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Gene Review

GYPA  -  glycophorin A (MNS blood group)

Homo sapiens

Synonyms: CD235a, GPA, GPErik, GPSAT, Glycophorin-A, ...
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Disease relevance of GYPA

  • Association of blood groups with essential and secondary hypertension. A possible association of the MNS system [1].
  • To determine which polyadenylation signals are utilized, cDNA clones encoding GPA were isolated from a cDNA library of human erythroleukemia cell line K562 and the 3'-regions of the cDNAs were specifically amplified by the polymerase chain reaction [2].
  • The minor, although highly significant, changes which were recognized in the PAS pattern of beta-thalassemia patients compared with normal controls concerned the PAS-4 region and a shoulder trailing band PAS-2, which both increased in staining intensity relatively to the main sialocomponent PAS-1 [3].
  • The isolated vesicles maintain their cytoplasmic integrity and normal membrane orientation, and are resistant to hemolysis over the pH range 5.0 - 11.0 and temperature range 4-50 degrees C. The only membrane proteins detected in vesicles from human erythrocytes were band 3 region polypeptides and bands PAS-1, PAS-2 and PAS-3 [4].
  • Tn and MN glycoproteins were equally potent inhibitors of influenza virus HA [5].

Psychiatry related information on GYPA

  • The best predictors for GPA were academic self-efficacy and achievement motivation (ps =.496 and.303, respectively) [6].
  • Serial samples from 40 heavy smokers ( > or = pack/day for > or = 1 year) enrolled in a smoking cessation program were assayed for cotinine, polycyclic aromatic hydrocarbon (PAH)-DNA, 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts, and glycophorin A (GPA) mutations [7].
  • Depression, self-esteem, suicide ideation, death anxiety, and GPA in high school students of divorced and nondivorced parents [8].
  • Negative correlations among scores on competitiveness, GPA, and scores on internal locus of control were significant [9].
  • An ethnically diverse group of college students reported their GPA and responded to the Parenting Style Index [10].

High impact information on GYPA

  • Using antibodies directed against different structural regions of the major sialoglycoprotein alpha, we confirm here and two variant erythrocytes (Miltenberger class V (MiV) and Ph) contain hybrid sialoglycoprotein molecules (Fig. 1). These hybrid sialoglycoproteins arise from cross-over events between the genes coding for alpha and delta [11].
  • The spontaneous and induced VFs agree with previous measurements of radiation-induced mutagenesis in other systems; this evidence supports a mutational origin for variant cells characterized by a loss of GPA expression and suggests that the GPA assay system may provide a cumulative dosimeter of past radiation exposures [12].
  • Like the early blood-group markers (e.g., Rh and MNS), tightly linked biallelic SNPs can be combined into composite markers with heterozygosity similar to that of short-tandem-repeat polymorphisms [13].
  • Thus, these results suggest that benzene produces gene-duplicating mutations but does not produce gene-inactivating mutations at the GPA locus in bone marrow cells of humans exposed to high benzene levels [14].
  • NN variants result from loss of the GPA M allele and duplication of the N allele, presumably through recombination mechanisms, whereas NO variants arise from gene inactivation, presumably due to point mutations and deletions [14].

Chemical compound and disease context of GYPA


Biological context of GYPA

  • CONCLUSIONS: The GP.Hop phenotype is produced by a hybrid GP(B-A-B) protein caused by a DNA insertion of GYPA into GYPB [16].
  • PCR-amplified products of the coding exons of GYPA were studied by single-strand conformation polymorphism analysis, and exon 3 was sequenced [17].
  • Those restriction fragments characteristic of the GPA 3' and GPB 5' ends were absent from the SAT homozygote and showed reduced intensity in SAT heterozygotes [18].
  • The low-frequency MNS blood group antigens Ny(a) (MNS18) and Os(a) (MNS38) are associated with GPA amino acid substitutions [17].
  • These results provide further insight into the model for evolution of the GPA gene family, indicating that the mechanisms underlying inter- and intraspecific polymorphism of glycophorins could predate the divergence of gorillas as the consequence of gene duplication and diversification [19].

Anatomical context of GYPA


Associations of GYPA with chemical compounds

  • The coexpression of GPA with band 3 increased stilbene disulfonate-sensitive chloride transport into the oocytes [23].
  • The present study also revealed that this Sta individual has a variant GPA gene; substitution of adenine for guanine at the nucleotide for codon 39 results in substitution of lysine for arginine at amino acid 39, and loss of an SstI restriction site [24].
  • The GPA-deficient cells had a normal K(d) for iodide binding, in agreement with the unchanged K(m) found in transport studies [25].
  • The co-expression of GPA with either glycosylated or unglycosylated b3 increased the stilbene disulphonate-sensitive chloride transport into oocytes at low cRNA concentrations [26].
  • V glycoprotein (donor F. M.) contains approximately 60 amino acid residues of GPA at its N-terminus [27].

Physical interactions of GYPA


Regulatory relationships of GYPA

  • Glycophorins A (GPA) and B (GPB) are specifically expressed in human erythrocytes and express MN and Ss blood group antigens [2].

Other interactions of GYPA

  • GPA transcripts were very stable (at least 24 h), whereas GPB transcripts were severely reduced after 17 h [20].
  • STUDY DESIGN AND METHODS: Taking advantage of the differences between the GPA and GPB genes, a polymerase chain reaction-based method was developed to detect all the Miltenberger glycophorin variants and St(a) subtype [29].
  • BACKGROUND: The GP.Hop (Mi.IV) phenotype expresses the MNS low-incidence antigens Mur, Hop, TSEN, MINY, and MUT [16].
  • Population data were generated for the loci LDLR, GYPA, HBGG, D7S8, Gc, HLA-DQA1, and D1S80 from 180 Arabs from Dubai [30].
  • The dendrograms based on six coding loci (HLDQA1, LDLR, GYPA, HBGG, D7S8, GC) differs from those based on STR and VNTR markers [31].

Analytical, diagnostic and therapeutic context of GYPA

  • MATERIALS AND METHODS: Following RT-PCR amplification of total RNA isolated from one Vr+ person (G488) and one Mt(a+) person (GH), the genes encoding glycophorin A (GYPA) and glycophorin B (GYPB) were cloned and sequenced [32].
  • Immunoblotting with anti-Os(a) and an MAIEA assay with MoAbs to GPA showed that Os(a) is on GPA [17].
  • Distribution of alleles of three tetrameric STR loci HUMHPRTB, HUMF13B, HUMLPL and other six PCR based loci HLA DQA1, LDLR, GYPA, HBGG, D7S8, Gc in eight predominant populations of India [33].
  • Japanese population DNA typing data for the loci LDLR, GYPA, HBGG, D7S8, and GC [34].
  • The effects of blood transfusions on PCR DNA typing at the CSF1P0, TP0X, TH01, D1S80, HLA-DQA1, LDLR, GYPA, HBGG, D7S8 and GC loci [35].


  1. Association of blood groups with essential and secondary hypertension. A possible association of the MNS system. Miller, J.Z., Grim, C.E., Conneally, P.M., Weinberger, M.H. Hypertension (1979) [Pubmed]
  2. Characterization of glycophorin A transcripts: control by the common erythroid-specific promoter and alternative usage of different polyadenylation signals. Kudo, S., Onda, M., Fukuda, M. J. Biochem. (1994) [Pubmed]
  3. Minor changes in the sodium dodecyl sulphate-gel electrophoresis periodic acid-Schiff-staining profiles of erythrocyte membranes in beta-thalassemia major. Calatroni, A., Barberi, I., Salpietro, C. Ital. J. Biochem. (1979) [Pubmed]
  4. Isolation and characterization of large (0.5 - 1.0 micron) cytoskeleton-free vesicles from human and rabbit erythrocytes. Leonards, K.S., Ohki, S. Biochim. Biophys. Acta (1983) [Pubmed]
  5. Immunochemical studies on Tn erythrocyte glycoprotein. Lee, L.T., Frank, S., de Jongh, D.S., Howe, C. Blood (1981) [Pubmed]
  6. Do psychosocial and study skill factors predict college outcomes? A meta-analysis. Robbins, S.B., Lauver, K., Le, H., Davis, D., Langley, R., Carlstrom, A. Psychological bulletin. (2004) [Pubmed]
  7. Decline of DNA damage and other biomarkers in peripheral blood following smoking cessation. Mooney, L.A., Santella, R.M., Covey, L., Jeffrey, A.M., Bigbee, W., Randall, M.C., Cooper, T.B., Ottman, R., Tsai, W.Y., Wazneh, L. Cancer Epidemiol. Biomarkers Prev. (1995) [Pubmed]
  8. Depression, self-esteem, suicide ideation, death anxiety, and GPA in high school students of divorced and nondivorced parents. Brubeck, D., Beer, J. Psychological reports. (1992) [Pubmed]
  9. Competitiveness: relations with GPA, locus of control, sex, and athletic status. Frederick, C.M. Perceptual and motor skills. (2000) [Pubmed]
  10. Parenting styles and academic achievement in college students. Joshi, A., Ferris, J.C., Otto, A.L., Regan, P.C. Psychological reports. (2003) [Pubmed]
  11. Immunochemical evidence for hybrid sialoglycoproteins of human erythrocytes. Mawby, W.J., Anstee, D.J., Tanner, M.J. Nature (1981) [Pubmed]
  12. Evidence for increased somatic cell mutations at the glycophorin A locus in atomic bomb survivors. Langlois, R.G., Bigbee, W.L., Kyoizumi, S., Nakamura, N., Bean, M.A., Akiyama, M., Jensen, R.H. Science (1987) [Pubmed]
  13. Equivalence of single- and multilocus markers: power to detect linkage with composite markers derived from biallelic loci. Wilson, A.F., Sorant, A.J. Am. J. Hum. Genet. (2000) [Pubmed]
  14. Benzene induces gene-duplicating but not gene-inactivating mutations at the glycophorin A locus in exposed humans. Rothman, N., Haas, R., Hayes, R.B., Li, G.L., Wiemels, J., Campleman, S., Quintana, P.J., Xi, L.J., Dosemeci, M., Titenko-Holland, N. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  15. Beta-glycosidases and diabetic microangiopathy. I. Decreases of beta-glycosidase activities in diabetic rat kidney. Fushimi, H., Tarui, S. J. Biochem. (1976) [Pubmed]
  16. Identification of a novel hybrid glycophorin gene encoding GP.Hop. Storry, J.R., Poole, J., Condon, J., Reid, M.E. Transfusion (2000) [Pubmed]
  17. The low-frequency MNS blood group antigens Ny(a) (MNS18) and Os(a) (MNS38) are associated with GPA amino acid substitutions. Daniels, G.L., Bruce, L.J., Mawby, W.J., Green, C.A., Petty, A., Okubo, Y., Kornstad, L., Tanner, M.J. Transfusion (2000) [Pubmed]
  18. Glycophorin SAT of the human erythrocyte membrane is specified by a hybrid gene reciprocal to glycophorin Dantu gene. Huang, C.H., Reid, M.E., Okubo, Y., Daniels, G.L., Blumenfeld, O.O. Blood (1995) [Pubmed]
  19. The glycophorin A gene family in gorillas: structure, expression, and comparison with the human and chimpanzee homologues. Xie, S.S., Huang, C.H., Reid, M.E., Blancher, A., Blumenfeld, O.O. Biochem. Genet. (1997) [Pubmed]
  20. Post-transcriptional regulation of the cell surface expression of glycophorins A, B, and E. Rahuel, C., Elouet, J.F., Cartron, J.P. J. Biol. Chem. (1994) [Pubmed]
  21. Evidence for ineffective erythropoiesis in severe sickle cell disease. Wu, C.J., Krishnamurti, L., Kutok, J.L., Biernacki, M., Rogers, S., Zhang, W., Antin, J.H., Ritz, J. Blood (2005) [Pubmed]
  22. Distinct regions of human glycophorin A enhance human red cell anion exchanger (band 3; AE1) transport function and surface trafficking. Young, M.T., Tanner, M.J. J. Biol. Chem. (2003) [Pubmed]
  23. Glycophorin A facilitates the expression of human band 3-mediated anion transport in Xenopus oocytes. Groves, J.D., Tanner, M.J. J. Biol. Chem. (1992) [Pubmed]
  24. Identification of the crossing-over point of a hybrid gene encoding human glycophorin variant Sta. Similarity to the crossing-over point in haptoglobin-related genes. Rearden, A., Phan, H., Dubnicoff, T., Kudo, S., Fukuda, M. J. Biol. Chem. (1990) [Pubmed]
  25. Altered structure and anion transport properties of band 3 (AE1, SLC4A1) in human red cells lacking glycophorin A. Bruce, L.J., Pan, R.J., Cope, D.L., Uchikawa, M., Gunn, R.B., Cherry, R.J., Tanner, M.J. J. Biol. Chem. (2004) [Pubmed]
  26. Role of N-glycosylation in the expression of human band 3-mediated anion transport. Groves, J.D., Tanner, M.J. Mol. Membr. Biol. (1994) [Pubmed]
  27. Molecular analysis of glycophorin A and B gene structure and expression in homozygous Miltenberger class V (Mi. V) human erythrocytes. Vignal, A., Rahuel, C., el Maliki, B., London, J., le van Kim, C., Blanchard, D., Andre, C., d'Auriol, L., Galibert, F., Blajchman, M.A. Eur. J. Biochem. (1989) [Pubmed]
  28. Protein architecture of the erythrocyte membrane. Morrison, M., Mueller, T.J., Edwards, H.H. Prog. Clin. Biol. Res. (1981) [Pubmed]
  29. Genomic typing of human red cell miltenberger glycophorins in a Taiwanese population. Shih, M.C., Yang, L.H., Wang, N.M., Chang, J.G. Transfusion (2000) [Pubmed]
  30. Population data on the PCR-based loci LDLR GYPA, HBGG, D7S8, Gc, HLA-DQA1, and D1S80 from Arabs from Dubai. Alkhayat, A., Alshamali, F., Budowle, B. Forensic Sci. Int. (1996) [Pubmed]
  31. Genetic structure and affinity among eight ethnic populations of Eastern India: based on 22 polymorphic DNA loci. Kashyap, V.K., Chattopadhyay, P., Dutta, R., Vasulu, T.S. Am. J. Hum. Biol. (2004) [Pubmed]
  32. The MNS blood group antigens, Vr (MNS12) and Mt(a) (MNS14), each arise from an amino acid substitution on glycophorin A. Storry, J.R., Coghlan, G., Poole, J., Figueroa, D., Reid, M.E. Vox Sang. (2000) [Pubmed]
  33. Distribution of alleles of three tetrameric STR loci HUMHPRTB, HUMF13B, HUMLPL and other six PCR based loci HLA DQA1, LDLR, GYPA, HBGG, D7S8, Gc in eight predominant populations of India. Chattopadhyay, P., Kashyap, V.K. Forensic Sci. Int. (2001) [Pubmed]
  34. Japanese population DNA typing data for the loci LDLR, GYPA, HBGG, D7S8, and GC. Watanabe, Y., Yamada, S., Nagai, A., Takayama, T., Hirata, K., Bunai, Y., Ohya, I. J. Forensic Sci. (1997) [Pubmed]
  35. The effects of blood transfusions on PCR DNA typing at the CSF1P0, TP0X, TH01, D1S80, HLA-DQA1, LDLR, GYPA, HBGG, D7S8 and GC loci. Brauner, P., Shpitzen, M., Freund, M., Manny, N. J. Forensic Sci. (1997) [Pubmed]
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