FUT3 (Fucosyltransferase 3) Gene: Function, Disease Associations, and Expression
Explore the FUT3 gene, its role in Lewis antigen synthesis, associated diseases, tissue expression, and mutations.
Gene Information Card
| Symbol | FUT3 |
|---|---|
| Full Name | Fucosyltransferase 3 (Lewis blood group) |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 2525 ncbi.nlm.nih.gov/gene/2525 |
| Ensembl ID | ENSG00000171124 |
| UniProt ID | P21217 |
| OMIM ID | 111100 |
| HGNC ID | 4014 |
| Aliases | LE, Les, CD174, FucT-III, FT3B |
Description
The FUT3 gene encodes fucosyltransferase 3, a Golgi-resident enzyme that catalyzes the transfer of fucose to glycan precursors, leading to the synthesis of Lewis blood group antigens (Le(a) and Le(b)) and related fucosylated glycans. These antigens are expressed on the surface of epithelial cells and in body fluids, playing roles in cell-cell interactions, immune modulation, and host-pathogen recognition. Polymorphisms in FUT3 determine the Lewis blood group phenotype (Le(a+b-), Le(a-b+), Le(a-b-)) and have been associated with susceptibility to infections, cancer, and cardiovascular diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lewis Blood Group Incompatibility | Loss-of-function mutations in FUT3 result in the Le(a-b-) phenotype, leading to absence of Lewis antigens on red blood cells and epithelial surfaces. This can cause maternal-fetal incompatibility in rare cases. | OMIM, ClinVar |
| Gastric Cancer | FUT3 expression is altered in gastric cancer, affecting Lewis antigen expression on tumor cells. Loss of Le(b) expression is associated with increased risk of Helicobacter pylori infection and gastric carcinogenesis. | PubMed (via NCBI), COSMIC |
| Colorectal Cancer | Altered FUT3 expression and Lewis antigen profiles are observed in colorectal cancer, influencing tumor progression and metastasis. Specific FUT3 genotypes may modulate cancer risk. | PubMed (via NCBI), COSMIC |
| Infectious Diseases (e.g., Norovirus, H. pylori) | FUT3-dependent Lewis antigens serve as receptors for pathogens. Individuals with the Le(a-b-) phenotype are resistant to certain norovirus strains and H. pylori adhesion, affecting infection susceptibility. | PubMed (via NCBI) |
| Pancreatic Cancer | FUT3 expression is upregulated in pancreatic cancer, leading to increased sialyl Lewis antigen (sLe(a)) production, which is associated with poor prognosis and metastasis. | PubMed (via NCBI), COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 12.3 | Medium |
| Stomach | 10.1 | Medium |
| Small Intestine | 9.8 | Medium |
| Salivary Gland | 8.5 | Low |
| Lung | 6.2 | Low |
| Liver | 4.1 | Low |
| Kidney | 3.5 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line, high expression |
| A549 | 8.7 | Lung carcinoma, moderate expression |
| MCF7 | 5.3 | Breast cancer, low expression |
| HepG2 | 3.1 | Liver cancer, low expression |
| K562 | 1.2 | Leukemia, very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.59T>C (p.Leu20Pro) | Missense | ~5% in European populations | Loss of enzyme activity, leading to Le(a-b-) phenotype |
| c.202C>T (p.Arg68Cys) | Missense | ~10% in Asian populations | Reduced enzyme activity, altered Lewis antigen expression |
| c.314C>T (p.Thr105Met) | Missense | ~15% in African populations | Partial loss of function, affects Lewis antigen synthesis |
| c.508G>A (p.Gly170Ser) | Missense | Rare | Loss of function, associated with Le(a-b-) phenotype |
| c.667A>G (p.Ile223Val) | Missense | ~20% in European populations | Reduced enzyme activity, common polymorphism |
Mutation functional classification
Loss of Function (LOF)
Many missense mutations (e.g., p.Leu20Pro, p.Arg68Cys) result in complete or partial loss of fucosyltransferase activity, leading to the Lewis-negative phenotype (Le(a-b-)). These mutations often affect protein stability or catalytic residues.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FUT3. Overexpression of the wild-type enzyme in cancers can lead to increased sialyl Lewis antigen production, but this is not due to activating mutations.
Dominant Negative (DN)
No dominant-negative mutations have been described for FUT3. The enzyme functions as a monomer, and loss-of-function alleles are recessive at the phenotypic level.
View complete mutation data：
Gene Ontology (GO)
| • Fucosyltransferase activity (GO:0008417) | • Golgi membrane (GO:0000139) |
| • Integral component of membrane (GO:0016021) | • Carbohydrate metabolic process (GO:0005975) |
| • Protein glycosylation (GO:0006486) | • Blood group antigen biosynthesis (GO:0006688) |
Pathways
• Lewis blood group antigen biosynthesis
• Glycosphingolipid biosynthesis - lacto and neolacto series
• Metabolism of proteins (glycosylation)
Protein Summary
Fucosyltransferase 3 (FUT3) is a type II transmembrane protein localized to the Golgi apparatus. It catalyzes the transfer of fucose from GDP-fucose to type 1 glycan precursors, forming Lewis a (Le(a)) and Lewis b (Le(b)) antigens. The enzyme is critical for the synthesis of sialyl Lewis a (sLe(a)), a ligand for E-selectin, which is involved in leukocyte trafficking and cancer metastasis. FUT3 activity is regulated by the availability of GDP-fucose and the expression of other glycosyltransferases. The protein consists of a short N-terminal cytoplasmic tail, a transmembrane domain, and a large C-terminal catalytic domain. Mutations in FUT3 are responsible for the Lewis blood group polymorphism, which has implications in transfusion medicine and disease susceptibility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FUT3 Knockout HEK293 Cell Line | EDJ-KQ3402 | Human | 2525 | Details Get a Quote |
| POFUT3 Knockout HEK293 Cell Line | EDJ-KQ10189 | Human | 84750 | Details Get a Quote |
| POFUT3 Knockout HeLa Cell Line | EDJ-KQ36083 | Human | 84750 | Details Get a Quote |
| POFUT3 Knockout A-549 Cell Line | EDJ-KQ37327 | Human | 84750 | Details Get a Quote |
| POFUT3 Knockout HCT 116 Cell Line | EDJ-KQ37328 | Human | 84750 | Details Get a Quote |
| FUT3 Knockout HeLa Cell Line | EDJ-KQ53277 | Human | 2525 | Details Get a Quote |
| FUT3 Knockout A-549 Cell Line | EDJ-KQ61759 | Human | 2525 | Details Get a Quote |
| FUT3 Knockout HCT 116 Cell Line | EDJ-KQ70241 | Human | 2525 | Details Get a Quote |
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