FUT2

Galactoside 2-alpha-L-fucosyltransferase 2 is an enzyme that in humans is encoded by the FUT2 (fucosyltransferase 2) gene.^[5][6]

FUT2
Identifiers
Aliases	FUT2, B12QTL1, SE, SEC2, Se2, sej, fucosyltransferase 2
External IDs	OMIM: 182100; MGI: 109374; HomoloGene: 10325; GeneCards: FUT2; OMA:FUT2 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.33 Start 48,695,971 bp[1] End 48,705,951 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 B3|7 29.41 cM Start 45,298,015 bp[2] End 45,315,818 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in olfactory zone of nasal mucosa nasal epithelium minor salivary glands pancreatic ductal cell mucosa of transverse colon buccal mucosa cell duodenum oral cavity rectum palpebral conjunctiva Top expressed in lip left colon epithelium of stomach skin of external ear seminal vesicula duodenum esophagus migratory enteric neural crest cell skin of back lobe of prostate More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity galactoside 2-alpha-L-fucosyltransferase activity glycosyltransferase activity fucosyltransferase activity Cellular component integral component of membrane Golgi cisterna membrane Golgi apparatus extracellular exosome membrane Biological process protein glycosylation L-fucose catabolic process fucosylation carbohydrate metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2524 14344 Ensembl ENSG00000176920 ENSMUSG00000055978 UniProt Q10981 Q9JL27 RefSeq (mRNA) NM_001097638 NM_000511 NM_001271993 NM_018876 RefSeq (protein) NP_000502 NP_001091107 NP_001258922 NP_061364 Location (UCSC) Chr 19: 48.7 – 48.71 Mb Chr 7: 45.3 – 45.32 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

FUT2 is a key enzyme that catalyzes the transfer of L-fucose from guanosine diphosphate-beta-L-fucose to the terminal galactose on both O- and N-linked glycans of cell surface glycoproteins and glycolipids. This enzymatic activity is essential for the synthesis of the H antigen, a precursor required for the formation of ABO blood group antigens,^[7] and determines "secretor status"—the presence of blood group antigens in bodily fluids such as saliva. Beyond its role in blood group antigen synthesis, FUT2 influences cell-cell interactions, modulates the composition of the gut microbiome, and impacts susceptibility to infections and autoimmune diseases, highlighting its broad significance in human health and disease.

Approximately 20% of Caucasians are non-secretors due to the G428A (rs601338) and C571T (rs492602?) nonsense mutations in FUT2 and therefore have strong although not absolute protection from the norovirus GII.4.^{[citation needed]}\

Role in secretor status

The FUT2 gene determines an individual's secretor status by encoding an enzyme responsible for the expression of histo-blood group antigens in bodily secretions. Approximately 70–80% of people are secretors, meaning they possess at least one functional FUT2 allele.^[8] Those who are homozygous for a nonfunctional allele are termed non-secretors, which has important health implications.

Clinical signficance

Non-secretors display altered susceptibility to both infectious and autoimmune diseases. While they exhibit increased resistance to certain viral pathogens like norovirus,^[8] they are more prone to developing chronic inflammatory conditions such as Crohn’s disease^[9][10] and type 1 diabetes.^[11]

Impact on the gut microbiome

Loss-of-function mutations in FUT2 dramatically alter the composition of the gut microbiome. Non-secretors have distinct microbial profiles compared to secretors, with studies reporting a reduction in Escherichia species and a rise in pro-inflammatory taxa.^[12] Notably, non-secretors also exhibit increased levels of butyrate-producing bacteria, which are generally considered beneficial.

Consequences for microbial metabolism

Although FUT2 does not directly regulate microbial metabolism, its influence on microbial community structure can indirectly affect metabolite production. The enrichment of butyrate producers in non-secretors may represent a compensatory mechanism, but this benefit may be insufficient to counterbalance the elevated inflammatory potential of the overall microbiome. Thus, FUT2 loss-of-function variants may skew the microbiome toward a pro-inflammatory state, potentially exacerbating conditions such as inflammatory bowel disease (IBD) and masking the protective effects of beneficial metabolites like butyrate.