MGAT5 Gene: Mannosyl (Alpha-1,6-)-Glycoprotein Beta-1,6-N-Acetyl-Glucosaminyltransferase V
Key regulator of N-glycan branching, implicated in cancer metastasis and immune modulation
Gene Information Card
| Symbol | MGAT5 |
|---|---|
| Full Name | Mannosyl (Alpha-1,6-)-Glycoprotein Beta-1,6-N-Acetyl-Glucosaminyltransferase V |
| Gene Type | Protein coding |
| Chromosomal Location | 2q21.3 |
| NCBI Gene ID | 4249 ncbi.nlm.nih.gov/gene/4249 |
| Ensembl ID | ENSG00000111341 |
| UniProt ID | Q09328 |
| OMIM ID | 600195 |
| HGNC ID | 7048 |
| Aliases | GnT-V, GNT-V, EC 2.4.1.155 |
Description
The MGAT5 gene encodes mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase V (GnT-V), a Golgi enzyme that catalyzes the addition of beta-1,6-N-acetylglucosamine to the alpha-1,6-mannose core of N-linked glycans. This modification produces tri- and tetra-antennary N-glycans, which are commonly upregulated in malignant transformation and metastasis. MGAT5 activity influences cell adhesion, migration, and immune signaling, making it a significant target in cancer research.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Increased MGAT5 expression leads to altered N-glycosylation of cell surface receptors (e.g., integrins, growth factor receptors), promoting invasion and metastasis. | COSMIC: frequent overexpression in various cancers; PubMed studies (e.g., breast, colon, lung) show correlation with poor prognosis. |
| Autoimmune disorders (e.g., multiple sclerosis, rheumatoid arthritis) | MGAT5 deficiency reduces T-cell receptor clustering and signaling threshold, leading to hyperactive immune responses. | Mouse models (Mgat5-/-) show enhanced autoimmune disease susceptibility; human studies link MGAT5 variants to autoimmune risk (OMIM 600195). |
| Congenital disorder of glycosylation (CDG) type II (rare) | Biallelic loss-of-function mutations in MGAT5 cause defective N-glycan branching, leading to developmental delay and neurological symptoms. | ClinVar: pathogenic variants reported; OMIM: 600195 (phenotype not fully characterized). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Low |
| Kidney | 8.5 | Low |
| Brain | 6.3 | Low |
| Lung | 12.4 | Medium |
| Colon | 15.7 | Medium |
| Breast | 9.8 | Low |
| Ovary | 11.0 | Medium |
| Pancreas | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 18.5 | High expression; associated with invasive phenotype |
| MCF7 (breast cancer) | 14.2 | Moderate; increased with metastatic potential |
| A549 (lung cancer) | 16.8 | High; correlates with migration |
| HepG2 (liver cancer) | 9.5 | Low baseline; inducible by oncogenic signals |
| Jurkat (T-cell leukemia) | 12.0 | Moderate; involved in T-cell activation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1265G>A (p.Arg422His) | Missense | 0.01% (gnomAD) | Reduced enzyme activity; potential impact on glycosylation |
| c.1843C>T (p.Arg615*) | Nonsense | Rare | Loss of function; associated with CDG-like phenotype |
| c.1021A>G (p.Thr341Ala) | Missense | 0.05% (gnomAD) | Uncertain; may affect substrate specificity |
| c.2201_2202insA (frameshift) | Insertion | Rare | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg615*, c.2201_2202insA) lead to truncated or non-functional protein, reducing N-glycan branching. This can cause immune dysregulation and CDG-like symptoms.
Gain of Function (GOF)
Amplification or overexpression of MGAT5 (not point mutations) is common in cancers, leading to increased GnT-V activity and enhanced metastatic potential.
Dominant Negative (DN)
No clear dominant-negative mutations reported; MGAT5 functions as a homodimer, but loss-of-function alleles are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • acetylglucosaminyltransferase activity (GO:0008375) | • Golgi apparatus (GO:0005794) |
| • protein glycosylation (GO:0006486) | • transferase activity (GO:0016757) |
| • Golgi membrane (GO:0000139) |
Pathways
• N-Glycan biosynthesis (KEGG: hsa00510)
• Metastatic cancer cell migration (Reactome: R-HSA-446219)
• T-cell receptor signaling (Reactome: R-HSA-202403)
Protein Summary
MGAT5 encodes GnT-V, a type II transmembrane glycosyltransferase localized to the Golgi apparatus. It catalyzes the transfer of N-acetylglucosamine to the alpha-1,6-mannose residue of N-glycans, generating beta-1,6-branched structures. These modifications are critical for cell surface receptor function, including integrin-mediated adhesion and growth factor signaling. Elevated GnT-V activity is a hallmark of aggressive cancers, while deficiency leads to immune hyperactivation. The protein is a potential therapeutic target for cancer and autoimmune diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MGAT5 Knockout HEK293 Cell Line | EDJ-KQ3012 | Human | 4249 | Details Get a Quote |
| MGAT5B Knockout HEK293 Cell Line | EDJ-KQ10487 | Human | 146664 | Details Get a Quote |
| MGAT5 Knockout A-549 Cell Line | EDJ-KQ24215 | Human | 4249 | Details Get a Quote |
| MGAT5 Knockout HCT 116 Cell Line | EDJ-KQ24216 | Human | 4249 | Details Get a Quote |
| MGAT5 Knockout HeLa Cell Line | EDJ-KQ24217 | Human | 4249 | Details Get a Quote |
| MGAT5B Knockout A-549 Cell Line | EDJ-KQ36595 | Human | 146664 | Details Get a Quote |
| MGAT5B Knockout HCT 116 Cell Line | EDJ-KQ37883 | Human | 146664 | Details Get a Quote |
| MGAT5B Knockout HeLa Cell Line | EDJ-KQ37884 | Human | 146664 | Details Get a Quote |
