ABO (gene)

Last updated
ABO
Protein ABO PDB 1lz0.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ABO , A3GALNT, A3GALT1, GTB, NAGAT, ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase), alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase
External IDs OMIM: 110300 MGI: 2135738 HomoloGene: 69306 GeneCards: ABO
EC number 2.4.1.37 2.4.1.40, 2.4.1.37
Orthologs
SpeciesHumanMouse
Entrez

28

80908

Ensembl

ENSG00000175164
ENSG00000281879

ENSMUSG00000015787

UniProt

P16442

P38649

RefSeq (mRNA)

NM_020469

NM_030718
NM_001290444

RefSeq (protein)

NP_065202

NP_001277373
NP_109643

Location (UCSC) Chr 9: 133.23 – 133.28 Mb Chr 2: 26.73 – 26.75 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Histo-blood group ABO system transferase is an enzyme with glycosyltransferase activity, which is encoded by the ABO gene in humans. [5] [6] It is ubiquitously expressed in many tissues and cell types. [7] ABO determines the ABO blood group of an individual by modifying the oligosaccharides on cell surface glycoproteins. Variations in the sequence of the protein between individuals determine the type of modification and the blood group. The ABO gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. [8]

Alleles

The ABO gene resides on chromosome 9 at the band 9q34.2 and contains 7 exons. [6] The ABO locus encodes three alleles, that is, 3 variants of the same gene. One allele is derived from each parent.

The A allele produces α-1,3-N-acetylgalactosamine transferase (A-transferase), which catalyzes the transfer of GalNAc residues from the UDP-GalNAc donor nucleotide to the Gal residues of the acceptor H antigen, converting the H antigen into A antigen in A and AB individuals.

The B allele encodes α-1,3-galactosyl transferase (B-transferase), which catalyzes the transfer of Gal residues from the UDP-Gal donor nucleotide to the Gal residues of the acceptor H antigen, converting the H antigen into B antigen in B and AB individuals. Remarkably, the difference between the A and B glycosyltransferase enzymes is only four amino acids. [9]

The O allele lacks both enzymatic activities because of the frameshift caused by a deletion of guanine-258 in the gene which corresponds to a region near the N-terminus of the protein. [10] This results in a frameshift and thus of a truncated protein of only 117 amino acids. [9] [11] The truncated protein is unable to modify oligosaccharides which end in fucose linked to galactose. Thus no A or B antigen is found in O individuals. This sugar combination is termed the H antigen. These antigens play an important role in the match of blood transfusion and organ transplantation. [9] Other minor alleles have been found for this gene. [6]

Common alleles

There are six common alleles in individuals of European descent. Nearly every living human's phenotype for the ABO gene is some combination of just these six alleles: [12] [13]

  • A
    • A101 (A1)
    • A201 (A2)
  • B
    • B101 (B1)
  • O
    • O01 (O1)
    • O02 (O1v)
    • O03 (O2)

Many rare variants of these alleles have been found in human populations around the world.

Clinical significance

In human cells, the ABO alleles and their encoded glycosyltransferases have been described in several oncologic conditions. [14] Using anti-GTA/GTB monoclonal antibodies, it was demonstrated that a loss of these enzymes was correlated to malignant bladder and oral epithelia. [15] [16] Furthermore, the expression of ABO blood group antigens in normal human tissues is dependent upon the type of differentiation of the epithelium. In most human carcinomas, including oral carcinoma, a significant event as part of the underlying mechanism is decreased expression of the A and B antigens. [17] Several studies have observed that a relative down-regulation of GTA and GTB occurs in oral carcinomas in association with tumor development. [17] [18] More recently, a genome wide association study (GWAS) has identified variants in the ABO locus associated with susceptibility to pancreatic cancer. [19] [20]

Clinical marker

A multi-locus genetic risk score study based on a combination of 27 loci, including the ABO gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). [8]

Related Research Articles

An allele, or allelomorph, is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule.

<span class="mw-page-title-main">Transferase</span> Class of enzymes which transfer functional groups between molecules

In biochemistry, a transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups from one molecule to another. They are involved in hundreds of different biochemical pathways throughout biology, and are integral to some of life's most important processes.

<span class="mw-page-title-main">ABO blood group system</span> Classification of blood types

The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 44 different blood type classification systems currently recognized by the International Society of Blood Transfusions (ISBT) as of December 2022. A mismatch in this, or any other serotype, can cause a potentially fatal adverse reaction after a transfusion, or an unwanted immune response to an organ transplant. The associated anti-A and anti-B antibodies are usually IgM antibodies, produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses.

α-Galactosidase Enzyme

α-Galactosidase is a glycoside hydrolase enzyme that catalyses the following reaction:

<span class="mw-page-title-main">Glycosyltransferase</span> Class of enzymes that catalyze the transfer of glycosyl groups to an acceptor

Glycosyltransferases are enzymes that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar to a nucleophilic glycosyl acceptor molecule, the nucleophile of which can be oxygen- carbon-, nitrogen-, or sulfur-based.

The Kell antigen system is a human blood group system, that is, a group of antigens on the human red blood cell surface which are important determinants of blood type and are targets for autoimmune or alloimmune diseases which destroy red blood cells. The Kell antigens are K, k, Kpa, Kpb, Jsa and Jsb. The Kell antigens are peptides found within the Kell protein, a 93-kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3.

<span class="mw-page-title-main">HEXB</span> Protein-coding gene in the species Homo sapiens

Beta-hexosaminidase subunit beta is an enzyme that in humans is encoded by the HEXB gene.

The Lewis antigen system is a human blood group system. It is based upon two genes on chromosome 19: FUT3, or Lewis gene; and FUT2, or Secretor gene. Both genes are expressed in glandular epithelia. FUT2 has a dominant allele which codes for an enzyme and a recessive allele which does not produce a functional enzyme. Similarly, FUT3 has a functional dominant allele (Le) and a non-functional recessive allele (le).

<span class="mw-page-title-main">HEXA</span> Protein-coding gene in the species Homo sapiens

Hexosaminidase A (alpha polypeptide), also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene, located on the 15th chromosome.

In enzymology, a glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Fucosyltransferase 3</span> Protein and coding gene in humans

Galactoside 3(4)-L-fucosyltransferase is an enzyme that in humans is encoded by the FUT3 gene.

<span class="mw-page-title-main">GYPB</span> Protein-coding gene in the species Homo sapiens

Glycophorin B (MNS blood group) (gene designation GYPB) also known as sialoglycoprotein delta and SS-active sialoglycoprotein is a protein which in humans is encoded by the GYPB gene. GYPB has also recently been designated CD235b (cluster of differentiation 235b).

<span class="mw-page-title-main">FUT2</span> Protein and coding gene in humans

Galactoside 2-alpha-L-fucosyltransferase 2 is an enzyme that in humans is encoded by the FUT2 gene. It affects the secretor status of ABO antigens.

<span class="mw-page-title-main">GALNT3</span> Protein-coding gene in the species Homo sapiens

Polypeptide N-acetylgalactosaminyltransferase 3 is an enzyme that in humans is encoded by the GALNT3 gene.

<span class="mw-page-title-main">Mucin 7</span> Protein-coding gene in the species Homo sapiens

Mucin-7 is a protein that in humans is encoded by the MUC7 gene. In animals, the MUC7 gene is found in most placental mammals, but not marsupials.

<span class="mw-page-title-main">GCNT2</span> Protein-coding gene in the species Homo sapiens

N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase is an enzyme that in humans is encoded by the GCNT2 gene.

<span class="mw-page-title-main">B4GALNT1</span> Protein-coding gene in humans

Beta-1,4 N-acetylgalactosaminyltransferase 1 is an enzyme that in humans is encoded by the B4GALNT1 gene.

<span class="mw-page-title-main">GALNT6</span> Protein-coding gene in humans

Polypeptide N-acetylgalactosaminyltransferase 6 is an enzyme that in humans is encoded by the GALNT6 gene.

<span class="mw-page-title-main">B4GALNT2</span> Protein-coding gene in the species Homo sapiens

Beta-1,4 N-acetylgalactosaminyltransferase 2 is an enzyme that in humans is encoded by the B4GALNT2 gene.

Cis AB is a type of rare mutation in the ABO gene. It happens when the transferase allele contains a mix of amino acids from either A or B alleles, producing a bifunctional enzyme that can produce both types of antigens, usually with one weaker than the other. This results in a serum test result much like the standard, separate (trans) AB phenotype, although the weaker antigen can occasionally fail to be detected. It complicates the basic inheritance pattern and blood-transfusion compatibility matching for ABO blood typing.

References

  1. 1 2 3 ENSG00000281879 GRCh38: Ensembl release 89: ENSG00000175164, ENSG00000281879 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000015787 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Ferguson-Smith MA, Aitken DA, Turleau C, de Grouchy J (September 1976). "Localisation of the human ABO: Np-1: AK-1 linkage group by regional assignment of AK-1 to 9q34". Human Genetics. 34 (1): 35–43. doi:10.1007/BF00284432. PMID   184030. S2CID   12384399.
  6. 1 2 3 "Entrez Gene: ABO ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)".
  7. ↑ "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-10-11.
  8. 1 2 Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMC   4608367 . PMID   25748612.
  9. 1 2 3 Yamamoto F, Clausen H, White T, Marken J, Hakomori S (May 1990). "Molecular genetic basis of the histo-blood group ABO system". Nature. 345 (6272): 229–33. Bibcode:1990Natur.345..229Y. doi:10.1038/345229a0. PMID   2333095. S2CID   4237562.
  10. ↑ Iwamoto S, Kumada M, Kamesaki T, Okuda H, Kajii E, Inagaki T, Saikawa D, Takeuchi K, Ohkawara S, Takahashi R, Ueda S, Inoue S, Tahara K, Hakamata Y, Kobayashi E (November 2002). "Rat encodes the paralogous gene equivalent of the human histo-blood group ABO gene. Association with antigen expression by overexpression of human ABO transferase". The Journal of Biological Chemistry. 277 (48): 46463–9. doi: 10.1074/jbc.M206439200 . PMID   12237302.
  11. ↑ "ABO - Histo-blood group ABO system transferase - Homo sapiens (Human) - ABO gene & protein". www.uniprot.org. Retrieved 2021-12-06.
  12. ↑ Seltsam A, Hallensleben M, Kollmann A, Blasczyk R (October 2003). "The nature of diversity and diversification at the ABO locus". Blood. 102 (8): 3035–42. doi: 10.1182/blood-2003-03-0955 . PMID   12829588.
  13. ↑ Ogasawara K, Bannai M, Saitou N, Yabe R, Nakata K, Takenaka M, Fujisawa K, Uchikawa M, Ishikawa Y, Juji T, Tokunaga K (June 1996). "Extensive polymorphism of ABO blood group gene: three major lineages of the alleles for the common ABO phenotypes". Human Genetics. 97 (6): 777–83. doi:10.1007/BF02346189. PMID   8641696. S2CID   12076999.
  14. ↑ Goldman M (February 2007). "Translational mini-review series on Toll-like receptors: Toll-like receptor ligands as novel pharmaceuticals for allergic disorders". Clinical and Experimental Immunology. 147 (2): 208–16. doi:10.1111/j.1365-2249.2006.03296.x. PMC   1810467 . PMID   17223960.
  15. ↑ Kay HE (November 1982). "Bone marrow transplantation: 1982". British Medical Journal. 285 (6351): 1296–8. doi:10.1136/bmj.285.6351.1296. PMC   1500229 . PMID   6812684.
  16. ↑ Hakomori S (December 1999). "Antigen structure and genetic basis of histo-blood groups A, B and O: their changes associated with human cancer". Biochimica et Biophysica Acta (BBA) - General Subjects. 1473 (1): 247–66. doi:10.1016/s0304-4165(99)00183-x. PMID   10580143.
  17. 1 2 Dabelsteen E, Gao S (January 2005). "ABO blood-group antigens in oral cancer". Journal of Dental Research. 84 (1): 21–8. doi:10.1177/154405910508400103. PMID   15615870. S2CID   16975373.
  18. ↑ Dabelsteen E (February 2002). "ABO blood group antigens in oral mucosa. What is new?". Journal of Oral Pathology & Medicine. 31 (2): 65–70. doi:10.1046/j.0904-2512.2001.00004.x. PMID   11896825.
  19. ↑ Amundadottir LT (2016-01-01). "Pancreatic Cancer Genetics". International Journal of Biological Sciences. 12 (3): 314–25. doi:10.7150/ijbs.15001. PMC   4753160 . PMID   26929738.
  20. ↑ Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, et al. (September 2009). "Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer". Nature Genetics. 41 (9): 986–90. doi:10.1038/ng.429. PMC   2839871 . PMID   19648918.

Further reading

See also

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