Identification and protein modelling analysis of a homozygous FUT1*01W.09 variant in a Thai patient with the para‐Bombay phenotype

Objective To characterise a Thai patient with a para‐Bombay phenotype associated with homozygosity for a variant FUT1 allele and explore the underlying mechanism of reduced enzymatic activity. Background The para‐Bombay phenotype is a rare red blood cell phenotype characterised by absent or markedly reduced ABH antigens on erythrocytes, with preserved expression in secretions, typically resulting from FUT1 mutations affecting α1,2‐L‐fucosyltransferase 1 (α1,2FucT1). Materials and Methods Serological testing was performed using standard methods. ABO , FUT1 and FUT2 genotypes were determined by whole‐exome and Sanger sequencing. Structural modelling of the FUT1 variant was conducted using AlphaFold3 and ChimeraX, and functional effects were predicted using ProtVar. Results Serology identified a para‐Bombay B h phenotype with anti‐HI and autoantibodies. Genotyping revealed homozygosity for ABO*B.01 , FUT1 c.658C>T (p.Arg220Cys; rs574691621; FUT1*01W.09 ), and FUT2 c.390C>T (a silent variant, p.Asn130). Structural modelling suggested that the p.Cys220 substitution does not alter overall protein conformation or stability but may impair substrate binding and local intermolecular interactions. Conclusion This report presents the first Thai case of para‐Bombay B h phenotype associated with homozygosity for the weakened FUT1*01W.09 allele. In silico modelling predicted that the variant impairs α1,2FucT1 activity and substrate binding without compromising protein stability, supporting safe transfusion practice.