# ABO histo-blood group glycosyltransferase
The ABO histo-blood group glycosyltransferase is the enzyme encoded by the human ABO gene on chromosome 9 (9q34.1) that synthesizes the A and B blood group antigens by adding a single sugar to the H antigen, a carbohydrate structure on the surface of red blood cells and many other tissues[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3595629/). Functional A alleles encode an α1,3-N-acetylgalactosaminyltransferase (A transferase, AT) and functional B alleles encode an α1,3-galactosyltransferase (B transferase, BT); O alleles produce no active enzyme[2](https://www.ncbi.nlm.nih.gov/books/NBK2267/) • [3](https://www.jstage.jst.go.jp/article/jmi/55/3%2C4/55_3%2C4_174/_pdf/-char/en). Which enzyme a person carries determines whether their red cells display A antigen, B antigen, both (group AB), or neither (group O), and thereby their ABO blood type[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3595629/).
| Key fact | Detail |
|---|---|
| Gene and locus | ABO, chromosome 9 at 9q34.1; protein-coding gene with seven exons and a 1062 bp coding sequence[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3595629/) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC305365/) |
| Reaction | Transfers N-acetyl-D-galactosamine (A) or D-galactose (B) from UDP-sugar donors, in α1→3 linkage, to the terminal galactose of H antigen structures on glycoproteins and glycolipids[5](https://www.sciencedirect.com/science/article/pii/S0021925818980361) • [3](https://www.jstage.jst.go.jp/article/jmi/55/3%2C4/55_3%2C4_174/_pdf/-char/en) |
| Antigen products | A antigen: GalNAcα1->3(Fucα1->2)Gal; B antigen: Galα1->3(Fucα1->2)Gal; group O retains H substance, Fucα1->2Gal[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/) |
| A versus B specificity | The A1 and B transferases differ at four amino acid positions (codons 176, 235, 266, and 268); residues 266 and 268 determine the sugar specificity[5](https://www.sciencedirect.com/science/article/pii/S0021925818980361) • [7](https://www.ncbi.nlm.nih.gov/books/NBK2267/pdf/) |
| O allele | A single nucleotide deletion, 261delG in exon 6, causes a frameshift and premature termination, yielding an inactive protein[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC305365/) |
| Enzyme family | The ABO-encoded proteins are the founders of glycosyltransferase family 6 (GT6)[8](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12044) |
| Allele diversity | Over 250 ABO alleles have been described, including alleles for A1, A2, A3, Ax, cis-AB, B(A), B3, and O phenotypes[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/) |
| Cofactor | Binds one Mn2+ ion per subunit[9](https://www.uniprot.org/uniprotkb/Q99482/entry) |
## Function in antigen biosynthesis
The ABO enzymes act at the last step of the sequential extension of oligosaccharide chains attached to glycoproteins or glycolipids[10](https://www.sciencedirect.com/science/article/pii/S1344622305000404). Their acceptor substrate is H substance, a terminal Fucα1->2Gal structure produced by fucosyltransferases encoded at the H and Se (secretor) loci[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/) • [11](https://onlinelibrary.wiley.com/doi/10.1111/ajt.13328). Both transferases are highly specific for this acceptor: they react with glycoconjugates carrying the terminal Fuc(α1-2)Gal group, and type 1 and 2 precursor chains lacking the (α1-2)-linked fucose are much less active as substrates[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC11345478/).
The A1 transferase transfers N-acetyl-D-galactosamine (GalNAc) from UDP-GalNAc to the H structure, creating the A antigen; the B transferase transfers D-galactose from UDP-galactose, creating the B antigen[5](https://www.sciencedirect.com/science/article/pii/S0021925818980361). Individuals with A, B, and AB phenotypes express the corresponding glycosyltransferase activity, whereas O individuals lack such activity, so the H antigen remains unmodified[13](https://pubmed.ncbi.nlm.nih.gov/2333095/).
## Structural basis of specificity
The A1 and B transferases are proteins differing in only four amino acids, at codons 176, 235, 266, and 268 (Arg-Gly-Leu-Gly in A versus Gly-Ser-Met-Ala in B), yet these changes switch the enzyme's sugar specificity[5](https://www.sciencedirect.com/science/article/pii/S0021925818980361) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC305365/). [In vitro](https://www.edgepedia.org/in-vitro) mutagenesis at codon 268 showed that this residue determines both activity and nucleotide-sugar donor specificity: substituting alanine into the B transferase produced an enzyme with both A and B activities, while a glutamic acid substitution abolished B transferase activity[5](https://www.sciencedirect.com/science/article/pii/S0021925818980361). The two enzymes are not perfectly discriminating: at elevated pH the B transferase can transfer the A-specific GalNAc onto H structures, and the A transferase can transfer small quantities of galactose, which explains the low levels of B determinants detectable on A1 red cells[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC11345478/).
## Alleles and subgroups
The three major alleles, A1, B, and O, were the first characterized at the molecular level, followed by the subgroups A2, A3, Ax, and B3 and the cis-AB and B(A) alleles, which specify expression of both A and B antigens from a single allele[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/). The A2 allele differs from A1 by a missense mutation (467C>T, Pro156Leu) and a single deletion (1061delC) in exon 7; the deletion causes a frameshift that disrupts the stop codon, producing a transferase extended by 21 further amino acid residues[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC305365/) • [14](https://pmc.ncbi.nlm.nih.gov/articles/PMC10767447/). Many other missense, nonsense, and frameshift mutations, as well as mutations altering mRNA splicing or promoter and enhancer activity, underlie the weak A and B subgroups[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/).
The subgroups differ quantitatively as well as qualitatively. A1, A2, and B transferases have different enzyme kinetics and compete for the same type II precursor substrates, giving an efficiency order of A1 > B > A2[11](https://onlinelibrary.wiley.com/doi/10.1111/ajt.13328). A1 and A2 gene products are also distinguishable kinetically, with different optimum pH values (6.0 versus 7.0) and metal requirements[15](https://pubmed.ncbi.nlm.nih.gov/823628/).
## Cloning and molecular genetics
The chemical nature of the A and B antigens was established in the late 1950s by Elvin Kabat and separately by Walter Morgan and [Winifred Watkins](https://www.edgepedia.org/winifred-watkins), and independently Ruggero Ceppellini, proposed that A and B glycosyltransferases synthesize the antigens from the common H precursor[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/). The definitive demonstration that alleles A and B encode these enzymes came in 1990, 90 years after [Karl Landsteiner](https://www.edgepedia.org/karl-landsteiner)'s discovery of the ABO blood groups, when Fumiichiro Yamamoto's team at the Biomembrane Institute cloned A, B, and O allelic cDNAs. [Henrik Clausen](https://www.edgepedia.org/henrik-clausen) initiated the project by isolating the group A transferase, whose partial amino acid sequence enabled expression cloning in HeLa cells, which carry the H acceptor substance on their surface[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/).
Cloning opened molecular ABO typing alongside classical serological phenotyping, and mutational analysis of alleles provided the structural basis of transferase activity and specificity[16](https://www.jstage.jst.go.jp/article/jasti/4/1/4_1_1/_article/-char/en). Olga Blumenfeld established the Blood group antigen Gene MUTation (BGMUT) database in 1997 to house blood group allele information, with Yamamoto as curator of the ABO system; over 250 ABO alleles were eventually deposited, and the International Society of Blood Transfusion adopted a similar allele nomenclature[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/). [Next-generation sequencing](https://www.edgepedia.org/next-generation-sequencing) has since identified numerous SNP variations in the coding and noncoding regions of the ABO gene, making it one of the most studied loci for human polymorphism[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/).
## Evolutionary context
ABO is a trans-species polymorphism: the antigens are polymorphic in many other primates, and in all species sequenced to date the same two amino acid changes are responsible for A and B specificity[17](https://arxiv.org/abs/1208.4613). The ABO-encoded proteins are classified as the founders of the CAZY glycosyltransferase family 6, and their polymorphism, first revealed by Landsteiner's blood groups, was described molecularly 90 years later[8](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12044).
## References
1. [A Brief History of Human Blood Groups, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3595629/)
2. [The ABO blood group, Blood Groups and Red Cell Antigens, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK2267/)
3. [E. Hosoi, ABO blood group system, Jpn J Med Immunol](https://www.jstage.jst.go.jp/article/jmi/55/3%2C4/55_3%2C4_174/_pdf/-char/en)
4. [Hosseini-Maaf et al. (2003), ABO exon and intron analysis in individuals with the AweakB phenotype, BMC Genetics](https://pmc.ncbi.nlm.nih.gov/articles/PMC305365/)
5. [Yamamoto et al., Amino acid residue at codon 268 determines both activity and nucleotide-sugar donor substrate specificity of human A and B transferases](https://www.sciencedirect.com/science/article/pii/S0021925818980361)
6. [Fumiichiro Yamamoto (2021), A historical overview of advances in molecular genetic/genomic studies of the ABO blood group system, Glycoconjugate Journal](https://pmc.ncbi.nlm.nih.gov/articles/PMC8578530/)
7. [The ABO blood group (PDF), NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK2267/pdf/)
8. [Blancher et al. (2013), Evolution of the ABO supergene family, ISBT Science Series](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12044)
9. [ABO glycosyltransferase Q99482, UniProtKB](https://www.uniprot.org/uniprotkb/Q99482/entry)
10. [ABO blood group alleles and genetic recombination, ScienceDirect](https://www.sciencedirect.com/science/article/pii/S1344622305000404)
11. [Jeyakanthan et al. (2015), Chemical Basis for Qualitative and Quantitative Differences Between ABO Blood Groups and Subgroups, American Journal of Transplantation](https://onlinelibrary.wiley.com/doi/10.1111/ajt.13328)
12. [ABO Blood System: Biosynthesis of Agglutinogenic Alkaline and Non-Agglutinogenic Acid Glycotopes, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11345478/)
13. [Molecular genetic basis of the histo-blood group ABO system, PubMed](https://pubmed.ncbi.nlm.nih.gov/2333095/)
14. [Allele-specific long-range sequencing as a method for ABO haplotyping, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC10767447/)
15. [Cartron (1976), Properties of alpha-N-acetylgalactosaminyltransferases in sera of group A and weak A subjects, PubMed](https://pubmed.ncbi.nlm.nih.gov/823628/)
16. [Fumiichiro Yamamoto (1999), ABO Blood Group System: Transition of Era from Immunoserology to Molecular Biology Triggered by ABO Gene Cloning, J-STAGE](https://www.jstage.jst.go.jp/article/jasti/4/1/4_1_1/_article/-char/en)
17. [Blood ties: ABO is a trans-species polymorphism in primates, arXiv](https://arxiv.org/abs/1208.4613)
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*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Enzyme classes and activities › Glycosyltransferases and glyco-enzyme activities › Glycosyltransferases › Galactosyltransferases › Blood-group galactosyltransferase activities*
*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 21, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license