MGAT3

Chr 22

beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase

Also known as: GNT-III, GNT3

NCBI Gene: 4248ENSG00000128268UniProt: Q09327

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. [provided by RefSeq, Jul 2008]

87
ClinVar variants
14
Pathogenic / LP
0.15
pLI score
0
Active trials
Clinical Summary— MGAT3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 61 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.63LOEUF
pLI 0.147
Z-score 2.56
OE 0.28 (0.14–0.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.13Z-score
OE missense 0.54 (0.48–0.61)
199 obs / 368.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.14–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.48–0.61)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 4 / 14.5Missense obs/exp: 199 / 368.2Syn Z: -0.13

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS61
Likely Benign5
Benign2
14
Pathogenic
61
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
57
4
0
61
Likely Benign
0
5
0
0
5
Benign
0
0
0
2
2
Total06218282

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MGAT3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Global analysis of human glycosyltransferases reveals novel targets for pancreatic cancer pathogenesis.
Gupta R et al.·Br J Cancer
2020
Investigating the Causal Effects of Exercise-Induced Genes on Sarcopenia.
Wang L et al.·Int J Mol Sci
2024
Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression.
Macke AJ et al.·Mol Cancer Res
2023
Multi-omics analysis and metastasis risk factor prediction in N1b stage PTMC: insights into immune infiltration and therapeutic implications.
Dai H et al.·Front Immunol
2025
Antagonistic and synergistic epigenetic modulation using orthologous CRISPR/dCas9-based modular system.
Josipović G et al.·Nucleic Acids Res
2019
Truncated, inactive N-acetylglucosaminyltransferase III (GlcNAc-TIII) induces neurological and other traits absent in mice that lack GlcNAc-TIII.
Bhattacharyya R et al.·J Biol Chem
2002
Bisected, complex N-glycans and galectins in mouse mammary tumor progression and human breast cancer.
Miwa HE et al.·Glycobiology
2013Functional
Differential Impact of Smoking on Methylome and Transcriptome in Crohn's Disease and Ulcerative Colitis.
Yan Ang Q et al.·Inflamm Bowel Dis
2024
CSF N-glycoproteomics for early diagnosis in Alzheimer's disease.
Palmigiano A et al.·J Proteomics
2016
DNA hypomethylation upregulates expression of the MGAT3 gene in HepG2 cells and leads to changes in N-glycosylation of secreted glycoproteins.
Klasić M et al.·Sci Rep
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Downregulation of MGAT3 Promotes Benzo[a]pyrene-Mediated Lung Carcinogenesis by Regulating Cell Invasion and Migration Activity.
Zhang S et al.·ACS Omega
2025🔓 Open Access
MGAT3 and MGAT5 overexpression alters the protein cargo of extracellular vesicles released by metastatic melanoma cells.
Wilczak M et al.·Biochem Biophys Res Commun
2025
Proximity Labeling-Based Identification of MGAT3 Substrates and Revelation of the Tumor-Suppressive Role of Bisecting GlcNAc in Breast Cancer via GLA Degradation.
Wang B et al.·Cells
2025🔓 Open Access
Circ_0070934 promotes MGAT3 expression and inhibits epithelial-mesenchymal transition in bronchial epithelial cells by sponging miR-199a-5p.
Ding Z et al.·Allergy Asthma Clin Immunol
2024🔓 Open Access
Exosomal miR‑663b exposed to TGF‑β1 promotes cervical cancer metastasis and epithelial‑mesenchymal transition by targeting MGAT3.
You X et al.·Oncol Rep
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools