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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MGAT4A
alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A
Chromosome 2 · 2q11.2
NCBI Gene: 11320Ensembl: ENSG00000071073.14HGNC: HGNC:7047UniProt: Q9UM21
32PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomealpha-1,3-mannosylglycoprotein 4-beta-N-acetylglucosaminyltransferase activityglycoprotein biosynthetic processprotein N-linked glycosylationCOVID-19smoking initiationAbruptio Placentaeobesity
✦AI Summary

MGAT4A is a glycosyltransferase that catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the core structure of N-linked glycans, creating β-1,4 branched N-glycan structures essential for protein glycosylation 1. The enzyme functions in the endoplasmic reticulum and Golgi apparatus, where it modifies numerous secretory and membrane proteins to generate tri- and tetra-antennary N-glycan structures 12. Mechanistically, MGAT4A-mediated N-glycosylation regulates protein-cell surface interactions through galectin binding. In endometrial cancer with TP53 mutations, MGAT4A overexpression increases GLUT1 glucose transporter N-glycosylation, enhancing galectin-9 binding and cell membrane localization, thereby promoting glucose uptake and cancer cell proliferation 3. Similarly, in cutaneous T-cell lymphoma, reduced MGAT4A expression decreases galectin-1 binding affinity, conferring apoptosis resistance to malignant T cells 4. Clinically, MGAT4A is dysregulated across multiple malignancies. MicroRNA-mediated suppression of MGAT4A (via miR-424 or let-7c) inhibits cell cycle progression and metastatic capacity in various cancers 56. Emerging evidence from Mendelian randomization studies identifies MGAT4A as a novel genetic target associated with type 1 diabetes risk 7, suggesting roles beyond glycoprotein structure in immune regulation.

Sources cited
1
MGAT4A catalyzes GlcNAc transfer to N-linked glycan core structures, creating β-1,4 branched arms and tri/tetra-antennary N-glycans
PMID: 17006639
2
MGAT4A functions as an N-glycan branching enzyme in mammalian secretory pathways with regulated activity
PMID: 38879010
3
MGAT4A is overexpressed in TP53-mutant endometrial cancer and promotes GLUT1 N-glycosylation, enhancing galectin-9 binding and glucose uptake
PMID: 39527463
4
Reduced MGAT4A expression in cutaneous T-cell lymphoma decreases galectin-1 binding and induces apoptosis resistance
PMID: 40155530
5
MGAT4A is identified as a novel genetic target associated with type 1 diabetes risk through immune cell transcriptomic analysis
PMID: 41299435
6
miR-424 directly targets MGAT4A; MGAT4A knockdown induces cell cycle arrest through CCND1 reduction, specific to β-1,4 branching
PMID: 26589799
7
let-7c miRNA represses MGAT4A expression to inhibit hepatocarcinoma cell metastatic and invasive ability through reduced N-glycosylation
PMID: 24769441
Disease Associationsⓘ20
COVID-19Open Targets
0.37Weak
smoking initiationOpen Targets
0.31Weak
Abruptio PlacentaeOpen Targets
0.31Weak
obesityOpen Targets
0.12Weak
placenta praeviaOpen Targets
0.07Suggestive
MODYOpen Targets
0.06Suggestive
hepatitis C virus infectionOpen Targets
0.06Suggestive
choriocarcinomaOpen Targets
0.06Suggestive
glycogen storage disease VIOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
hypoinsulinemic hypoglycemia and body hemihypertrophyOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.05Suggestive
type 2 diabetes mellitusOpen Targets
0.05Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.05Suggestive
lipodystrophy, congenital generalized, type 5Open Targets
0.05Suggestive
obesity due to melanocortin 4 receptor deficiencyOpen Targets
0.05Suggestive
hyperinsulinism-hyperammonemia syndromeOpen Targets
0.05Suggestive
CIDEC-related familial partial lipodystrophyOpen Targets
0.05Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MGAT5BProtein interaction99%MGAT3Protein interaction97%MGAT4DProtein interaction91%FUT8Protein interaction77%MGAT4BProtein interaction73%MGAT2Protein interaction73%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
37%
Brain
35%
Heart
24%
Liver
18%
Ovary
8%
Gene Interaction Network
Click a node to explore
MGAT4AMGAT5BMGAT3MGAT4DFUT8MGAT4BMGAT2
PROTEIN STRUCTURE
Preparing viewer…
PDB7XTL · 1.97 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.74LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.49 [0.33–0.74]
RankingsWhere MGAT4A stands among ~20K protein-coding genes
  • #11,544of 20,598
    Most Researched32
  • #5,853of 17,882
    Most Constrained (LOEUF)0.74
Genes detectedMGAT4A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
MGAT4A/Galectin9-Driven N-Glycosylation Aberration as a Promoting Mechanism for Poor Prognosis of Endometrial Cancer with TP53 Mutation.
PMID: 39527463
Adv Sci (Weinh) · 2024
1.00
2
sEV-mediated intercellular transformation from MGAT4A
PMID: 40155530
Oncogene · 2025
0.90
3
Immune cell-based transcriptomic Mendelian randomization and colocalization study on type 1 diabetes.
PMID: 41299435
BMC Med · 2025
0.80
4
Basigin is necessary for normal decidualization of human uterine stromal cells.
PMID: 36303457
Hum Reprod · 2022
0.70
5
Regulation of intracellular activity of N-glycan branching enzymes in mammals.
PMID: 38879010
J Biol Chem · 2024
0.60