MGAT1

Summary

MGAT1 (alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase, HGNC:7044) is a protein-coding gene on chromosome 5q35.3, encoding Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (P26572). Initiates complex N-linked carbohydrate formation. It is a selective cancer dependency (DepMap: 23.6% of cell lines).

There are believed to be over 100 different glycosyltransferases involved in the synthesis of protein-bound and lipid-bound oligosaccharides. UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I is a medial-Golgi enzyme essential for the synthesis of hybrid and complex N-glycans. The protein, encoded by a single exon, shows typical features of a type II transmembrane protein. The protein is believed to be essential for normal embryogenesis. Several variants encoding the same protein have been found for this gene.

Source: NCBI Gene 4245 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 93 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 23.6% of screened cell lines
• MANE Select transcript: NM_002406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7044
Approved symbol	MGAT1
Name	alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	GNT-1, GLCNAC-TI, GnTI
Ensembl gene	ENSG00000131446
Ensembl biotype	protein_coding
OMIM	160995
Entrez	4245

Gene structure

Transcript identifiers

Ensembl transcripts: 60 — 49 protein_coding, 11 protein_coding_CDS_not_defined

ENST00000307826, ENST00000333055, ENST00000393340, ENST00000427865, ENST00000446023, ENST00000502678, ENST00000504385, ENST00000504671, ENST00000505682, ENST00000506033, ENST00000506269, ENST00000506708, ENST00000506889, ENST00000507384, ENST00000508090, ENST00000508702, ENST00000510341, ENST00000510962, ENST00000512080, ENST00000512695, ENST00000513149, ENST00000513431, ENST00000514283, ENST00000514438, ENST00000514760, ENST00000896404, ENST00000896405, ENST00000896406, ENST00000896407, ENST00000896408, ENST00000896409, ENST00000896410, ENST00000896411, ENST00000896412, ENST00000896413, ENST00000896414, ENST00000896415, ENST00000896416, ENST00000916776, ENST00000916777, ENST00000916778, ENST00000946446, ENST00000946447, ENST00000946448, ENST00000946449, ENST00000946450, ENST00000946451, ENST00000946452, ENST00000946453, ENST00000946454, ENST00000946455, ENST00000946456, ENST00000946457, ENST00000946458, ENST00000946459, ENST00000946460, ENST00000946461, ENST00000946462, ENST00000946463, ENST00000946464

RefSeq mRNA: 23 — MANE Select: NM_002406 NM_001114617, NM_001114618, NM_001114619, NM_001114620, NM_001364377, NM_001364379, NM_001364380, NM_001364381, NM_001364382, NM_001364383, NM_001364384, NM_001364385, NM_001364386, NM_001364387, NM_001364388, NM_001364389, NM_001364390, NM_001364391, NM_001364392, NM_001364393, NM_001364394, NM_001364395, NM_002406

CCDS: CCDS4458

Canonical transcript exons

ENST00000307826 — 2 exons

Exon	Start	End
ENSE00001514922	180802680	180802806
ENSE00001979267	180784780	180793097

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.6584 / max 652.9826, expressed in 1825 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65320	22.0964	1800
65322	17.2002	1004
65321	4.1775	1564
65334	3.0572	290
65327	2.7648	1503
65326	2.7500	1328
65331	1.3738	227
65330	0.7806	406
65324	0.5889	187
65329	0.5873	363

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.35	gold quality
leukocyte	CL:0000738	98.11	gold quality
mononuclear cell	CL:0000842	98.11	gold quality
granulocyte	CL:0000094	98.04	gold quality
omental fat pad	UBERON:0010414	98.01	gold quality
peritoneum	UBERON:0002358	97.98	gold quality
right lung	UBERON:0002167	97.94	gold quality
mucosa of stomach	UBERON:0001199	97.91	gold quality
upper lobe of left lung	UBERON:0008952	97.80	gold quality
apex of heart	UBERON:0002098	97.68	gold quality
right lobe of thyroid gland	UBERON:0001119	97.62	gold quality
left uterine tube	UBERON:0001303	97.59	gold quality
lower esophagus mucosa	UBERON:0035834	97.57	gold quality
spleen	UBERON:0002106	97.53	gold quality
left lobe of thyroid gland	UBERON:0001120	97.52	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.42	gold quality
upper lobe of lung	UBERON:0008948	97.39	gold quality
body of pancreas	UBERON:0001150	97.37	gold quality
right coronary artery	UBERON:0001625	97.05	gold quality
stromal cell of endometrium	CL:0002255	96.99	gold quality
thyroid gland	UBERON:0002046	96.91	gold quality
thoracic aorta	UBERON:0001515	96.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.88	gold quality
tibial nerve	UBERON:0001323	96.87	gold quality
ascending aorta	UBERON:0001496	96.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.86	gold quality
right ovary	UBERON:0002118	96.85	gold quality
lower esophagus	UBERON:0013473	96.85	gold quality
left coronary artery	UBERON:0001626	96.84	gold quality
endocervix	UBERON:0000458	96.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	69.35
E-MTAB-5061	no	3.49
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG, SP1

miRNA regulators (miRDB)

45 targeting MGAT1, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-637	97.91	64.05	1517

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• Findings indicated that cysteine 121 has a structural role in maintaining active site geometry of hGnT1, rather than a catalytic role, and illustrates for the first time the potential utility of E. coli as an expression system for hGnT1. (PMID:17716624)
• Activity of HuGnTI in plants is limited by a combination of reduced protein stability, alternative protein targeting and possibly to some extend to lower enzymatic performance of the catalytic domain in the plant biochemical environment. (PMID:19826906)
• The analysis enabled us to identify a new candidate gene, MGAT1, associated with weight in women. (PMID:19851299)
• Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Delta desaturase indices, variables previously shown to correlate with obesity. (PMID:21304485)
• analysis of suppression of cancer progression by MGAT1 shRNA knockdown (PMID:22957033)
• The IL2RA and IL7RA variants had univariate association in MS and T1D, whereas the MGAT1 and CTLA-4 variants associated with only MS or T1D, respectively. (PMID:24572742)
• UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases (Mgats). (PMID:25944901)
• The authors show here that the luminal domain of GnT1IP-L contains its MGAT1 inhibitory activity. (PMID:26371870)
• MGAT1 is downregulated in peripheral blood mononuclear cells of galactosaemia patients. (PMID:26733289)
• The presence of the rs4285184 polymorphism of the MGAT1 gene increased the risk for developing body fat associated with obesity in the Mexican population. (PMID:27871764)
• In this study we showed that the activation of Wnt/beta-catenin pathway culminates in the upregulation of MGAT1 enzyme both at transcriptional and post-transcriptional levels. We also showed that overexpression of the beta-catenin gene (CTNNB1) increased the promoter activity of MGAT1. (PMID:29310626)
• MGAT1 activity may play a role in regulating basal adipocyte FFA retention (PMID:29853530)
• MGAT1 promotes complex N-glycosylation of glucose transporter 1 (Glut1) and increases Glut1 protein levels. In summary, our findings indicate that MGAT1 is highly expressed in glioblastoma and promotes glioma cells at least partly through upregulation of Glut1 protein. (PMID:31494931)
• Point mutations that inactivate MGAT4D-L, an inhibitor of MGAT1 and complex N-glycan synthesis. (PMID:32763972)
• Elucidating the multifaceted role of MGAT1 in hepatocellular carcinoma: integrative single-cell and spatial transcriptomics reveal novel therapeutic insights. (PMID:39081317)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mgat1a	ENSDARG00000012407
danio_rerio	mgat1b	ENSDARG00000036065
mus_musculus	Mgat1	ENSMUSG00000020346
rattus_norvegicus	Mgat1	ENSRNOG00000068826
drosophila_melanogaster	Mgat1	FBGN0034521

Paralogs (1): POMGNT1 (ENSG00000085998)

Protein

Protein identifiers

Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase — P26572 (reviewed: P26572)

Alternative names: N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase I

All UniProt accessions (10): D6R9U2, D6RA48, D6RAK2, D6RB69, D6RBS3, D6RD15, D6RF69, D6RHZ8, D6RIS2, P26572

UniProt curated annotations — full annotation on UniProt →

Function. Initiates complex N-linked carbohydrate formation. Essential for the conversion of high-mannose to hybrid and complex N-glycans.

Subunit / interactions. Interacts with MGAT4D. Interacts with BRI3 (isoforms 1 and 2); the interaction with isoform 2 is weaker than with isoform 1.

Subcellular location. Golgi apparatus membrane. Cytoplasm. Perinuclear region.

Cofactor. The cofactor is mostly bound to the substrate.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 13 family.

RefSeq proteins (23): NP_001108089, NP_001108090, NP_001108091, NP_001108092, NP_001351306, NP_001351308, NP_001351309, NP_001351310, NP_001351311, NP_001351312, NP_001351313, NP_001351314, NP_001351315, NP_001351316, NP_001351317, NP_001351318, NP_001351319, NP_001351320, NP_001351321, NP_001351322, NP_001351323, NP_001351324, NP_002397* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004139	Glyco_trans_13	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR052261	Glycosyltransferase_13	Family

Pfam: PF03071

Enzyme classification (BRENDA):

• EC 2.4.1.101 — alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (BRENDA: 22 organisms, 109 substrates, 34 inhibitors, 52 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

32 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-N-ACETYL-D-GLUCOSAMINE	0.036–7.56	7
MAN5GLCNAC2	0.26–5.43	3
ALPHA-D-MANNOSYL-1,3-(ALPHA-D-MANNOSYL-1,6)-ALPH	0.25–0.47	2
ALPHA-D-MANNOSYL-1,3-(ALPHA-D-MANNOSYL-1,6)-BETA	0.0384–0.2	2
ALPHA-D-MANNOSYL-1,6-(ALPHA-D-MANNOSYL-1,3)-ALPH	0.39–0.45	2
MANALPHA6(MANALPHA3)MAN-O-BETA4-N-ACETYL-D-GLUCO	2.7–4.5	2
OVALBUMIN	0.44–4.5	2
OVALBUMIN GLYCOPEPTIDE V	0.12–0.33	2
2-DEOXY-MANALPHA6(MANALPHA3)MAN-BETA-OCTYL	0.6	1
3-O-(4,4-AZOPENTYL)-MANALPHA6(MANALPHA3)MAN-BETA	1.2	1
3-O-(4,5-EPOXYPENTYL)-MANALPHA6(MANALPHA3)MAN-BE	1.8	1
3-O-(5-IODOACETAMIDOPENTYL)-MANALPHA6(MANALPHA3)	1.4	1
3-O-PENTYL-MANALPHA6(MANALPHA3)MAN-BETA-OCTYL	3.5	1
4-O-METHYL-MANALPHA6(MANALPHA3)MAN-BETA-OCTYL	0.9	1
6-O-METHYL-MANALPHA6(MANALPHA3)MAN-BETA-OCTYL	0.3	1

Catalyzed reactions (Rhea), 2 shown:

• N(4)-(alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein] (N-glucan mannose isomer 5A1,2) + UDP-N-acetyl-alpha-D-glucosamine = N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:11456)
• an N(4)-{alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:84123)

UniProt features (16 total): binding site 6, topological domain 2, disulfide bond 2, sequence variant 2, chain 1, sequence conflict 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26572-F1	89.27	0.74

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 (1): 289 (proton acceptor)

Ligand- & substrate-binding residues (6): 320; 115; 142; 188; 210; 211

Disulfide bonds (2): 113–143, 237–303

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-964739	N-glycan trimming and elongation in the cis-Golgi
R-HSA-9683686	Maturation of spike protein
R-HSA-9694548	Maturation of spike protein
R-HSA-1643685	Disease
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9683701	Translation of Structural Proteins
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9694635	Translation of Structural Proteins
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 265 (showing top): MORF_RAGE, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, AAAYRNCTG_UNKNOWN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT

GO Biological Process (6): in utero embryonic development (GO:0001701), protein N-linked glycosylation (GO:0006487), obsolete protein N-linked glycosylation via asparagine (GO:0018279), viral protein processing (GO:0019082), obsolete UDP-N-acetylglucosamine catabolic process (GO:0006049), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (7): alpha-1,3-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activity (GO:0003827), acetylglucosaminyltransferase activity (GO:0008375), manganese ion binding (GO:0030145), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (8): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), extracellular vesicle (GO:1903561), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
SARS-CoV Infections	2
Transport to the Golgi and subsequent modification	1
Translation of Structural Proteins	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1
Viral Infection Pathways	1
SARS-CoV-1 Infection	1
Late SARS-CoV-2 Infection Events	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
bounding membrane of organelle	2
cytoplasm	2
chordate embryonic development	1
glycoprotein biosynthetic process	1
viral process	1
viral gene expression	1
acetylglucosaminyltransferase activity	1
catalytic activity, acting on a glycoprotein	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
transferase activity	1
cation binding	1
Golgi apparatus	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum-Golgi intermediate compartment	1
extracellular vesicle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MGAT1	MGAT2	Q10469	943
MGAT1	ADGRL2	O95490	925
MGAT1	MGAT3	Q09327	880
MGAT1	MGAT5	Q09328	867
MGAT1	DGAT1	O75907	790
MGAT1	MAN2A1	Q16706	731
MGAT1	MAN2A2	P49641	712
MGAT1	LARGE1	O95461	663
MGAT1	MGAT4D	A6NG13	631
MGAT1	FUT8	Q9BYC5	616
MGAT1	MGAT4B	Q9UQ53	600
MGAT1	MAN1A1	P33908	591
MGAT1	GCNT2	Q8N0V5	584
MGAT1	ALG3	Q92685	577
MGAT1	MGAT4A	Q9UM21	576

IntAct

60 interactions, top by confidence:

A	B	Type	Score
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
BRI3	MGAT1	psi-mi:“MI:0915”(physical association)	0.540
BRI3	MGAT1	psi-mi:“MI:0403”(colocalization)	0.540
MGAT1	BRI3	psi-mi:“MI:0915”(physical association)	0.540
RELL1	TCAF2	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
HFE	ADAM10	psi-mi:“MI:0914”(association)	0.530
TMEM106A	B4GALT3	psi-mi:“MI:0914”(association)	0.530
	MGAT1	psi-mi:“MI:0915”(physical association)	0.400
MGAT1	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
MGAT1	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
Anapc13	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Mus81	KIF1B	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ADPGK	TOR1B	psi-mi:“MI:0914”(association)	0.350
FUT8	ITGAV	psi-mi:“MI:0914”(association)	0.350
	PLOD2	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TNFSF18	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), MGAT1 (Synthetic Rescue), MGAT1 (Positive Genetic)

ESM2 similar proteins: A0JPH3, A1YGR5, A3KGW5, A5PMF6, A7MB73, O00469, O14638, O43909, O77588, P06802, P15396, P24802, P26572, P27115, P27808, P50127, P79948, P79949, P97675, Q02809, Q09325, Q32NJ7, Q3L7M0, Q5IGR6, Q5R5M5, Q5R9N3, Q5T4B2, Q5U309, Q5U483, Q5XPT3, Q5ZLK4, Q63321, Q66PG1, Q66PG2, Q66PG4, Q6DYE8, Q6NVG7, Q6P7A1, Q6P9A2, Q6PA90

Diamond homologs: P26572, P27115, P27808, Q09325, Q11068, Q5EAB6, Q5RCB9, Q5XIN7, Q8WZA1, Q91X88, Q9XGM8, P97805, Q96BQ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	5
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010198 (5:180788111 A>G), RS1000025361 (5:180813524 G>A), RS1000186146 (5:180802370 C>T), RS1000218119 (5:180806143 G>A,T), RS1000249367 (5:180806409 A>G), RS1000636384 (5:180789707 A>C), RS1000656654 (5:180796465 G>A,T), RS1000689683 (5:180784977 G>T), RS1000708636 (5:180796349 G>A), RS1000744758 (5:180785270 G>A), RS1000788106 (5:180801079 G>T), RS1000828057 (5:180810947 G>C), RS1000890641 (5:180815057 C>T), RS1000958055 (5:180791142 C>T), RS1000983923 (5:180787027 G>A)

Disease associations

OMIM: gene MIM:160995 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000337_8	Quantitative traits	5.000000e-06
GCST000511_5	Weight	7.000000e-08
GCST001859_1	Thiazide-induced adverse metabolic effects in hypertensive patients	8.000000e-06
GCST010241_292	Apolipoprotein A1 levels	8.000000e-09
GCST011418_1	HDL cholesterol levels	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004338	body weight
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2375207 (SINGLE PROTEIN)

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 8 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.50	IC50	31.62	nM	CHEMBL2376329
7.30	IC50	50.12	nM	CHEMBL2376325
7.20	IC50	63.1	nM	CHEMBL2376321
6.80	IC50	158.5	nM	CHEMBL2376327
6.40	IC50	398.1	nM	CHEMBL2376312
6.30	IC50	501.2	nM	CHEMBL2376322

PubChem BioAssay actives

6 with measured affinity, of 13 total; 6 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
3-ethyl-N-(4-methoxyphenyl)-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745093: Inhibition of human recombinant MGAT1 expressed in insect cell membrane using 2-oleyl-sn-glycerol and [14C]-oleyl-coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting analysis	ic50	0.0316	uM
N-(4-chlorophenyl)-3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745093: Inhibition of human recombinant MGAT1 expressed in insect cell membrane using 2-oleyl-sn-glycerol and [14C]-oleyl-coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting analysis	ic50	0.0501	uM
(3S)-N-[4-(difluoromethoxy)phenyl]-3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745093: Inhibition of human recombinant MGAT1 expressed in insect cell membrane using 2-oleyl-sn-glycerol and [14C]-oleyl-coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting analysis	ic50	0.0631	uM
N-(2-chlorophenyl)-3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745093: Inhibition of human recombinant MGAT1 expressed in insect cell membrane using 2-oleyl-sn-glycerol and [14C]-oleyl-coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting analysis	ic50	0.1585	uM
N-(4-chlorophenyl)-3-ethyl-1,3-dimethyl-2,5-dioxo-4H-1,4-benzodiazepine-7-sulfonamide	745093: Inhibition of human recombinant MGAT1 expressed in insect cell membrane using 2-oleyl-sn-glycerol and [14C]-oleyl-coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting analysis	ic50	0.3981	uM
3-ethyl-3-methyl-2,5-dioxo-N-phenyl-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745093: Inhibition of human recombinant MGAT1 expressed in insect cell membrane using 2-oleyl-sn-glycerol and [14C]-oleyl-coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting analysis	ic50	0.5012	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases abundance, affects cotreatment, affects methylation, decreases methylation	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	increases abundance, affects cotreatment, increases oxidation	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Smoke	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
cupric chloride	increases expression	1
beta-methylcholine	affects expression	1
bisphenol S	affects expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Rotenone	increases expression	1
Selenium	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2378968	Binding	Inhibition of human recombinant MGAT1 expressed in insect cell membrane using 2-oleyl-sn-glycerol and [14C]-oleyl-coenzyme A as substrate after 10 to 15 mins by liquid scintillation counting analysis	Identification and design of a novel series of MGAT2 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 3 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_RN04	PDIS-1	Transformed cell line	Female
CVCL_RN05	PDIS-12	Transformed cell line	Female
CVCL_SY24	HAP1 MGAT1 (-) 1	Cancer cell line	Male
CVCL_XQ51	HAP1 MGAT1 (-) 2	Cancer cell line	Male
CVCL_XQ52	HAP1 MGAT1 (-) 3	Cancer cell line	Male
CVCL_Z366	SfSWT-1	Spontaneously immortalized cell line	Female
CVCL_Z367	SfSWT-3	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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