943
7:101198212:A:T	V216E	0.935
7:101198215:A:C	F215C	0.928
7:101196344:A:C	F238L	0.924
7:101196344:A:T	F238L	0.924
7:101196346:A:G	F238L	0.924
7:101196287:C:A	K257N	0.916
7:101196287:C:G	K257N	0.916
7:101198717:G:C	F134L	0.912
7:101198717:G:T	F134L	0.912
7:101198719:A:G	F134L	0.912
7:101198219:C:G	G214R	0.908
7:101198705:G:C	F138L	0.906
7:101198705:G:T	F138L	0.906
7:101198707:A:G	F138L	0.906
7:101198340:G:C	S173R	0.904
7:101198340:G:T	S173R	0.904
7:101198342:T:G	S173R	0.904
7:101198663:G:C	F152L	0.894

dbSNP variants (sampled 300 via entrez): RS1000011001 (7:101194170 T>A,C), RS1000350884 (7:101201432 CT>C,CTT), RS1000527758 (7:101195408 T>C), RS1000666065 (7:101196956 A>C), RS1000805615 (7:101201133 C>A,T), RS1001381775 (7:101199719 A>G), RS1002016135 (7:101196691 A>G), RS1002247243 (7:101192939 G>A,T), RS1002527958 (7:101192650 T>G), RS1002581262 (7:101194053 G>A), RS1002675830 (7:101199382 A>C), RS1002748994 (7:101198088 T>A,C), RS1003380919 (7:101196779 G>A), RS1003612769 (7:101197260 G>T), RS1003962558 (7:101200594 C>A)

Disease associations

OMIM: gene MIM:610184 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012353_34	Serum metabolite concentrations in chronic kidney disease	6.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465325 (SINGLE PROTEIN)

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

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	2
Tetrachlorodibenzodioxin	increases expression	2
dicrotophos	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	decreases methylation, affects cotreatment	1
Microplastics	increases abundance, increases expression	1
Formaldehyde	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polyethylene Terephthalates	increases expression, increases abundance	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Sodium Selenite	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5323319	Binding	Inhibition of human MGAT3	Discovery of novel pyridinones as MGAT2 inhibitors for the treatment of metabolic disorders. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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