MGAT3

Summary

MGAT3 (beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase, HGNC:7046) is a protein-coding gene on chromosome 22q13.1, encoding Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (Q09327). It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides.

There are believed to be over 100 different glycosyltransferases involved in the synthesis of protein-bound and lipid-bound oligosaccharides. The enzyme encoded by this gene transfers a GlcNAc residue to the beta-linked mannose of the trimannosyl core of N-linked oligosaccharides and produces a bisecting GlcNAc. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 4248 — RefSeq curated summary.

At a glance

• GWAS associations: 40
• Clinical variants (ClinVar): 69 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7046
Approved symbol	MGAT3
Name	beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	GNT-III
Ensembl gene	ENSG00000128268
Ensembl biotype	protein_coding
OMIM	604621
Entrez	4248

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000341184, ENST00000418314, ENST00000429402, ENST00000855331, ENST00000855332, ENST00000855333, ENST00000855334, ENST00000855335, ENST00000920231, ENST00000920232

RefSeq mRNA: 2 — MANE Select: NM_002409 NM_001098270, NM_002409

CCDS: CCDS13994

Canonical transcript exons

ENST00000341184 — 2 exons

Exon	Start	End
ENSE00001048223	39457012	39457557
ENSE00001525937	39487347	39492194

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 92.19.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6764 / max 69.2828, expressed in 639 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192351	1.5021	399
192353	0.8377	342
192352	0.5953	326
192357	0.3738	96
192350	0.1850	81
192358	0.0918	39
192349	0.0906	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	92.19	gold quality
cerebellar hemisphere	UBERON:0002245	91.57	gold quality
cerebellar cortex	UBERON:0002129	91.48	gold quality
right frontal lobe	UBERON:0002810	91.41	gold quality
cortical plate	UBERON:0005343	90.68	gold quality
cerebellum	UBERON:0002037	90.18	gold quality
prefrontal cortex	UBERON:0000451	89.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.24	gold quality
olfactory bulb	UBERON:0002264	88.81	silver quality
nucleus accumbens	UBERON:0001882	88.48	gold quality
frontal cortex	UBERON:0001870	88.46	gold quality
cingulate cortex	UBERON:0003027	88.44	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.26	gold quality
amygdala	UBERON:0001876	88.22	gold quality
anterior cingulate cortex	UBERON:0009835	88.16	gold quality
neocortex	UBERON:0001950	88.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.79	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.21	gold quality
cerebral cortex	UBERON:0000956	87.19	gold quality
putamen	UBERON:0001874	87.17	gold quality
telencephalon	UBERON:0001893	86.99	gold quality
Ammon’s horn	UBERON:0001954	86.47	gold quality
inferior olivary complex	UBERON:0002127	86.41	gold quality
type B pancreatic cell	CL:0000169	86.37	gold quality
caudate nucleus	UBERON:0001873	86.30	gold quality
hypothalamus	UBERON:0001898	86.21	gold quality
orbitofrontal cortex	UBERON:0004167	85.99	gold quality
gluteal muscle	UBERON:0002000	85.94	gold quality
pons	UBERON:0000988	85.90	gold quality
temporal lobe	UBERON:0001871	85.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting MGAT3, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4503	99.85	71.45	1869

Literature-anchored findings (GeneRIF, showing 23)

• down-regulation of hydrogen peroxide-induced PKC delta activation in cells transfected with this enzyme (PMID:12427758)
• beta1,4-N-acetylglucosaminyltransferase III inhibits the function of alpha5beta1 integrin (PMID:14998999)
• An N-glycosylation site on the beta-propeller domain of the integrin alpha5 subunit plays key roles in both its function and site-specific modification by beta1,4-N-acetylglucosaminyltransferase III. (PMID:19276077)
• MGAT3 and MGAT5 competitively modified E-cadherin N-glycans. (PMID:19403558)
• upregulation of GnT-III in AD brains may represent an adaptive response to protect them from additional beta-amyloid production (PMID:19776078)
• the modulation of glycosyltransferases MGAT3 and MGAT5 by synthetic N-acetyl-D-glucosamine-calix[4]arene correlated with the improvement of NK cell effector functions and the augmentation of tumor cells sensitivity to NK cell-mediated cytotoxicity. (PMID:20089585)
• MGAT3 mRNA biomarker may characterize subgroups of Alzheimer’s disease patients with different disease progression. (PMID:21368380)
• Roles of N-acetylglucosaminyltransferase III in epithelial-to-mesenchymal transition induced by transforming growth factor beta1 (TGF-beta1) in epithelial cell lines (PMID:22451656)
• GnT-III determines E-cadherin-mediated tumor suppression, and GnT-V regulates E-cadherin-mediated tumor invasion. (PMID:23671930)
• functional characterization of N-acetylglucosaminyltransferases III and V in human melanoma cells (PMID:24726881)
• HS5 cells had significantly enhanced levels of bisecting N-glycans (catalyzed by MGAT3 whereas HS27a cells had enhanced levels of Galbeta1,4GlcNAc. (PMID:25936519)
• MGAT3 protein and gene expression in in uveal and cutaneous melanoma cells (PMID:26098720)
• Mgat3 plays an important role in early spontaneous miscarriage in humans. (PMID:26109616)
• High expression of alpha2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. (PMID:26801611)
• Core-fucosylated tetra-antennary structures were decreased in quantity likely as a result of hypomethylated MGAT3 gene promoter followed by increased expression of this gene (PMID:27073020)
• MGAT3 expressed in cells stimulates lipid droplet growth. These findings provide additional evidence that MGAT3 likely functions as a triacylglycerol synthase in cells. (PMID:27184406)
• Novel insights into the epigenetic regulation of MGAT3/bisecting GlcNAc and demonstrate the importance of N-glycosylation in cancer progression. (PMID:27429195)
• Data suggest that GNT-III expression regulates levels/activation of the heavily glycosylated Notch receptor involved in normal and malignant cell development; suppression of GNT-III in epithelial ovarian carcinoma cell lines results in down-regulation of Notch signaling that is more potent than pharmacologic blockage of Notch activation. (PMID:28842505)
• The expression of GnT-III in placenta suggests a role for GnT-III in the regulation of tropho- blast behavior. And decreased expression of GnT-III is associated with oxidative stress in preeclamptic pla- centas and, thus, may be involved in the pathogenesis of preeclampsia. (PMID:29466889)
• Study found that N-Acetylglucosaminyltransferase III (GnT-III) is expressed in trophoblasts during normal human pregnancy and is involved in regulating trophoblast function. (PMID:29642803)
• Results strongly indicate that the MGAT3 and BACH2 genes play an important role in IBD pathogenesis and suggest a possible disease pathway mediated by the pro-inflammatory properties of IgG antibodies acquired by alterations in Fc glycosylation. (PMID:29991969)
• Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk. (PMID:33200553)
• Suppression of MGAT3 expression and the epithelial-mesenchymal transition of lung cancer cells by miR-188-5p. (PMID:35166206)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mgat3b	ENSDARG00000036619
danio_rerio	mgat3a	ENSDARG00000038069
mus_musculus	Mgat3	ENSMUSG00000042428
rattus_norvegicus	Mgat3	ENSRNOG00000017434
drosophila_melanogaster	Mgat3	FBGN0051849

Protein

Protein identifiers

Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase — Q09327 (reviewed: Q09327)

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

All UniProt accessions (3): Q09327, B0QY92, B0QY93

UniProt curated annotations — full annotation on UniProt →

Function. It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked sugar chains, called bisecting N-acetylglucosamine (GlcNAc). It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. The addition of this bisecting GlcNAc residue alters not only the composition, but also the conformation of the N-glycan. The introduction of the bisecting GlcNAc residue results in the suppression of further processing and elongation of N-glycans, precluding the formation of beta-1,6 GlcNAc branching, catalyzed by MGAT5 since it is unable to use the bisected oligosaccharide as a substrate. Addition of bisecting N-acetylglucosamine to CDH1/E-cadherin modulates CDH1 cell membrane location. Inhibits NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc- formation which modulates sialylation levels and plays a role in cell migration regulation. In brain, addition of bisecting N-acetylglucosamine to BACE1 blocks its lysosomal targeting in response to oxidative stress and further degradation which increases its location to early endosome and the APP cleavage. Adds bisecting GlcNAc residue to complex-type N-linked-glycans attached on fragment crystallizable (Fc) of IgGs. Readily converts fucosylated and non-fucosylated core glycoforms with terminal GlcNAcs on both antennae. Prior galactosylation of GlcNAc on the alpha(1->3) Man branch prevents N-glycan bisection, whereas galactosylation of GlcNAc on the alpha(1->6) Man branch is permissive.

Subunit / interactions. Interacts with MGAT4D.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Induction. Expression is up-regulated by CDH1/E-cadherin-mediated cell-cell interaction.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 17 family.

RefSeq proteins (2): NP_001091740, NP_002400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006813	Glyco_trans_17	Family

Pfam: PF04724

Enzyme classification (BRENDA):

• EC 2.4.1.144 — beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (BRENDA: 8 organisms, 67 substrates, 22 inhibitors, 18 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PYRIDYLAMINATED ACCEPTOR SUBSTRATE	0.021–3.4	9
UDP-N-ACETYL-D-GLUCOSAMINE	0.42–6.8	5
(N-ACETYL-BETA-D-GLUCOSAMINYL-1,2-ALPHA-D-MANNOS	0.23	1
UDP-D-GLUCOSE	1	1
UDP-N-ACETYL-D-GALACTOSAMINE	3.6	1

Catalyzed reactions (Rhea), 3 shown:

• N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-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 = N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:15509)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-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)-[beta-D-GlcNAc-(1->4)]-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:83967)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-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)-[beta-D-GlcNAc-(1->4)]-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:85375)

UniProt features (11 total): glycosylation site 4, topological domain 2, region of interest 2, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q09327-F1	79.68	0.64

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 (4): 141, 241, 259, 397

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-975574	Reactions specific to the hybrid N-glycan synthesis pathway
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-975576	N-glycan antennae elongation in the medial/trans-Golgi

MSigDB gene sets: 156 (showing top): GOBP_COGNITION, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, 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, MODULE_195, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (10): N-acetylglucosamine metabolic process (GO:0006044), protein N-linked glycosylation (GO:0006487), intracellular protein localization (GO:0008104), regulation of cell migration (GO:0030334), cellular response to oxidative stress (GO:0034599), amyloid-beta metabolic process (GO:0050435), cognition (GO:0050890), positive regulation of protein localization to early endosome (GO:1902966), negative regulation of lysosomal protein catabolic process (GO:1905166), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (4): beta-1,4-mannosylglycoprotein 4-beta-N-acetylglucosaminyltransferase activity (GO:0003830), glycosyltransferase activity (GO:0016757), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (3): Golgi membrane (GO:0000139), membrane (GO:0016020), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
N-glycan antennae elongation in the medial/trans-Golgi	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1
Transport to the Golgi and subsequent modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
amino sugar metabolic process	1
glycoprotein biosynthetic process	1
macromolecule localization	1
cell migration	1
regulation of cell motility	1
response to oxidative stress	1
cellular response to chemical stress	1
metabolic process	1
nervous system process	1
protein localization to early endosome	1
regulation of protein localization to early endosome	1
positive regulation of protein localization to endosome	1
negative regulation of protein catabolic process in the vacuole	1
lysosomal protein catabolic process	1
regulation of lysosomal protein catabolic process	1
acetylglucosaminyltransferase activity	1
catalytic activity, acting on a glycoprotein	1
transferase activity	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MGAT3	MGAT5	Q09328	950
MGAT3	MGAT1	P26572	880
MGAT3	MGAT5B	Q3V5L5	804
MGAT3	FUT8	Q9BYC5	720
MGAT3	MGAT2	Q10469	716
MGAT3	MGAT4B	Q9UQ53	709
MGAT3	MGAT4A	Q9UM21	695
MGAT3	CDH1	P12830	634
MGAT3	ST6GAL1	P15907	604
MGAT3	GCNT2	Q8N0V5	552
MGAT3	CSDC2	Q9Y534	546
MGAT3	FXYD5	Q96DB9	514
MGAT3	MAN2A1	Q16706	506
MGAT3	NECTIN1	Q15223	463
MGAT3	B4GALT1	P15291	447

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MGAT3	UBAC1	psi-mi:“MI:0915”(physical association)	0.560
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
UBAC1	MGAT3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): UBAC1 (Two-hybrid), MGAT3 (Affinity Capture-RNA), MGAT3 (Affinity Capture-MS)

ESM2 similar proteins: A0PJZ3, A2XFP3, A2XFT5, A2XFT6, B8AIZ4, C7J0P3, O04536, O48684, O88829, P08037, P15291, P15535, Q02527, Q09327, Q0V7R1, Q0WV13, Q10470, Q10MK2, Q10MQ0, Q16842, Q3UHH8, Q4G148, Q5CAZ6, Q5K027, Q5MJS3, Q5SP46, Q5ZKI6, Q68G12, Q6DE37, Q6GX83, Q6H765, Q6KB58, Q701R2, Q70D51, Q810K9, Q8CID3, Q8GWT1, Q8IXL6, Q8RXE1, Q92184

Diamond homologs: Q02527, Q09327, Q10470

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3462 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39487864:T:A	C173S	1.000
22:39487865:G:C	C173S	1.000
22:39487878:G:C	W177C	1.000
22:39487878:G:T	W177C	1.000
22:39487892:G:A	C182Y	1.000
22:39488205:G:C	W286C	1.000
22:39488205:G:T	W286C	1.000
22:39488297:A:T	D317V	1.000
22:39488303:A:T	D319V	1.000
22:39488563:T:A	W406R	1.000
22:39488563:T:C	W406R	1.000
22:39488596:T:A	W417R	1.000
22:39488596:T:C	W417R	1.000
22:39488598:G:C	W417C	1.000
22:39488598:G:T	W417C	1.000
22:39488599:C:G	H418D	1.000
22:39488602:T:C	C419R	1.000
22:39488603:G:A	C419Y	1.000
22:39488604:C:G	C419W	1.000
22:39488608:T:A	W421R	1.000
22:39488608:T:C	W421R	1.000
22:39488610:G:C	W421C	1.000
22:39488610:G:T	W421C	1.000
22:39488611:T:C	C422R	1.000
22:39488612:G:A	C422Y	1.000
22:39488613:C:G	C422W	1.000
22:39488640:G:C	K431N	1.000
22:39488640:G:T	K431N	1.000
22:39488642:T:C	L432P	1.000
22:39488647:T:C	S434P	1.000

dbSNP variants (sampled 300 via entrez): RS1000025815 (22:39467388 C>G,T), RS1000112034 (22:39481834 T>A), RS1000189159 (22:39471300 A>G), RS1000242146 (22:39476852 A>T), RS1000274613 (22:39479737 A>G), RS1000274624 (22:39481663 G>A), RS1000279764 (22:39465105 C>A), RS1000319148 (22:39466496 C>T), RS1000415508 (22:39466325 C>T), RS1000491850 (22:39460007 A>C,G), RS1000576520 (22:39478020 G>A,C), RS1000622388 (22:39466469 T>C), RS1000645575 (22:39467524 C>A,T), RS1000758906 (22:39472735 C>A), RS1000775360 (22:39461179 C>G)

Disease associations

OMIM: gene MIM:604621 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST001848_106	IgG glycosylation	2.000000e-06
GCST001848_127	IgG glycosylation	6.000000e-10
GCST001848_132	IgG glycosylation	2.000000e-15
GCST001848_216	IgG glycosylation	6.000000e-16
GCST001848_290	IgG glycosylation	5.000000e-10
GCST001848_311	IgG glycosylation	3.000000e-08
GCST001848_342	IgG glycosylation	2.000000e-10
GCST001848_399	IgG glycosylation	3.000000e-13
GCST001848_428	IgG glycosylation	3.000000e-09
GCST001848_444	IgG glycosylation	2.000000e-10
GCST001848_460	IgG glycosylation	1.000000e-10
GCST001848_477	IgG glycosylation	3.000000e-09
GCST001848_563	IgG glycosylation	1.000000e-24
GCST001848_592	IgG glycosylation	1.000000e-16
GCST001848_632	IgG glycosylation	9.000000e-24
GCST001848_74	IgG glycosylation	9.000000e-06
GCST001849_3	IgG glycosylation	3.000000e-08
GCST001849_5	IgG glycosylation	2.000000e-10
GCST001849_6	IgG glycosylation	9.000000e-06
GCST003262_253	Post bronchodilator FEV1	1.000000e-06
GCST003262_255	Post bronchodilator FEV1	3.000000e-06
GCST003262_256	Post bronchodilator FEV1	2.000000e-06
GCST003262_258	Post bronchodilator FEV1	1.000000e-07
GCST004924_5	IgG monogalactosylation phenotypes (multivariate analysis)	1.000000e-06
GCST004925_5	IgG N-glycosylation phenotypes (multivariate analysis)	3.000000e-19
GCST004926_5	IgG digalactosylation phenotypes (multivariate analysis)	3.000000e-13
GCST004927_4	IgG galactosylation phenotypes (multivariate analysis)	2.000000e-14
GCST004928_3	IgG bisecting N-acetyl glucosamine phenotypes (multivariate analysis)	4.000000e-10
GCST004929_4	IgG fucosylation phenotypes (multivariate analysis)	1.000000e-20
GCST004930_4	IgG sialylation phenotypes (multivariate analysis)	1.000000e-13

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0004314	forced expiratory volume
EFO:0008423	IgG monogalactosylation measurement
EFO:0008424	IgG digalactosylation measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008426	IgG bisecting N-acetyl glucosamine measurement
EFO:0008427	IgG fucosylation measurement
EFO:0008428	IgG sialylation measurement
EFO:0008429	IgG disialylation measurement
EFO:0004337	intelligence
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2375206 (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)

ChEMBL bioactivities

30 potent at pChembl≥5 of 31 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	IC50	6	nM	CHEMBL3613706
8.22	IC50	6	nM	CHEMBL3613707
8.20	IC50	6.31	nM	CHEMBL3613706
8.20	IC50	6.31	nM	CHEMBL3613707
7.30	IC50	50.12	nM	CHEMBL2376303
7.20	IC50	63	nM	CHEMBL3613712
7.20	IC50	63.1	nM	CHEMBL3613712
7.14	IC50	72	nM	CHEMBL3613711
7.10	IC50	79.43	nM	CHEMBL3613711
7.04	IC50	92	nM	CHEMBL3613709
7.00	IC50	100	nM	CHEMBL3613709
6.90	IC50	125.9	nM	CHEMBL2376321
6.69	IC50	205	nM	CHEMBL3613709
6.69	IC50	204.2	nM	CHEMBL3613709
6.44	IC50	365	nM	CHEMBL3613710
6.41	IC50	394	nM	CHEMBL3613712
6.41	IC50	389.1	nM	CHEMBL3613712
6.40	IC50	398.1	nM	CHEMBL2376325
6.40	IC50	398.1	nM	CHEMBL3613710
6.22	IC50	597	nM	CHEMBL3613708
6.20	IC50	631	nM	CHEMBL3613703
6.20	IC50	631	nM	CHEMBL3613708
6.17	IC50	682	nM	CHEMBL3613703
6.12	IC50	760	nM	CHEMBL3613711
6.10	IC50	794.3	nM	CHEMBL3613711
5.60	IC50	2512	nM	CHEMBL2376322
5.60	IC50	2512	nM	CHEMBL3613704
5.56	IC50	2740	nM	CHEMBL3613704
5.42	IC50	3837	nM	CHEMBL3613705
5.40	IC50	3981	nM	CHEMBL3613705

PubChem BioAssay actives

30 with measured affinity, of 40 total; 14 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
2-[2-(3-methoxyphenyl)acetyl]-N-(2-phenyltriazol-4-yl)-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.0060	uM
N-[2-(4-fluorophenyl)triazol-4-yl]-2-[2-(3-methoxyphenyl)acetyl]-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.0060	uM
(3S)-N-(2,4-difluorophenyl)-3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745092: Inhibition of human recombinant MGAT3 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
N-[2-(3,3-difluorocyclobutyl)triazol-4-yl]-2-[2-(3-methoxyphenyl)acetyl]-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.0630	uM
2-[2-(3-methoxyphenyl)acetyl]-N-[2-(oxan-3-yl)triazol-4-yl]-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.0720	uM
N-(2-cyclobutyltriazol-4-yl)-2-[2-(3-methoxyphenyl)acetyl]-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.0920	uM
(3S)-N-[4-(difluoromethoxy)phenyl]-3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745092: Inhibition of human recombinant MGAT3 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	0.1259	uM
2-[2-(3-methoxyphenyl)acetyl]-N-[2-(oxetan-3-yl)triazol-4-yl]-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.3650	uM
N-(4-chlorophenyl)-3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745092: Inhibition of human recombinant MGAT3 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
2-[2-(3-methoxyphenyl)acetyl]-N-(2-propan-2-yltriazol-4-yl)-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.5970	uM
N-[2-(3-fluorophenyl)ethyl]-2-[2-(3-methoxyphenyl)acetyl]-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	0.6310	uM
N-[2-(3-fluorophenyl)ethyl]-2-[2-(3-methoxyphenyl)acetyl]-N-methyl-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	2.5119	uM
3-ethyl-3-methyl-2,5-dioxo-N-phenyl-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide	745092: Inhibition of human recombinant MGAT3 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	2.5119	uM
2-[2-(3-methoxyphenyl)acetyl]-N-(2-methyltriazol-4-yl)-1,3-dihydroisoindole-5-sulfonamide	1244858: Inhibition of MGAT3 (unknown origin) assessed effect on incorporation of [1-14C]decanoyl moiety into triacylglycerol using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates pre-incubated for 30 mins before substrate addition	ic50	3.8370	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases expression	4
Cisplatin	affects expression, affects cotreatment, increases expression	3
bisdemethoxycurcumin	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Silicon Dioxide	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
7-(4,6-di-tert-butylpyrimidin-2-yl)-3-(4-trifluoromethoxyphenyl)-5,6,7,8-tetrahydro(1,2,4)triazolo(4,3-a)pyrazine	affects activity	1
bisphenol A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
perfluorobutanesulfonic acid	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Acetaminophen	decreases expression	1
Cadmium	increases expression	1
Carmustine	decreases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Zearalenone	increases expression	1
Zinc	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2378967	Binding	Inhibition of human recombinant MGAT3 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

Clinical trials (associated diseases)

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