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MNS Blood Group System

glycophorin A/B/E
Gene locus - GYPA,GYPB,GYPE(Because of problems with nucleotide number assignments,consult the cited publication for recombination data)


Antigens are glycophorins A and B (GPA and GPB), products of two tightly linked homologous genes GYPA and GYPB of the glycophorin gene family, each present in two different allelic forms. GPA bears the epitopes for the M,N blood groups and GPB, for S,s blood groups. The M and N allelic forms are about equally distributed in world populations. GPA and GPB are type I integral membrane proteins. GPA is the major sialoglycoproteins of the erythrocyte membrane present in about one million copies per cell; it contains ~ 50% carbohydrate,clustered in its extracellular domain in form of sialylated tri- and tetrasaccharide O- glycans and a single complex biantennary N-glycan.The level of GPB at the membrane surface is one tenth less; GPB has the same disposition and pattern of glycosylation but it lacks the N- linked unit. GPE, another member of the gene family, does not appear to be expressed under normal physiological conditions; however, it participates in gene rearrangments resulting in variant alleles. Both GPB and GBE differ from GPA in that they contain pseudoexons equivalent to exons III and exon IV (GPE only) that participate in recombination events. Also, regions 3' of exon 5 differ in sequence.

The genes

The three glycophorin genes show a high degree of sequence homology and probably arose by gene duplication. Each gene is ~30 kb and they reside in a ~350 kb gene cluster (5'-GYPA-GYPB-GYPE-3') on 4q28-q31. Their high degree of sequence homology and organization along the chromosome may be responsible for the relatively frequent occurrence of unequal homologous recombinations and gene conversions among the three genes.(Because of problems with nucleotide numerical assignments, please consult the cited publication for details of recombination) A number of the resulting glycophorin products show variant blood group phenotypes, whose molecular studies, in turn, led to the documentation of those gene rearrangements.

The GYPA gene family is one of the very few among human gene families in which the expression of a large number of alleles results in immunogenic antigens. Thus, its diversity level is unusually high (McBean et al. Transfusion 2014 online Dec.19)

Function of proteins

The function of GPA and GPB is not yet clear. However the absence of GPA and/or GPB from erythrocytes, as documented in certain variant erythrocytes in homozygous states (Mk, En(a), S-s-) does not result in significant physiological abnormalities. Possibly, as membrane abundantly glycosylated glycoproteins they provide a glycan coat to the erythrocyte; they serve as receptors for complement, cytokines, bacteria, viruses, P. falciparum; they may participate in regulation of the integrity of the membrane by association with cytoskeleton proteins. A role in Band 3 function is suggested by the absence of GPA in erythrocyte membranes from mice in which band 3 gene (SLC4A1) was inactivated (Hassouns H. et al., Blood, 91:2146, 1998).

Tissue distribution

Erythroid tissues exclusively

Disease association

So far, none apparent. Individuals bearing variant forms of glycophorins, including those who do not express glycophorins at the erythocyte surface appear to be physiologically sound.

Historical aspects

Variants of the MNS system were the first in which the molecular basis for blood group polymorphism was demonstrated, both at protein and gene levels (Mg and Mc in 1981, PMID 6166001; 6940143 and GYPBdel in 1987, PMID 2823938).

About the alleles

The MNS system is nearly unique (except for the Rh system) in that gene rearrangements are a prevailing mechanism for the observed DNA variation resulting in variant alleles. Names of alleles are based on serological phenotypes and on the nature of gene rearrangement, whenever it occurs. Incidence in world populations of most rare alleles is less than 1%, except GPSta (Japan: 6%), GPMiIII (over 90% in certain regions of Taiwan), GPHenshaw or deletion of GPB (high in certain Black populations). A recent study details, by genotyping, the incidence of variant alleles encoding the Miltenberger and Sta phenotypes among the Taiwanese (Shihset al. ).

In the list of alleles, the genomic or cDNA changes are numbered according to recommendations of den Dunnen and Antonarakis (Human Mutation 2000, 15:7-12) so that "A" of the first codon is number 1. In the case of introns, the first nucleotide of each intron is number 1. Note that codon 20 is the first codon expressed in the mature protein and that GYPB pseudoexon III is not expressed except in some hybrids. Thus numbering of altered residues may be awkward; see explanation included under "details" in allele designated GYPAM (reference) id331. GenBank sequences L31860 for GYPA and J02982 for GYPB are used as reference sequences.

Compilation of GYPA/B/E alleles in BGMUT. (Excel; February 2016)

Other database IDs and links

NCBI genes
2993 for GYPA
2994 for GYPB
2996 for GYPE
Uniprot ID
P02724 for GYPA
P06028 for GYPB
P15421 for GYPE
Genbank proteins
NP_002090 for GYPA
NP_002091 for GYPB
NP_002093 for GYPE
Gene nomenclature database ID
4702 for GYPA
4703 for GYPB
4705 for GYPE
Genbank nucleic acids
NM_002099 for GYPA
NM_002100 for GYPB
NM_002102 for GYPE
NCBI homologenes for homologs and orthologs NCBI dbSNP for single nucleotide polymorphisms
2993 for GYPA
2994 for GYPB
2996 for GYPE
OMIM ID - at Online Mendelian Inheritance in Man
111300 for GYPA
111740 for GYPB
138590 for GYPE


New PubMed entries with the terms MNS and blood from the last 30 days.
NCBI Book Sections with the terms MNS and blood.


Information is also available on the orthologs of MNS system genes.


Olga O. Blumenfeld, Dept. of Biochemistry, Albert Einstein College of Medicine, New York, N.Y., 10461.

Contributors for specific alleles are listed with the alleles.


Updated 2016-04-20 00:46:55.280
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