Names for MNS blood group alleles v2.0 110914

Names for MNS Blood Group Alleles

General description: The MNS blood group system consists of 46 antigens carried on A (GPA), glycophorin B (GPB) or on hybrids of these . These are single pass type I membrane glycoproteins that are heavily O-glycosylated. GPA carries an N- glycan. GPA consists of 131 amino acids, GPB of 72 amino acids and both have a leader sequence of 19 amino acids that is cleaved from the membrane bound . The hybrid proteins vary in length based on their composition but also have a 19 amino acid leader sequence. GPA is encoded by GYPA, GPB by GYPB. A third in this family, GYPE, normally does not encode detectable protein at the red cell surface but the gene has been shown to be involved in some gene rearrangements that encode cell-surface borne hybrid proteins. As described above, the proteins are encoded by GYPA or GYPB, or MNS if analysis is to predict a blood group antigen.

Gene name: GYPA GYPB GYPE Number of 7 5 plus 1 pseudoexon 4 plus 2 exons: pseudoexons Initiation Exon 2 Exon 2 Exon 2 codon: Stop codon: Exon 7 Exon 6‡ Exon 6‡ GenBank #: NM_002099 NM_002100 NM_002102 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 pseudoexon is involved in many gene rearrangements encoding hybrid glycophorins in this blood group system. Similarly, GYPE pseudoexons 3 and 4 correspond to GYPA exon 3 and 4 sequences. These GYPE pseudoexons are involved in gene rearrangements encoding hybrids.

Reference allele for GYPA: Accession number: L31860 Preferred: GYPA*01 Acceptable: GYPA*01, GYPA*M or M if inferred by hemagglutination Reference allele for GYPB: Accession number: J02982 Preferred: GYPB*04 Acceptable: GYPB*04, GYPB*s or s if inferred by hemagglutination

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Table 1. MNS alleles with single nucleotide polymorphisms that generate blood group antigens. A. GYPA: Reference allele MNS*01 encodes M, Ena, 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/ Amino acid change Comments Exon GYPA*01 MNS:1 or M+ GYPA*M 59C; 71G; 72T 2 Ser20, Gly24 MNS:2 GYPA*02 N+ GYPA*N 59C>T; 71G>A; 72T>G 2 Ser20Leu, Gly24Glu MNS:1,-2,8† GYPA*08 71G>A,72T>G 2 Mc+ GYP.Mc Gly24Glu MNS:7,9,–40 GYPA*09 Vw+ GYPA*Vw 140C>T 3 Thr47Met MNS:-1,-2,11 GYPA*11 68C>A 2 Thr23Asn Mg+ GYPA*Mg MNS:12 GYPA*12 Vr+ GYPA*Vr 197C>A 3 Ser66Tyr MNS:14 GYPA*14 Mt(a+) GYPA*Mta 230C>T 3 Thr77Ile MNS:16 GYPA*16 Ri(a+); GYPA*Ria 226G>A 3 Glu76Lys MNS:18 Ny(a+) GYPA*18 138T>A 3 Gln46Glu MNS:7,19,–40 GYPA*19 Hut+ GYPA*Hut 140C>A 3 Thr47Lys MNS:31 GYPA*31 Or+ GYPA*Or 148C>T 3 Arg50Trp MNS:37 GYPA*37 See alsoGYP.EBH in hybrid table ERIK+ GYPA*ERIK 232G>A 4 Gly78Arg MNS:38 GYPA*38 217C>T 3 Pro73Ser

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Phenotype Allele name Nucleotide change Intron/ Amino acid change Comments Exon Os(a+) GYPA*Osa MNS:–39,41 GYPA*41 HAG+ GYPA*HAG 250G>C 4 Ala84Pro MNS:–42,43 GYPA*43 MARS+ GYPA*MARS 244C>A 4 Glu82Lys MNS:–45 ENEV– GYPA*–45 242T>G 4 Val81Gly MNS:46 GYPA*46 MNTD+ GYPA*MNTD 107C>G 3 Thr36Arg

† Most anti-M but only few anti-N react with Mc+ RBCs

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Table 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 Nucleotide Intron/ Amino acid change Comments change Exon MNS:4 GYPB*04 s+ GYPB*s MNS :3 GYPB*03 S+ GYPB*S 143C>T 4 Thr48Met MNS:6 GYPB*06.01 59T>G, s+, He+ 60A>G, 67A>T, Leu20Trp, Thr23Ser, 71A>G, 72G>T 2 Glu24Gly; MNS:3,6 GYPB*06.02 59T>G, S+, He+ 60A>G, 67A>T, 71A>G, 72G>T, Leu20Trp, Thr23Ser, 143C>T 2 Glu24Gly; Thr48Met MNS:21 Mv+ GYPB*21 65C>G 2 Thr22Ser MNS:24 Mit+ GYPB*24 161G>A 4 Arg54His MNS:23 SD+ GYPB*23 173C>G 4 Pro58Arg MNS:–3,5W GYPB*03N.01 143C>T 4 Thr48Met, Ser84Thr S–U+w GYPB.NY 208G>T; 4 230C>T; 4 251C>G; 4 MNS:–3,5W GYPB*03N.02 59T>G; 2 Leu20Trp, S–U+w GYP.He(NY) 60A>G; 2 67A>T; 2 Thr23Ser, 71A>G; 2 Glu24Gly,

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Phenotype Allele name Nucleotide Intron/ Amino acid change Comments change Exon 72G>T; 2 143C>T; 4 Thr48Met, 208G>T; 5 Ser84Thr 230C>T; 5 251C>G 5 MNS:–3,5W GYPB*03N.03 143C>T; 4 Thr48Met S–U+w GYPB.P2 Intron 5+5g>t MNS:–3,5W GYPB*03N.04 59T>G; ;2 Leu20Trp, Thr23Ser, S–U+w GYP.He(P2) 60A>G; 2 Glu24Gly, Thr48Met 67A>T; 2 71A>G; 2 72G>T; 2 143C>T 4; Intron 5 +5g>t

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Table 2. MNS alleles created by gene rearrangement events within the GYPA gene family A: parent allele GYPA. Phenotype Allele name Nucleotide Protein Comments GYP(A-A) hybrid series MNS:15 GYP*101.01 GYPA del exon 3 GPA del46-77 GYP(A1-2-BΨ3-A4-7) St(a+), GYP.Zan MNS:15 GYP*101.02 GYPA 232G>A del exon 3 GPA del46-77 Nucleotide change at 232 destabilises St(a+) GYP.EBH normal splicing. Sta is encoded by a GYPA transcript that lacks exon 3. Full-length transcript encodes ERIK (MNS37; see table 1). MNS:15 GYP*101.03 GYPA del exon 3 GPA del46-77 GYP(A1-2-EΨ3-A4-7) St(a+) GYP.Mar MNS:6,15 GYP*101.04 GYPA 58G>T, 67A>T GPA Gly20Trp, Thr23Ser GYP(A1-2-BΨ3-A4-7) He+, St(a+) GYP.Cal GPA del 46-77 GYP(A-B) series MNS:- GYP*201.01 GYP(A1-232–B233-312) GP(A1-77-B78-104) 3,4,20,34 GYP.Hil S-s+, Hil+, MINY+ MNS:3,- GYP*202.01 GYP(A1-232–B233-312) GP(A1-77-B78-104) 4,32,33 GYP.JL 239C>T Thr80Met S+s-, TSEN+, MINY+ MNS:-1,2,-3,- GYP*203.01 GYP(A1-271–B272-369) GYPA(1-90-B91-123) breakpoint in intron 4 not defined 4,-5,36 GYP.SAT 59C>T; 71G>A; 72T>G Ser20Leu, Gly24Glu Previously GYP.TK M-N+S-s-U-, SAT+ GYP(A-B-A) series

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Phenotype Allele name Nucleotide Protein Comments GYP.Vw Numbers have not been assigned to these GYP.Hut alleles in this series and they are included in table 1. It has been proposed that they are GYP.Mc derived from hybrid but the crossover GYP.Mg points have not been determined experimentally. MNS:10,32 GYP*301.01 GYP(A1-159–BΨ160- GP(A1-52-B53-58-A59-149); Also expresses Mur antigen Mur +, Dane+ GYP.Dane 177–A178-450); 191T>A Ile46Asn MNS:10,32,– GYP*301.02 GYP(A1-159–BΨ160- GP(A1-52-B53-58-A59-149) Also expresses Mur antigen; does not 44 GYP.Dane 177–A178-450) express ENDA Mur +, Dane+, ENDA– MNS:26, 27 GYP*302.01 GYP(A1-202–BΨ203– GPA(1-67)-B(68)-GPA(69-150) Gene conversion in exon 3 replaces GYPA Hop+,Nob+ GYP.Joh A204-450) Arg68Thr nucleotide 203 with the corresponding nucleotide from GYPBΨ3. This is the minimum but the breakpoint is not defined. MNS:–26,27 GYP*302.02 GYP(A1-202–BΨ203- GPA(1-67)-B(68-72)-GPA(73-150) Gene conversion in exon 3 replaces GYPA Hop–,Nob+ GYP.Nob 212–A213-450) Arg68Thr; Tyr71Ser nucleotides (203-212) with corresponding 203G>C; 212A>C nucleotides from GYPBΨ3. This is the minimum but the breakpoint is not defined. MNS:20, –34 GYP*303 GYP(A1-238–B239-242– GPA(1-79)-B(80-81)-GPA(82-150) Gene conversion in exon 4 replaces GYPA Hil+, MINY– GYP.KI A243-450) Arg80Thr;Val81Gly nucleotides (239-242) with corresponding 239G>C; 242T>G nucleotides from GYPB. This is the minimum but the breakpoint is not defined.

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Table 2. MNS alleles created by gene rearrangement events within the GYPA gene family: B: parent allele GYPB Phenotype Allele name Nucleotide Amino acid Comments GYP(B-A) hybrid series MNS:15 GYP*401 GYP(B1-136-A137-354) GPB(1-46)-A(47-118) Reciprocal product is GYP.Hil St(a+) GYP.Sch MNS:–3,4,24 GYP.402 GYP(B1-175-A176-354) GPB(1-58)-A(59-118) Reciprocal product is GYP.Tk Dantu+ GYP.Dantu GYP(B-A-B) hybrid series MNS:– GYP.501 GYP(B1-136-Bψ137-204- GP(B1-69-A70-77- Novel sequence derived from composite exon; 3,4,8,10,20,34 GYP.Mur A205-229-B230-366) B78-122) GYPB 5' pseudoexon 3 + GYPA 3' exon 3 s ,35 GPB ins 46-77 S–s+, Mi(a+), DKHKRDTYPAHTAN Mur+, Hil+, EVSEISVRTVYPPEE MUT+, MINY+ ET MNS:3,– GYP.502 GYP(B1-136-Bψ137-204- GP(B1-69-A70-77- Novel sequence derived from composite exon; 4,8,10,26,33,3 GYP.Hop A205-229-B230-366) B78-122) GYPB 5' pseudoexon 3 + GYPA 3' exon 3 4,35 236C>G GPBS ins 46-77 S+s–, Mi(a+), DKHKRDTYPAHTAN Mur+, Hop+, EVSEISVRTVYPPEE TSEN+, ET MUT+, MINY+ Thr80Met MNS:– GYP.503 GYP(B1-136-Bψ137-210- GP(B1-71-A72-77- Novel sequence derived from composite exon; 3,4,8,10,20,26 GYP.Bun A211-229-B230-366) B78-122) GYPB 5' pseudoexon 3 + GYPA 3' exon 3 s 34,35 GPB ins 46-77 S–s+, Mi(a+), DKHKRDTYPAHTAN Mur+, Hil+, EVSEISVRTVYPPEE MUT+, MINY+ ET MNS:–3,4,8, GYP.504 GYP(B1-136-Bψ137-159- GP(B1-53-A54-78- Novel sequence derived from composite exon; 20,34,35 GYP.HF A160-232-B233-369) B79-123) GYPB 5' pseudoexon 3 + GYPA 3' exon 3 s S–s+, Mi(a+), in GPB

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Phenotype Allele name Nucleotide Amino acid Comments Hil+, MUT+, DKHKRDTYAATPRA MINY+ HEVSEISVRTVYPPE EET46-77ins MNS: etc GYP*505 He+ GYP.He(GL)

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Phenotype Allele name Nucleotide Amino acid Comments GYP deletion hybrids MNS:–1,–2 GYPA*01N Del GYPA exons 2-7 : GPA absent En(a–) GYPB exon 1 M –N– MNS:–3,–4,–5 GYPB*01N Del GYPB exons 2-5 ; GPB absent S–s–U– GYPE exon 1 MNS:–1,–2,– GYP*01N Del GYPA exons 2-7 ; GPA and GPB 3,–4,–5 GYPB exons 1-5 absent MkMk M –N–S–s–

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