|Blood Group Antigen Gene Mutation Database|
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Gerbich Blood Group System
Gene locus - GYPC
The antigens for the Gerbich blood group system reside on Glycophorin C (GPC) or Glycophorin D (GPD) glycoproteins. Both proteins are encoded by the same gene but arise through an alternative use of two AUG initiator codons, at positions 1 and 66 of the mRNA sequence. Thus GPD is identical to GPC except it lacks the first 21 amino terminal residues of GPC. Their sizes are 32kDa and 23 kDa respectively. Both proteins are expressed on the erythocyte surface.
Both, GPC and GPD glycophorins are type 1 membrane glycoproteins. GPC is similar to the GPA family of proteins in its diposition across the membrane and the glycosylation pattern. Its extracellular domain is heavily glycosylated and it contains a single N-linked complex unit and several O-linked glycans. GPD lacks the former unit and contains fewer O-linked units.
The GYPC gene spans 13.5 kb and is organized in 4 exons, the first three encoding the extracellular domain and the 4th, the transmembrane and cytoplasmic domains. The gene contains two identical repeats 3.4 kb in length, most likely resulting from a duplication of an ancestral domain. Rearrangements within the repeated domains may be responsible for altered foms of the gene (Colinet al.).
The Gerbich blood group system is characterized by three high incidence antigens, Ge2,Ge3, Ge4, whose absence may result in absence or reduced expression of GPC and GPD, resulting in Ge negative phenotype and four rare antigens.
Function of proteins
GPC and GPD play a role in maintenance of red cell integrity via interaction with protein 4.1. Glycans contribute to the negative charge of the red cell surface. GPC can participate in the invasion of the red cell by Plasmodium falciparum, serving asthe receptor for its PfEBP-2 (EBA-140) binding ligand (Loboet al., 2003, Maieret al., 2003).
Expressed in erythroid tissues and a wide variety of other tissues including fetal liver and renal endothelium; also, expressed in non-erythroid cell lines.
Through interactions with membrane skeleton proteins, GPC or GPD may play a role in maintenance of erythrocyte membrane shape and deformability, and in some cases (for example the Leach phenotype but not Yus) their absence may result in elliptocytosis or an abnormal shape of the red cell. Also, reduction of GPC and GPD in protein 4.1-deficient red cells can be associated with hereditary elliptocytosis. Both, GPC and GBD serve as red cell receptors for influenza A and B and are putative receptors for the merozoites of Plasmodium falciparum (Pasvolet al., 1984).
Ant-Ge2 and anti-Ge3 can cause hemolytic transfusion reaction, and the latter antibody can also cause hemolytic disease of the fetus and newborn (HDFN) (Walker and Reid Immunohematology 2010,26,60-65).
The Gerbich blood group system is characterized by three high incidence antigens. Among variant alleles, those exhibiting Ge-2, Ge-3, Ge-4 phenotypes, are defined by failure in expression of "normal" GPC and GPD at the erythrocyte surface; they result in Ge deficient phenotypes, referred to as "Yus","Ge" or/and "Leach." Erythrocytes from individuals exhibiting those phenotypes show the presence of sialoglycoproteins related immunologically to GPC and GPD, that may be altered forms of the parent molecules resulting from gene rearrangments. The other rare alleles result from mutations.
In the list of alleles of GYPC and GYPD, the sequence with acc. no. M36284 is taken as reference.
When searching for a particular allele, use "name" if DNA alteration is known or, if you wish to search by phenotype or numerical terminology or the designation used by the author, use "alias" (see "Details")
Other database IDs and links
Marion E. Reid and Christine Lomas-Francis, Immunohematology, New York Blood Center, 310 East 67 St., New York, N.Y.10021
Contributors for specific alleles are listed with the alleles.
Updated 2013-10-18 18:31:33.627