FUT1

FUT1 is the gene that encodes the enzyme alpha-1,2-fucosyltransferase 1, a member of the fucosyltransferase family. The enzyme catalyzes the transfer of a fucose sugar in an alpha-1,2 linkage to precursor glycans, generating the H antigen that forms the foundation of the ABO blood group system.

In humans, FUT1 is located on chromosome 19q13.3 and produces a type II membrane protein that resides in the Golgi apparatus. It uses GDP-fucose as its donor substrate and acts on precursor glycan chains to form the H antigen on red blood cell surfaces and various tissues. The H antigen produced by FUT1 serves as the substrate for the A and B transferases that determine ABO blood types and also contributes to ABO antigen expression on tissues that express secretor status.

Genetic variation in FUT1 can have important clinical consequences. Biallelic loss-of-function mutations in FUT1 cause the Bombay (Oh) phenotype, in which individuals lack H antigen on red blood cells and in many secretions, and consequently produce potent anti-H antibodies that complicate transfusions. The Bombay phenotype is extremely rare and is typically identified serologically by its distinct reaction pattern with ABO reagents. A related, more variable condition is the para-Bombay phenotype, where H antigen expression is weak or restricted, often due to partial FUT1 activity or tissue-specific expression differences.

FUT1 function is closely linked to other related glycosyltransferases, including FUT2 (secretor FUT) and FUT3 (Lewis group enzymes), which together influence tissue-specific and secreted blood group antigen expression. Understanding FUT1 aids in the interpretation of uncommon blood group phenotypes and transfusion compatibility.