View source for ABO (gene)

{{Infobox_gene}}
'''Histo-blood group ABO system transferase''' is an [[enzyme]] with [[glycosyltransferase]] activity, which is encoded by the ''ABO'' [[gene]] in humans.<ref name="pmid184030">{{cite journal | vauthors = Ferguson-Smith MA, Aitken DA, Turleau C, de Grouchy J | title = Localisation of the human ABO: Np-1: AK-1 linkage group by regional assignment of AK-1 to 9q34 | journal = Human Genetics | volume = 34 | issue = 1 | pages = 35–43 | date = September 1976 | pmid = 184030 | pmc =  | doi = 10.1007/BF00284432 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ABO ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=28| accessdate = }}</ref> It is ubiquitously expressed in many tissues and cell types.<ref>{{Cite web|url=http://biogps.org/#goto=genereport&id=28|title=BioGPS - your Gene Portal System|website=biogps.org|access-date=2016-10-11}}</ref> ABO determines the [[ABO blood group system|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]].<ref name="Mega_2015">{{cite journal | vauthors = 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 | title = Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials | journal = Lancet | volume = 385 | issue = 9984 | pages = 2264–71 | date = June 2015 | pmid = 25748612 | doi = 10.1016/S0140-6736(14)61730-X | pmc=4608367}}</ref>

== Structure ==

The ''ABO'' gene resides on chromosome 9 at the band 9q34.2 and contains 7 [[Exon|exons]].<ref name="entrez" /> The ''ABO'' locus encodes three [[alleles]]. The A allele produces α-1,3-N-acetylgalactosamine transferase (A-transferase), which catalyzes the transfer of GalNAc [[residue (chemistry)|residue]]s 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 [[Uridine diphosphate|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]].<ref name="yamamoto">{{cite journal | vauthors = Yamamoto F, Clausen H, White T, Marken J, Hakomori S | title = Molecular genetic basis of the histo-blood group ABO system | journal = Nature | volume = 345 | issue = 6272 | pages = 229–33 | date = May 1990 | pmid = 2333095 | doi = 10.1038/345229a0 }}</ref> The O allele lacks both enzymatic activities because of the frame shift caused by a deletion of guanine-258 in the gene which corresponds to a region near the [[N-terminus]] of the protein.<ref name="pmid12237302">{{cite journal | vauthors = 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 | title = Rat encodes the paralogous gene equivalent of the human histo-blood group ABO gene. Association with antigen expression by overexpression of human ABO transferase | journal = The Journal of Biological Chemistry | volume = 277 | issue = 48 | pages = 46463–9 | date = November 2002 | pmid = 12237302 | doi = 10.1074/jbc.M206439200 }}</ref>This results in a frameshift and translation of an almost entirely different protein.<ref name="yamamoto" /> This [[mutation]] results in a protein 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 [[ABO blood group system#Antigens|H antigen]]. These antigens play an important role in the match of [[blood transfusion]] and [[organ transplantation]].<ref name="yamamoto" /> Other minor alleles have been found for this gene.<ref name="entrez" />
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== Common alleles ==

{{Further|ABO blood group system#Distribution and evolutionary history}}
There are six common [[allele]]s in individuals of European descent. Nearly every living human's [[phenotype]] for the ABO gene is some combination of just these six alleles:<ref>{{cite journal | vauthors = Seltsam A, Hallensleben M, Kollmann A, Blasczyk R | title = The nature of diversity and diversification at the ABO locus | journal = Blood | volume = 102 | issue = 8 | pages = 3035–42 | date = October 2003 | pmid = 12829588 | doi = 10.1182/blood-2003-03-0955 }}</ref><ref>{{cite journal | vauthors = Ogasawara K, Bannai M, Saitou N, Yabe R, Nakata K, Takenaka M, Fujisawa K, Uchikawa M, Ishikawa Y, Juji T, Tokunaga K | title = Extensive polymorphism of ABO blood group gene: three major lineages of the alleles for the common ABO phenotypes | journal = Human Genetics | volume = 97 | issue = 6 | pages = 777–83 | date = June 1996 | pmid = 8641696 | doi = 10.1007/BF02346189 }}</ref>
{{div col|colwidth=20em}}
*A
**''A101'' (A1)
**''A201'' (A2)
*B
**''B101'' (B1)
*O
**''O01'' (O1)
**''O02'' (O1v)
**''O03'' (O2)
{{Div col end}}

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.<ref>{{cite journal | vauthors = Goldman M | title = Translational mini-review series on Toll-like receptors: Toll-like receptor ligands as novel pharmaceuticals for allergic disorders | journal = Clinical and Experimental Immunology | volume = 147 | issue = 2 | pages = 208–16 | date = February 2007 | pmid = 17223960 | pmc = 1810467 | doi = 10.1111/j.1365-2249.2006.03296.x }}</ref> Using anti-GTA/GTB monoclonal antibodies, it was demonstrated that a loss of these enzymes was correlated to malignant bladder and oral epithelia.<ref>{{cite journal | vauthors = Kay HE | title = Bone marrow transplantation: 1982 | journal = British Medical Journal | volume = 285 | issue = 6351 | pages = 1296–8 | date = November 1982 | pmid = 6812684 | pmc = 1500229 | doi=10.1136/bmj.285.6351.1296}}</ref><ref>{{cite journal|authorlink1=Sen-itiroh Hakomori | vauthors = Hakomori S | title = Antigen structure and genetic basis of histo-blood groups A, B and O: their changes associated with human cancer | journal = Biochimica et Biophysica Acta | volume = 1473 | issue = 1 | pages = 247–66 | date = December 1999 | pmid = 10580143 | doi=10.1016/s0304-4165(99)00183-x}}</ref> Furthermore, the expression of ABO blood group antigens in normal human tissues is dependent 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.<ref name = "Dabelsteen_2005">{{cite journal | vauthors = Dabelsteen E, Gao S | title = ABO blood-group antigens in oral cancer | journal = Journal of Dental Research | volume = 84 | issue = 1 | pages = 21–8 | date = January 2005 | pmid = 15615870 | doi=10.1177/154405910508400103}}</ref> Several studies have observed that a relative down-regulation of GTA and GTB occurs in oral carcinomas in association with tumor development.<ref name = "Dabelsteen_2005" /><ref>{{cite journal | vauthors = Dabelsteen E | title = ABO blood group antigens in oral mucosa. What is new? | journal = Journal of Oral Pathology & Medicine | volume = 31 | issue = 2 | pages = 65–70 | date = February 2002 | pmid = 11896825 | doi=10.1046/j.0904-2512.2001.00004.x}}</ref> More recently, a genome wide association study (GWAS) has identified variants in the ABO locus associated with susceptibility to [[pancreatic cancer]].<ref>{{cite journal | vauthors = Amundadottir LT | title = Pancreatic Cancer Genetics | journal = International Journal of Biological Sciences | volume = 12 | issue = 3 | pages = 314–25 | date = 2016-01-01 | pmid = 26929738 | doi = 10.7150/ijbs.15001 | pmc=4753160}}</ref><ref name="pmid19648918">{{cite journal | vauthors = Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, Bueno-de-Mesquita HB, Gross M, Helzlsouer K, Jacobs EJ, LaCroix A, Zheng W, Albanes D, Bamlet W, Berg CD, Berrino F, Bingham S, Buring JE, Bracci PM, Canzian F, Clavel-Chapelon F, Clipp S, Cotterchio M, de Andrade M, Duell EJ, Fox JW, Gallinger S, Gaziano JM, Giovannucci EL, Goggins M, González CA, Hallmans G, Hankinson SE, Hassan M, Holly EA, Hunter DJ, Hutchinson A, Jackson R, Jacobs KB, Jenab M, Kaaks R, Klein AP, Kooperberg C, Kurtz RC, Li D, Lynch SM, Mandelson M, McWilliams RR, Mendelsohn JB, Michaud DS, Olson SH, Overvad K, Patel AV, Peeters PH, Rajkovic A, Riboli E, Risch HA, Shu XO, Thomas G, Tobias GS, Trichopoulos D, Van Den Eeden SK, Virtamo J, Wactawski-Wende J, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Chanock SJ, Hartge P, Hoover RN | display-authors = 6 | title = Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer | journal = Nature Genetics | volume = 41 | issue = 9 | pages = 986–90 | date = September 2009 | pmid = 19648918 | pmc = 2839871 | doi = 10.1038/ng.429 }}</ref>

=== Clinical marker ===
A multi-locus genetic risk score study based on a combination of 27 [[locus (genetics)|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).<ref name = "Mega_2015"/>
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== References ==
{{reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Nagai M, Davè V, Kaplan BE, Yoshida A | title = Human blood group glycosyltransferases. I. Purification of n-acetylgalactosaminyltransferase | journal = The Journal of Biological Chemistry | volume = 253 | issue = 2 | pages = 377–9 | date = January 1978 | pmid = 618875 | doi =  }}
* {{cite journal | vauthors = Takeya A, Hosomi O, Shimoda N, Yazawa S | title = Biosynthesis of the blood group P antigen-like GalNAc beta 1-->3Gal beta 1-->4GlcNAc/Glc structure: a novel N-acetylgalactosaminyltransferase in human blood plasma | journal = Journal of Biochemistry | volume = 112 | issue = 3 | pages = 389–95 | date = September 1992 | pmid = 1429528 | doi =  }}
* {{cite journal | vauthors = Kominato Y, McNeill PD, Yamamoto M, Russell M, Hakomori S, Yamamoto F | title = Animal histo-blood group ABO genes | journal = Biochemical and Biophysical Research Communications | volume = 189 | issue = 1 | pages = 154–64 | date = November 1992 | pmid = 1449469 | doi = 10.1016/0006-291X(92)91538-2 }}
* {{cite journal | vauthors = Yamamoto F, McNeill PD, Hakomori S | title = Human histo-blood group A2 transferase coded by A2 allele, one of the A subtypes, is characterized by a single base deletion in the coding sequence, which results in an additional domain at the carboxyl terminal | journal = Biochemical and Biophysical Research Communications | volume = 187 | issue = 1 | pages = 366–74 | date = August 1992 | pmid = 1520322 | doi = 10.1016/S0006-291X(05)81502-5 }}
* {{cite journal | vauthors = Clausen H, White T, Takio K, Titani K, Stroud M, Holmes E, Karkov J, Thim L, Hakomori S | title = Isolation to homogeneity and partial characterization of a histo-blood group A defined Fuc alpha 1----2Gal alpha 1----3-N-acetylgalactosaminyltransferase from human lung tissue | journal = The Journal of Biological Chemistry | volume = 265 | issue = 2 | pages = 1139–45 | date = January 1990 | pmid = 2104827 | doi =  }}
* {{cite journal | vauthors = Yamamoto F, Marken J, Tsuji T, White T, Clausen H, Hakomori S | title = Cloning and characterization of DNA complementary to human UDP-GalNAc: Fuc alpha 1----2Gal alpha 1----3GalNAc transferase (histo-blood group A transferase) mRNA | journal = The Journal of Biological Chemistry | volume = 265 | issue = 2 | pages = 1146–51 | date = January 1990 | pmid = 2104828 | doi =  }}
* {{cite journal | vauthors = Yamamoto F, Hakomori S | title = Sugar-nucleotide donor specificity of histo-blood group A and B transferases is based on amino acid substitutions | journal = The Journal of Biological Chemistry | volume = 265 | issue = 31 | pages = 19257–62 | date = November 1990 | pmid = 2121736 | doi =  }}
* {{cite journal | vauthors = Whitehead JS, Bella S, Kim YS | title = An N-acetylgalactosaminyltransferase from human blood group A plasma. II. Kinetic and physicochemical properties | journal = The Journal of Biological Chemistry | volume = 249 | issue = 11 | pages = 3448–52 | date = June 1974 | pmid = 4831223 | doi =  }}
* {{cite journal | vauthors = Whitehead JS, Bella A, Kim YS | title = An N-acetylgalactosaminyltransferase from human blood group A plasma. I. Purification and agarose binding properties | journal = The Journal of Biological Chemistry | volume = 249 | issue = 11 | pages = 442–7 | date = June 1974 | pmid = 4831233 | doi =  }}
* {{cite journal | vauthors = Kobata A, Ginsburg V | title = Uridine diphosphate-N-acetyl-D-galactosamine: D-galactose alpha-3-N-acetyl-D-galactosaminyltransferase, a product of the gene that determines blood type A in man | journal = The Journal of Biological Chemistry | volume = 245 | issue = 6 | pages = 1484–90 | date = March 1970 | pmid = 5442829 | doi =  }}
* {{cite journal | vauthors = Yoshida A, Yamaguchi H, Okubo Y | title = Genetic mechanism of cis-AB inheritance. I. A case associated with unequal chromosomal crossing over | journal = American Journal of Human Genetics | volume = 32 | issue = 3 | pages = 332–8 | date = May 1980 | pmid = 6770676 | pmc = 1686052 | doi =  }}
* {{cite journal | vauthors = Olsson ML, Thuresson B, Chester MA | title = An Ael allele-specific nucleotide insertion at the blood group ABO locus and its detection using a sequence-specific polymerase chain reaction | journal = Biochemical and Biophysical Research Communications | volume = 216 | issue = 2 | pages = 642–7 | date = November 1995 | pmid = 7488159 | doi = 10.1006/bbrc.1995.2670 }}
* {{cite journal | vauthors = Bennett EP, Steffensen R, Clausen H, Weghuis DO, van Kessel AG | title = Genomic cloning of the human histo-blood group ABO locus | journal = Biochemical and Biophysical Research Communications | volume = 206 | issue = 1 | pages = 318–25 | date = January 1995 | pmid = 7598760 | doi = 10.1006/bbrc.1995.1044 }}
* {{cite journal | vauthors = Yamamoto F, McNeill PD, Hakomori S | title = Genomic organization of human histo-blood group ABO genes | journal = Glycobiology | volume = 5 | issue = 1 | pages = 51–8 | date = February 1995 | pmid = 7772867 | doi = 10.1093/glycob/5.1.51 }}
* {{cite journal | vauthors = Bennett EP, Steffensen R, Clausen H, Weghuis DO, Geurts van Kessel A | title = Genomic cloning of the human histo-blood group ABO locus | journal = Biochemical and Biophysical Research Communications | volume = 211 | issue = 1 | pages = 347 | date = June 1995 | pmid = 7779106 | doi = 10.1006/bbrc.1995.1817 }}
* {{cite journal | vauthors = Yamamoto F, McNeill PD, Kominato Y, Yamamoto M, Hakomori S, Ishimoto S, Nishida S, Shima M, Fujimura Y | title = Molecular genetic analysis of the ABO blood group system: 2. cis-AB alleles | journal = Vox Sanguinis | volume = 64 | issue = 2 | pages = 120–3 | year = 1993 | pmid = 8456556 | doi = 10.1111/j.1423-0410.1993.tb02529.x }}
* {{cite journal | vauthors = Yamamoto F, McNeill PD, Yamamoto M, Hakomori S, Harris T | title = Molecular genetic analysis of the ABO blood group system: 3. A(X) and B(A) alleles | journal = Vox Sanguinis | volume = 64 | issue = 3 | pages = 171–4 | year = 1993 | pmid = 8484250 | doi = 10.1111/j.1423-0410.1993.tb05157.x }}
* {{cite journal | vauthors = Ogasawara K, Yabe R, Uchikawa M, Saitou N, Bannai M, Nakata K, Takenaka M, Fujisawa K, Ishikawa Y, Juji T, Tokunaga K | title = Molecular genetic analysis of variant phenotypes of the ABO blood group system | journal = Blood | volume = 88 | issue = 7 | pages = 2732–7 | date = October 1996 | pmid = 8839869 | doi =  }}
{{refend}}

==See also==
* [[RHD (gene)]]

==External links==
* {{UCSC gene info|ABO}}

{{Commons category|ABO (gene)}}
{{PDB Gallery|geneid=28}}
{{NLM content}}
{{DEFAULTSORT:Abo}}