Names for MNS Blood Group Alleles

Names for MNS blood group alleles v2.0 110914Names for MNS Blood Group AllelesGeneral description: The MNS blood group system consists of 46 antigens carried onglycophorin A (GPA), glycophorin B (GPB) or on hybrids of theseglycophorins. These proteins are single pass type I membraneglycoproteins that are heavily O-glycosylated. GPA carries an N-glycan. GPA consists of 131 amino acids, GPB of 72 amino acidsand both have a leader sequence of 19 amino acids that is cleavedfrom the membrane bound protein. The hybrid proteins vary inlength based on their composition but also have a 19 amino acidleader sequence. GPA is encoded by GYPA, GPB by GYPB. Athird gene in this family, GYPE, normally does not encodedetectable protein at the red cell surface but the gene has beenshown to be involved in some gene rearrangements that encodecell-surface borne hybrid proteins. As described above, theproteins are encoded by GYPA or GYPB, or MNS if analysis is topredict a blood group antigen.Gene name: GYPA GYPB GYPENumber ofexons:7 5 plus 1 pseudoexon 4 plus 2pseudoexonsInitiation Exon 2 Exon 2 Exon 2codon:Stop codon: Exon 7 Exon 6‡ Exon 6‡GenBank #: NM_002099 NM_002100 NM_002102Entrez GeneID: 2993 2994 2996‡ Exon numbering accounts for the presence of pseudoexons in GYPB and GYPE. Thus,GYPB pseudoexon 3 corresponds to the GYPA exon 3 sequence. This GYPB pseudoexonis involved in many gene rearrangements encoding hybrid glycophorins in this bloodgroup system. Similarly, GYPE pseudoexons 3 and 4 correspond to GYPA exon 3 and 4sequences. These GYPE pseudoexons are involved in gene rearrangements encodinghybrids.Reference allele for GYPA:Accession number:Preferred:Acceptable:Reference allele for GYPB:Accession number:Preferred:Acceptable:L31860GYPA*01GYPA*01, GYPA*M or M if inferred by hemagglutinationJ02982GYPB*04GYPB*04, GYPB*s or s if inferred by hemagglutinationPage 1 of 10

Names for MNS blood group alleles v2.0 110914Table 1. MNS alleles with single nucleotide polymorphisms that generate blood group antigens.A. GYPA: Reference allele MNS*01 encodes M, En a , ENEH, ENEP, ENAV, ENDA, ENEV.Note: In most cases, the nucleotide changes also can occur on an N allele; these nucleotide changes are not given.Phenotype Allele name Nucleotide change Intron/ExonMNS:1 or M+MNS:2N+MNS:1,-2,8†M c +MNS:7,9,–40Vw+MNS:-1,-2,11M g +MNS:12Vr+MNS:14Mt(a+)MNS:16Ri(a+);GYPA*01Amino acid changeGYPA*M 59C; 71G; 72T 2 Ser20, Gly24GYPA*02GYPA*N 59C>T; 71G>A; 72T>G 2 Ser20Leu, Gly24GluGYPA*08GYP.Mc71G>A,72T>G 2Gly24GluGYPA*09GYPA*Vw 140C>T 3 Thr47MetGYPA*11GYPA*Mg68C>A 2 Thr23AsnGYPA*12GYPA*Vr 197C>A 3 Ser66TyrGYPA*14GYPA*Mta 230C>T 3 Thr77IleGYPA*16GYPA*Ria 226G>A 3 Glu76LysMNS:18Ny(a+) GYPA*18 138T>A 3 Gln46GluMNS:7,19,–40Hut+MNS:31Or+MNS:37ERIK+GYPA*19GYPA*Hut 140C>A 3 Thr47LysGYPA*31GYPA*Or 148C>T 3 Arg50TrpGYPA*37GYPA*ERIK 232G>A 4 Gly78ArgMNS:38 GYPA*38 217C>T 3 Pro73SerCommentsSee alsoGYP.EBH in hybrid tablePage 2 of 10

Names for MNS blood group alleles v2.0 110914Phenotype Allele name Nucleotide change Intron/ExonOs(a+)GYPA*OsaMNS:–39,41HAG+MNS:–42,43MARS+GYPA*41GYPA*HAG 250G>C 4 Ala84ProGYPA*43GYPA*MARS 244C>A 4 Glu82LysMNS:–45ENEV– GYPA*–45 242T>G 4 Val81GlyMNS:46MNTD+GYPA*46GYPA*MNTD 107C>G 3 Thr36ArgAmino acid changeComments† Most anti-M but only few anti-N react with M c + RBCsPage 3 of 10

Names for MNS blood group alleles v2.0 110914Table 1. MNS alleles with single nucleotide polymorphisms that generate blood group antigens.B. GYPB: Reference allele GYPB*04 encodes ‘N’, s. Expression of the U antigen involves GPB and another protein, probably RhAG.Phenotype Allele name NucleotidechangeMNS:4s+MNS :3S+MNS:6s+, He+MNS:3,6S+, He+GYPB*04GYPB*sIntron/ExonGYPB*03GYPB*S 143C>T 4 Thr48MetGYPB*06.01GYPB*06.0259T>G,60A>G,67A>T,71A>G, 72G>T 259T>G,60A>G,67A>T,71A>G,72G>T,143C>T 2MNS:21M v + GYPB*21 65C>G 2 Thr22SerMNS:24Mit+ GYPB*24 161G>A 4 Arg54HisMNS:23S D + GYPB*23 173C>G 4 Pro58ArgMNS:–3,5WS–U+ wMNS:–3,5WS–U+ wGYPB*03N.01GYPB.NYGYPB*03N.02GYP.He(NY)143C>T208G>T;230C>T;251C>G;59T>G;60A>G;67A>T;71A>G;44442222Amino acid changeLeu20Trp, Thr23Ser,Glu24Gly;Leu20Trp, Thr23Ser,Glu24Gly; Thr48MetThr48Met, Ser84ThrLeu20Trp,Thr23Ser,Glu24Gly,CommentsPage 4 of 10

Names for MNS blood group alleles v2.0 110914Phenotype Allele name NucleotidechangeMNS:–3,5WS–U+ wMNS:–3,5WS–U+ wGYPB*03N.03GYPB.P2GYPB*03N.04GYP.He(P2)72G>T;143C>T;208G>T;230C>T;251C>GIntron/Exon24555143C>T; 4Intron5+5g>t59T>G;60A>G;67A>T;71A>G;72G>T;143C>T;222224; Intron5 +5g>tAmino acid changeThr48Met,Ser84ThrThr48MetLeu20Trp, Thr23Ser,Glu24Gly, Thr48MetCommentsPage 5 of 10

Names for MNS blood group alleles v2.0 110914Table 2. MNS alleles created by gene rearrangement events within the GYPA gene familyA: parent allele GYPA.Phenotype Allele name Nucleotide Protein CommentsGYP(A-A)hybrid seriesMNS:15St(a+),MNS:15St(a+)MNS:15St(a+)MNS:6,15He+, St(a+)GYP(A-B)seriesMNS:-3,4,20,34S-s+, Hil+,MINY+MNS:3,-4,32,33S+s-, TSEN+,MINY+MNS:-1,2,-3,-4,-5,36M-N+S-s-U-,SAT+GYP(A-B-A)seriesGYP*101.01GYP.ZanGYP*101.02GYP.EBHGYP*101.03GYP.MarGYP*101.04GYP.CalGYP*201.01GYP.HilGYP*202.01GYP.JLGYP*203.01GYP.SATGYPA del exon 3 GPA del46-77 GYP(A1-2-BΨ3-A4-7)GYPA 232G>A del exon 3 GPA del46-77 Nucleotide change at 232 destabilisesnormal splicing. St a is encoded by a GYPAtranscript that lacks exon 3. Full-lengthtranscript encodes ERIK (MNS37; see table1).GYPA del exon 3 GPA del46-77 GYP(A1-2-EΨ3-A4-7)GYPA 58G>T, 67A>TGPA Gly20Trp, Thr23SerGPA del 46-77GYP(A1-232–B233-312) GP(A1-77-B78-104)GYP(A1-232–B233-312)239C>TGYP(A1-271–B272-369)59C>T; 71G>A; 72T>GGP(A1-77-B78-104)Thr80MetGYPA(1-90-B91-123)Ser20Leu, Gly24GluGYP(A1-2-BΨ3-A4-7)breakpoint in intron 4 not definedPreviously GYP.TKPage 6 of 10

Names for MNS blood group alleles v2.0 110914Phenotype Allele name Nucleotide Protein CommentsMNS:10,32Mur +, Dane+MNS:10,32,–44Mur +, Dane+,ENDA–MNS:26, 27Hop+,Nob+MNS:–26,27Hop–,Nob+MNS:20, –34Hil+, MINY–GYP.Vw Numbers have not been assigned to theseGYP.Hutalleles in this series and they are included intable 1. It has been proposed that they areGYP.Mcderived from hybrid genes but the crossoverGYP.Mgpoints have not been determinedexperimentally.GYP*301.01GYP.DaneGYP*301.02GYP.DaneGYP*302.01GYP.JohGYP*302.02GYP.NobGYP*303GYP.KIGYP(A1-159–BΨ160-177–A178-450); 191T>AGYP(A1-159–BΨ160-177–A178-450)GYP(A1-202–BΨ203–A204-450)GYP(A1-202–BΨ203-212–A213-450)203G>C; 212A>CGYP(A1-238–B239-242–A243-450)239G>C; 242T>GGP(A1-52-B53-58-A59-149);Ile46AsnGP(A1-52-B53-58-A59-149)GPA(1-67)-B(68)-GPA(69-150)Arg68ThrGPA(1-67)-B(68-72)-GPA(73-150)Arg68Thr; Tyr71SerGPA(1-79)-B(80-81)-GPA(82-150)Arg80Thr;Val81GlyAlso expresses Mur antigenAlso expresses Mur antigen; does notexpress ENDAGene conversion in exon 3 replaces GYPAnucleotide 203 with the correspondingnucleotide from GYPBΨ3. This is theminimum but the breakpoint is not defined.Gene conversion in exon 3 replaces GYPAnucleotides (203-212) with correspondingnucleotides from GYPBΨ3. This is theminimum but the breakpoint is not defined.Gene conversion in exon 4 replaces GYPAnucleotides (239-242) with correspondingnucleotides from GYPB. This is the minimumbut the breakpoint is not defined.Page 7 of 10

Names for MNS blood group alleles v2.0 110914Table 2. MNS alleles created by gene rearrangement events within the GYPA gene family:B: parent allele GYPBPhenotype Allele name Nucleotide Amino acid CommentsGYP(B-A)hybrid seriesMNS:15St(a+)MNS:–3,4,24Dantu+GYP(B-A-B)hybrid seriesMNS:–3,4,8,10,20,34,35S–s+, Mi(a+),Mur+, Hil+,MUT+, MINY+MNS:3,–4,8,10,26,33,34,35S+s–, Mi(a+),Mur+, Hop+,TSEN+,MUT+, MINY+MNS:–3,4,8,10,20,2634,35S–s+, Mi(a+),Mur+, Hil+,MUT+, MINY+MNS:–3,4,8,20,34,35S–s+, Mi(a+),GYP*401GYP.SchGYP.402GYP.DantuGYP.501GYP.MurGYP.502GYP.HopGYP.503GYP.BunGYP.504GYP.HFGYP(B1-136-A137-354) GPB(1-46)-A(47-118) Reciprocal product is GYP.HilGYP(B1-175-A176-354) GPB(1-58)-A(59-118) Reciprocal product is GYP.TkGYP(B1-136-Bψ137-204-A205-229-B230-366)GYP(B1-136-Bψ137-204-A205-229-B230-366)236C>GGYP(B1-136-Bψ137-210-A211-229-B230-366)GYP(B1-136-Bψ137-159-A160-232-B233-369)GP(B1-69-A70-77-B78-122)GPB s ins 46-77DKHKRDTYPAHTANEVSEISVRTVYPPEEETGP(B1-69-A70-77-B78-122)GPB S ins 46-77DKHKRDTYPAHTANEVSEISVRTVYPPEEETThr80MetGP(B1-71-A72-77-B78-122)GPB s ins 46-77DKHKRDTYPAHTANEVSEISVRTVYPPEEETGP(B1-53-A54-78-B79-123)in GPB sNovel sequence derived from composite exon;GYPB 5' pseudoexon 3 + GYPA 3' exon 3Novel sequence derived from composite exon;GYPB 5' pseudoexon 3 + GYPA 3' exon 3Novel sequence derived from composite exon;GYPB 5' pseudoexon 3 + GYPA 3' exon 3Novel sequence derived from composite exon;GYPB 5' pseudoexon 3 + GYPA 3' exon 3Page 8 of 10

Names for MNS blood group alleles v2.0 110914Phenotype Allele name Nucleotide Amino acid CommentsHil+, MUT+,MINY+DKHKRDTYAATPRAHEVSEISVRTVYPPEEET46-77insMNS: etcHe+GYP*505GYP.He(GL)Page 9 of 10

Names for MNS blood group alleles v2.0 110914Phenotype Allele name Nucleotide Amino acid CommentsGYP deletionhybridsMNS:–1,–2En(a–)M –N–MNS:–3,–4,–5S–s–U–MNS:–1,–2,–3,–4,–5M k M kM –N–S–s–GYPA*01N Del GYPA exons 2-7 :GYPB exon 1GYPB*01N Del GYPB exons 2-5 ;GYPE exon 1GYP*01N Del GYPA exons 2-7 ;GYPB exons 1-5GPA absentGPB absentGPA and GPBabsentPage 10 of 10