MGAT5

Summary

MGAT5 (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase, HGNC:7049) is a protein-coding gene on chromosome 2q21.2-q21.3, encoding Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (Q09328). Catalyzes the addition of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides.

The protein encoded by this gene belongs to the glycosyltransferase family. It catalyzes the addition of beta-1,6-N-acetylglucosamine to the alpha-linked mannose of biantennary N-linked oligosaccharides present on the newly synthesized glycoproteins. It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. Alterations of the oligosaccharides on cell surface glycoproteins cause significant changes in the adhesive or migratory behavior of a cell. Increase in the activity of this enzyme has been correlated with the progression of invasive malignancies.

Source: NCBI Gene 4249 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 79 total
• Druggable target: yes
• MANE Select transcript: NM_002410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7049
Approved symbol	MGAT5
Name	alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase
Location	2q21.2-q21.3
Locus type	gene with protein product
Status	Approved
Aliases	GNT-V, MGAT5A
Ensembl gene	ENSG00000152127
Ensembl biotype	protein_coding
OMIM	601774
Entrez	4249

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000281923, ENST00000409645, ENST00000468758, ENST00000481801, ENST00000488365, ENST00000857190, ENST00000857191

RefSeq mRNA: 2 — MANE Select: NM_002410 NM_001371457, NM_002410

CCDS: CCDS2171

Canonical transcript exons

ENST00000281923 — 16 exons

Exon	Start	End
ENSE00001071439	134254072	134254644
ENSE00003889272	134336217	134336288
ENSE00003889667	134270386	134270550
ENSE00003890180	134344930	134345064
ENSE00003890435	134412869	134413015
ENSE00003891876	134362275	134362408
ENSE00003893387	134402988	134403137
ENSE00003893569	134448649	134454621
ENSE00003893930	134349805	134349938
ENSE00003894143	134422803	134422919
ENSE00003894581	134338259	134338420
ENSE00003894761	134428365	134428439
ENSE00003895544	134317529	134317605
ENSE00003895851	134441758	134441915
ENSE00003895878	134341590	134341759
ENSE00003896035	134318650	134318739

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.5585 / max 438.8294, expressed in 1794 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22576	9.9582	1745
22577	5.7396	1512
22581	2.1963	1169
22578	1.9923	1001
22575	1.2485	830
22580	0.4957	242
22579	0.4373	215
22588	0.2155	39
22589	0.0909	28
22591	0.0855	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal glomerulus	UBERON:0000074	99.10	gold quality
metanephric glomerulus	UBERON:0004736	99.03	gold quality
middle temporal gyrus	UBERON:0002771	97.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.89	gold quality
tibia	UBERON:0000979	96.73	gold quality
pons	UBERON:0000988	95.53	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.41	gold quality
bronchial epithelial cell	CL:0002328	95.19	gold quality
inferior olivary complex	UBERON:0002127	95.18	gold quality
left ventricle myocardium	UBERON:0006566	95.18	gold quality
pancreatic ductal cell	CL:0002079	95.11	gold quality
heart right ventricle	UBERON:0002080	95.07	gold quality
substantia nigra pars compacta	UBERON:0001965	95.02	gold quality
inferior vagus X ganglion	UBERON:0005363	94.98	gold quality
visceral pleura	UBERON:0002401	94.74	gold quality
epithelium of bronchus	UBERON:0002031	94.57	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.34	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.31	gold quality
bronchus	UBERON:0002185	94.23	gold quality
lateral globus pallidus	UBERON:0002476	94.08	gold quality
epithelium of nasopharynx	UBERON:0001951	94.07	gold quality
nasopharynx	UBERON:0001728	94.05	gold quality
superior vestibular nucleus	UBERON:0007227	93.94	gold quality
superficial temporal artery	UBERON:0001614	93.88	gold quality
ileal mucosa	UBERON:0000331	93.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.82	gold quality
medulla oblongata	UBERON:0001896	93.78	gold quality
jejunal mucosa	UBERON:0000399	93.77	gold quality
parotid gland	UBERON:0001831	93.67	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	43.77
E-ANND-3	yes	12.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF4, ETS1, ETS2, ETV7, JUN, TBXT, ZHX2

miRNA regulators (miRDB)

185 targeting MGAT5, 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-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358

Literature-anchored findings (GeneRIF, showing 40)

• Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching (PMID:11864986)
• A secreted type of beta 1,6-N-acetylglucosaminyltransferase V (GnT-V) induces tumor angiogenesis without mediation of glycosylation: a novel function of GnT-V distinct from the original glycosyltransferase activity. (PMID:11872751)
• Low GnT-V expression is associated with shorter survival and poor prognosis in pStage I overall Non-small cell lung cancer. (PMID:15014031)
• Data describe the effect of N-acetylglucosaminyltransferase V on the expressions of other glycosyltransferases involved in the synthesis of surface sialyl Lewis X antigen. (PMID:15044007)
• GlcNAc-transferase-V activity is up-regulated in RA and Vit-D(3)-treated hepatoma cell lines. (PMID:15313475)
• GnT-V would contribute to placentation in the early phase of pregnancy, possibly regulating the process of invasion of trophoblast cells (PMID:15809094)
• These results supported the mechanism that blocking of GnT-V expression impaired functions of chaperones and N-glycan-synthesizing enzymes, which caused UPR in vivo. (PMID:16467879)
• GnT-V is closely related to low malignant potential and good prognosis of the patients with bladder cancer. (PMID:16638859)
• Glycosylation caused by GnT-V directs integrin beta1 stability and more delivery to plasma membrane, subsequently promotes Fn-based cell migration and invasion. (PMID:16924681)
• glycosylation change & decrease of transport activity of GLUT1 may be 1 possible mechanism of ER stress induced by down-regulating GnT-V, & GnT-V may contribute to the regulation of glucose uptake by modifying glycosylation of GLUT1 in some tumor cells. (PMID:17451637)
• We investigated mRNA levels of glycosyltransferases, namely GnT-V, and found that it’s expression was decreased in HLE-cells resistant to Epirubicin as well as in HLE-cells resistant to Mitoxantrone. (PMID:17488527)
• Tissue inhibitor of metalloproteinase-1 (TIMP-1), was identified as a target protein for GnT-V in human colon cancer cell WiDr. (PMID:17878270)
• Results suggested that high GnT-V expression was correlated with an unfavourable clinical outcome. (PMID:17971775)
• Knock-down of MGAT5 in PC-3 cells attenuated the metastatic ability of prostate cancer cells, as determined by the in vitro invasion assay and the xenograft animal studies. (PMID:18649738)
• GnT-V is expressed in human extravillous trophoblast and is involved in regulating trophoblast invasion through modifications of the oligosaccharide chains of alpha5beta1 integrin. (PMID:18845630)
• GnT-V expression is correlated with a poor prognosis in gastric cancer patients due to metastases. (PMID:18931531)
• decreased GnT-Va activity due to siRNA expression in human carcinoma cells inhibits ligand-induced EGFR internalization, consequently resulting in delayed downstream signal transduction and inhibition of the EGF-induced, invasiveness-related phenotypes. (PMID:19225046)
• overexpression of GnT-V in a hepatoma cell line not only induced the addition of beta1,6 GlcNAc branch to N-glycan of RPTPkappa but also decreased the protein level of RPTPkappa (PMID:19236842)
• MGAT3 and MGAT5 competitively modified E-cadherin N-glycans. (PMID:19403558)
• High expression of N-acetylglucosaminyltransferase V is associated with mucinous tumors of the ovary. (PMID:19787216)
• The GnT-V was fully active without exogenous cation and in the presence of EDTA, and pH optimum for GnT-V was in the range of 6.5-7.0. (PMID:19846580)
• Our results suggest that GnT-V could decrease human hepatoma SMMC-7721 cell adhesion and promote cell proliferation partially through RPTPkappa. (PMID:19911372)
• 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)
• Inhibiting expression of N-acetylglucosaminyltransferase V inhibits the proliferation of PC-3 cells. (PMID:20584650)
• The rs1257169(G) allele of MGAT5 is associated with lower disease severity in multiple sclerosis (PMID:21115203)
• Findings suggest Mgat5 may play an important role during oncogenesis, identifying a potential therapeutic target for pulmonary adenocarcinoma. (PMID:21631992)
• GnT-V expression is positively correlated with malignancy in nasopharyngeal carcinoma cells (PMID:21676538)
• 33 directly measured and 13 derived glycosylation traits in 3533 individuals were identified and three novel gene association (MGAT5, B3GAT1 and SLC9A9) were identified using an additional European cohort. (PMID:21908519)
• These data suggested that GnT-V expression was positively related with malignancy in human hepatocellular carcinoma (HCC) and GnT-V may be both a differentiation marker and a potential target for the treatment of HCC. (PMID:22537550)
• decreased GnT-V activity due to inflammatory cytokine induction in human monocytes resulted in enchancement of integrin alpha5beta1-dependent monocyte-vascular endothelium adhesion and transmigration (PMID:22614033)
• The results suggest that GnT-V may be a potential target for predicting nasopharyngeal carcinoma response to radiotherapy. (PMID:22780953)
• Data show that knockdown of CD147 inhibited MMP-2 activity of GnT-V-overexpressing cells, indicating that aberrant beta1,6-branches on CD147 is crucial for the induction of MMPs (matrix metalloproteinases) in SMMC-7721 cells. (PMID:23005037)
• The combination of intratumoral MGAT5 expression and TNM or Kiel staging systems had a better predictive power for overall survival. (PMID:23107376)
• The results of this study have shown that the MGAT5 intronic variants rs4953911 and rs3814022 correlate with lower N-glycan branching, reduced surface CTLA-4 in human CD4 + T cell blasts, and associate with multiple sclerosis. (PMID:23351704)
• GnT-V directs cancer progression by modulating MMPs in cancer. (PMID:23357422)
• GnT-V plays a significant role in metastasis and invasion in gastric cancer cells. (PMID:23563846)
• GnT-III determines E-cadherin-mediated tumor suppression, and GnT-V regulates E-cadherin-mediated tumor invasion. (PMID:23671930)
• The results identified Mgat5-mediated beta-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells. (PMID:23811795)
• Study disclose that a deficiency in branched N-glycosylation on TCR due to a reduced MGAT5 gene expression is a new molecular mechanism underlying UC pathogenesis. (PMID:24334766)
• These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications. (PMID:24399258)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mgat5	ENSMUSG00000036155
rattus_norvegicus	Mgat5	ENSRNOG00000003614
caenorhabditis_elegans	gly-2	WBGENE00001627

Paralogs (2): MGAT5B (ENSG00000167889), CCDC126 (ENSG00000169193)

Protein

Protein identifiers

Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A — Q09328 (reviewed: Q09328)

Alternative names: Alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase V, GlcNAc-T V, Mannoside acetylglucosaminyltransferase 5, N-acetylglucosaminyl-transferase V

All UniProt accessions (1): Q09328

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the addition of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides. Catalyzes an important step in the biosynthesis of branched, complex-type N-glycans, such as those found on EGFR, TGFR (TGF-beta receptor) and CDH2. Via its role in the biosynthesis of complex N-glycans, plays an important role in the activation of cellular signaling pathways, reorganization of the actin cytoskeleton, cell-cell adhesion and cell migration. MGAT5-dependent EGFR N-glycosylation enhances the interaction between EGFR and LGALS3 and thereby prevents rapid EGFR endocytosis and prolongs EGFR signaling. Required for efficient interaction between TGFB1 and its receptor. Enhances activation of intracellular signaling pathways by several types of growth factors, including FGF2, PDGF, IGF, TGFB1 and EGF. MGAT5-dependent CDH2 N-glycosylation inhibits CDH2-mediated homotypic cell-cell adhesion and contributes to the regulation of downstream signaling pathways. Promotes cell migration. Contributes to the regulation of the inflammatory response. MGAT5-dependent TCR N-glycosylation enhances the interaction between TCR and LGALS3, limits agonist-induced TCR clustering, and thereby dampens TCR-mediated responses to antigens. Required for normal leukocyte evasation and accumulation at sites of inflammation. Inhibits attachment of monocytes to the vascular endothelium and subsequent monocyte diapedesis. Promotes proliferation of umbilical vein endothelial cells and angiogenesis, at least in part by promoting the release of the growth factor FGF2 from the extracellular matrix.

Subcellular location. Golgi apparatus membrane Secreted.

Post-translational modifications. N-glycosylated. A secreted form is released from the membrane after cleavage by gamma-secretase.

Activity regulation. Activity is increased by Mn(2+) and Mg(2+).

Induction. Induced by IFNG treatment in monocytes (in vitro).

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 18 family.

RefSeq proteins (2): NP_001358386, NP_002401* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026116	GT18_cat	Domain
IPR027833	MGT5A-like_N	Domain
IPR052105	MGAT5_Glycosyltransferase	Family

Pfam: PF15024, PF15027

Enzyme classification (BRENDA):

• EC 2.4.1.155 — alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase (BRENDA: 6 organisms, 95 substrates, 31 inhibitors, 37 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
UDP-N-ACETYLGLUCOSAMINE	3.5–11	7
N-ACETYL-D-GLUCOSAMINYL-1,2-ALPHA-D-MANNOSYL-1,3	0.13–0.23	4
AC-VAL-GLU-PRO-(GLCNACBETA(1-2)MANALPHA1-O-)THR-	0.05–1.11	2
GLCNAC-BETA(1-2)MAN-ALPHA(1-3)(GLCNAC-BETA(1-2)M	1.28–2.4	2
GLCNACBETA(1-2)MANALPHA(1-2)GLC-O-OCTYL	0.53–1.82	2
GLCNACBETA(1-2)MANALPHA1-O-BENZYL	0.61–0.88	2
N-ACETYL-D-GLUCOSAMINYL-1,2-ALPHA-MANNOSYL-1,6-B	0.023–0.036	2
UDP-GLCNAC	4.5–5.8	2
UDP-N-ACETYL-D-GLUCOSAMINE	0.56–1.62	2
GLCNACBETA(1->2)MANALPHA(1->3)-[GLCNACBETA(1->2)	0.133	1
N-ACETYL-D-GLUCOSAMINE	0.25	1
N-ACETYL-D-GLUCOSAMINYL-1,2-ALPHA-4-DEOXY-MANNOS	0.074	1
N-ACETYL-D-GLUCOSAMINYL-1,2-ALPHA-MANNOSYL-1,6-B	0.18	1
N-ACETYL-D-GLUCOSAMINYL-1,2-ALPHA-MANNOSYL-1,6-B	0.087	1
TDP-GLUCOSE	2.9	1

Catalyzed reactions (Rhea), 1 shown:

• N(4)-{beta-D-GlcNAc-(1->2)-[beta-D-GlcNAc-(1->4)]-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)-[beta-D-GlcNAc-(1->4)]-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-[beta-D-GlcNAc-(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:16921)

UniProt features (92 total): helix 35, strand 19, disulfide bond 9, mutagenesis site 9, glycosylation site 6, turn 4, binding site 3, chain 2, topological domain 2, region of interest 2, transmembrane region 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6YJS	X-RAY DIFFRACTION	1.6
6YJT	X-RAY DIFFRACTION	1.7
6YJV	X-RAY DIFFRACTION	1.7
8CE3	X-RAY DIFFRACTION	1.89
5ZIB	X-RAY DIFFRACTION	1.9
6YJQ	X-RAY DIFFRACTION	1.9
6YJU	X-RAY DIFFRACTION	1.96
9F5H	X-RAY DIFFRACTION	1.97
5ZIC	X-RAY DIFFRACTION	2.1
6YJR	X-RAY DIFFRACTION	2.2
7YYI	SOLUTION NMR
7Z07	SOLUTION NMR
7Z08	SOLUTION NMR
7Z0B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q09328-F1	83.91	0.58

Functional residue map

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

Ligand- & substrate-binding residues (3): 378–379; 526; 554

Disulfide bonds (9): 145–183, 156–196, 172–338, 372–626, 649–724, 653–726, 660–713, 681–702, 737–740

Glycosylation sites (6): 110, 115, 118, 334, 433, 447

Mutagenesis-validated functional residues (9):

Position	Phenotype
29	no effect on the biosynthesis of the secreted form.
30	no effect on the biosynthesis of the secreted form.
31	no effect on the biosynthesis of the secreted form.
280	decreased catalytic activity.
287	decreased catalytic activity.
297	loss of catalytic activity.
429	decreased catalytic activity.
520	loss of catalytic activity.
526	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-9694548	Maturation of spike protein
R-HSA-975577	N-Glycan antennae elongation
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-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9694635	Translation of Structural Proteins
R-HSA-975576	N-glycan antennae elongation in the medial/trans-Golgi
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 203 (showing top): ZHAN_MULTIPLE_MYELOMA_MF_UP, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, BROWN_MYELOID_CELL_DEVELOPMENT_DN, HOOI_ST7_TARGETS_DN, CUI_TCF21_TARGETS_2_DN, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, MULLIGHAN_MLL_SIGNATURE_2_DN, CAIRO_LIVER_DEVELOPMENT_UP

GO Biological Process (6): protein N-linked glycosylation (GO:0006487), obsolete protein N-linked glycosylation via asparagine (GO:0018279), viral protein processing (GO:0019082), positive regulation of cell migration (GO:0030335), positive regulation of receptor signaling pathway via STAT (GO:1904894), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (6): protein phosphatase inhibitor activity (GO:0004864), alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase activity (GO:0030144), manganese ion binding (GO:0030145), acetylglucosaminyltransferase activity (GO:0008375), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Translation of Structural Proteins	1
N-glycan antennae elongation in the medial/trans-Golgi	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1
Viral Infection Pathways	1
SARS-CoV Infections	1
Late SARS-CoV-2 Infection Events	1
Transport to the Golgi and subsequent modification	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	2
glycoprotein biosynthetic process	1
viral process	1
viral gene expression	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
positive regulation of signal transduction	1
cell surface receptor signaling pathway via STAT	1
regulation of receptor signaling pathway via STAT	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
acetylglucosaminyltransferase activity	1
catalytic activity, acting on a glycoprotein	1
transition metal ion binding	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

2071 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MGAT5	MGAT3	Q09327	950
MGAT5	MGAT4B	Q9UQ53	925
MGAT5	MGAT4A	Q9UM21	917
MGAT5	LGALS3	P17931	890
MGAT5	MGAT1	P26572	867
MGAT5	MGAT2	Q10469	785
MGAT5	FUT8	Q9BYC5	773
MGAT5	ST6GAL1	P15907	732
MGAT5	POMGNT1	Q8WZA1	708
MGAT5	GCNT2	Q8N0V5	685
MGAT5	MAN2A1	Q16706	667
MGAT5	B4GALT2	O60909	655
MGAT5	MAN2A2	P49641	629
MGAT5	ST3GAL4	Q11206	625
MGAT5	CDH1	P12830	622
MGAT5	LGALS9	O00182	622

IntAct

94 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TRAC	COCH	psi-mi:“MI:0914”(association)	0.530
MFF	MGAT5	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
ORF74	MGAT5	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
HLA-E	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
LYZL1	MANBA	psi-mi:“MI:0914”(association)	0.350
TMEM25	FUZ	psi-mi:“MI:0914”(association)	0.350
GPM6A	HAX1	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
SLC39A8	VAPB	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC7A14	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (121): MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A1H7M6, A1YGR5, A1YGR6, E9KID2, E9KID3, F4HXW9, G7LG31, O00469, O36022, O43909, O74745, P14769, P23336, P39107, P50127, P53697, P97259, Q00314, Q08834, Q09199, Q09328, Q1L8D2, Q3L7M0, Q3U4G3, Q494Q2, Q5GF25, Q5RD93, Q5SRI9, Q5ZLK4, Q6DE40, Q6NXH2, Q7YQE1, Q805R1, Q80RC7, Q811A3, Q866Z4, Q8H1E6, Q8LPF8, Q8R4G6, Q8W486

Diamond homologs: A2VE00, P97259, Q08834, Q09328, Q8BIS8, Q8R4G6, Q96EE4, Q3V5L5, Q765H6, Q9NDH7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-425366	7	19.8×	2e-05
SLC-mediated transmembrane transport	9	8.3×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	39.0×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4925 predictions. Top by Δscore:

Variant	Effect	Δscore
2:134120288:GGAG:G	donor_gain	1.0000
2:134120289:GAGG:G	donor_gain	1.0000
2:134120292:GTAAG:G	donor_loss	1.0000
2:134120293:T:G	donor_loss	1.0000
2:134317518:A:AG	acceptor_gain	1.0000
2:134317519:T:G	acceptor_gain	1.0000
2:134317523:TCACA:T	acceptor_loss	1.0000
2:134317524:CACA:C	acceptor_loss	1.0000
2:134317525:ACAG:A	acceptor_loss	1.0000
2:134317526:CA:C	acceptor_loss	1.0000
2:134317527:A:AC	acceptor_loss	1.0000
2:134317527:A:AG	acceptor_gain	1.0000
2:134317528:G:GG	acceptor_gain	1.0000
2:134317528:GAT:G	acceptor_gain	1.0000
2:134317604:AGGTA:A	donor_loss	1.0000
2:134317606:GT:G	donor_loss	1.0000
2:134318006:GGTT:G	donor_gain	1.0000
2:134318007:GTT:G	donor_gain	1.0000
2:134318008:TTT:T	donor_gain	1.0000
2:134318648:A:AG	acceptor_gain	1.0000
2:134318648:AGT:A	acceptor_gain	1.0000
2:134318648:AGTG:A	acceptor_gain	1.0000
2:134318649:G:GG	acceptor_gain	1.0000
2:134318649:GT:G	acceptor_gain	1.0000
2:134318649:GTG:G	acceptor_gain	1.0000
2:134318649:GTGG:G	acceptor_gain	1.0000
2:134338292:A:AG	acceptor_gain	1.0000
2:134338293:G:GG	acceptor_gain	1.0000
2:134338414:G:GT	donor_gain	1.0000
2:134338416:AGAAA:A	donor_gain	1.0000

AlphaMissense

4937 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:134254468:G:A	G22D	1.000
2:134254476:T:A	W25R	1.000
2:134254476:T:C	W25R	1.000
2:134317588:T:A	C156S	1.000
2:134317589:G:A	C156Y	1.000
2:134317589:G:C	C156S	1.000
2:134318652:G:C	W162C	1.000
2:134318652:G:T	W162C	1.000
2:134318667:G:C	W167C	1.000
2:134318667:G:T	W167C	1.000
2:134318728:T:G	Y188D	1.000
2:134318732:T:C	L189P	1.000
2:134336229:T:A	C196S	1.000
2:134336230:G:C	C196S	1.000
2:134338322:T:A	W237R	1.000
2:134338322:T:C	W237R	1.000
2:134338324:G:C	W237C	1.000
2:134338324:G:T	W237C	1.000
2:134341605:G:A	G275R	1.000
2:134341605:G:C	G275R	1.000
2:134341606:G:A	G275E	1.000
2:134341672:A:T	E297V	1.000
2:134341683:T:A	W301R	1.000
2:134341683:T:C	W301R	1.000
2:134341753:T:C	L324P	1.000
2:134344964:T:A	C338S	1.000
2:134344965:G:C	C338S	1.000
2:134345006:G:C	D352H	1.000
2:134345007:A:C	D352A	1.000
2:134345007:A:T	D352V	1.000

dbSNP variants (sampled 300 via entrez): RS1000016396 (2:134453289 G>C), RS1000019798 (2:134137703 A>G), RS1000038728 (2:134229971 A>G), RS1000040704 (2:134265292 A>G), RS1000042449 (2:134321622 G>A,T), RS1000043453 (2:134392322 T>C), RS1000044812 (2:134357894 G>T), RS1000049023 (2:134313180 C>T), RS1000060663 (2:134436445 G>T), RS1000093096 (2:134256317 T>C), RS1000095440 (2:134220405 T>A,C,G), RS1000115793 (2:134314519 G>A,C), RS1000121523 (2:134442307 G>A), RS1000136857 (2:134401641 A>G,T), RS1000140137 (2:134223197 T>A)

Disease associations

OMIM: gene MIM:601774 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000577_1	Multiple sclerosis (severity)	2.000000e-07
GCST001521_4	Subcutaneous adipose tissue	7.000000e-06
GCST003264_195	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST004283_8	Midgestational circulating levels of PCBs	5.000000e-06
GCST005046_19	N-glycan levels	2.000000e-10
GCST005046_20	N-glycan levels	2.000000e-10
GCST005046_32	N-glycan levels	3.000000e-09
GCST005046_33	N-glycan levels	3.000000e-09
GCST005790_85	Rosacea symptom severity	5.000000e-06
GCST006016_12	Serum alkaline phosphatase levels	9.000000e-11
GCST006479_94	Diverticular disease	2.000000e-06
GCST007400_9	Systemic lupus erythematosus	5.000000e-07
GCST008727_1	Chronic lymphocytic leukemia or systemic lupus erythematosus	7.000000e-09
GCST008729_1	Marginal zone lymphoma or systemic lupus erythematosus	3.000000e-08
GCST011353_36	Serum alkaline phosphatase levels	1.000000e-11
GCST012033_7	Sleep (1/3-day periodicity)	1.000000e-11
GCST90002382_75	Eosinophil percentage of white cells	4.000000e-09
GCST90011900_132	Serum alkaline phosphatase levels	2.000000e-38
GCST90013406_68	Liver enzyme levels (alkaline phosphatase)	7.000000e-38

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007042	polychlorinated biphenyls measurement
EFO:0007964	gestational serum measurement
EFO:0004999	N-glycan measurement
EFO:0009180	rosacea severity measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0009959	diverticular disease
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795131 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs661899	MGAT5		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, decreases reaction, increases activity, increases expression, decreases response to substance (+1 more)	5
Valproic Acid	affects cotreatment, increases expression	5
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sevoflurane	increases expression, increases reaction	1
Acetaminophen	increases expression	1
Cadmium	increases abundance, increases expression	1
Coumestrol	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	increases expression, increases reaction	1
Methotrexate	increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Propofol	increases expression, increases reaction	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
CHEMBL1809572	Binding	Activity at GnT-V expressed in human WiDr cells assessed per mg of protein after 4 hrs by Lineweaver-Burk plot	Synthesis and evaluation of a radioiodinated trisaccharide derivative as a synthetic substrate for a sensitive N-acetylglucosaminyltransferase V radioassay. — Bioorg Med Chem

Cellosaurus cell lines

9 cell lines: 8 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SY27	HAP1 MGAT5 (-)	Cancer cell line	Male
CVCL_VT65	CHO IM4/Vh	Transformed cell line	Female
CVCL_VT66	CHO IM4/Vm	Transformed cell line	Female
CVCL_VT67	CHO IM4/V/IV	Transformed cell line	Female
CVCL_VT68	CHO IM4/V/IV-G1	Transformed cell line	Female
CVCL_VT69	CHO IM4/V/IV-G2	Transformed cell line	Female
CVCL_VT70	CHO IM4/V/IV-G3	Transformed cell line	Female
CVCL_VT71	CHO IM4/V/IV-G4	Transformed cell line	Female
CVCL_VT72	CHO IM4/V/IV-G5	Transformed cell line	Female

Clinical trials (associated diseases)

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