In addition to the variants of band 3 leading to abnormalities of erythrocyte shape (Liu et al., 1990), Mueller and Morrison (1977) identified a polymorphism tentatively described as an elongation of the cytoplasmic domain, whose structure was still to be defined. Ranney et al. (1990) found a silent band 3 polymorphism, called band 3 Memphis, in all human populations with a frequency varying from one population to another. Yannoukakos et al. (1991) demonstrated that this electrophoretic variant is due to substitution of glutamic acid for lysine at position 56. An A-to-G substitution in the first base of codon 56 is responsible for the change.
Ideguchi et al. (1992) showed that the prevalence of the Memphis variant is particularly high in Japanese; the calculated gene frequency was 0.156, about 4 times higher than in Caucasians. They found that the transport rate of phosphoenolpyruvate in erythrocytes of homozygotes was decreased to about 80% of that in control cells and the rate in heterozygotes was at an intermediate level. They interpreted this as indicating that some structural changes in the cytoplasmic domain of band 3 influence the conformation of the anion transport system. The band 3 Memphis variant is characterized by a reduced mobility of proteolytic fragments derived from the N-terminus of the cytoplasmic domain of band 3 (cdb3).
Jarolim et al. (1992) found the AAG-to-GAG transition at codon 56 resulting in the lys56-to-glu substitution in all of 12 heterozygotes including 1 white, 1 black, 1 Chinese, 1 Filipino, 1 Malay, and 7 Melanesian subjects. Since most of the previously cloned mouse, rat, and chicken band 3 and band 3-related proteins contain glutamic acid in the position corresponding to amino acid 56 in the human band 3, Jarolim et al. (1992) proposed that the Memphis variant is the evolutionarily older form of band 3.
The Memphis polymorphism is also referred to as rs5036. Wilder et al. (2009) found that all 4 Indonesian chromosomes with the 27-bp deletion (109270.0002) also carried the Memphis polymorphism, suggesting that it is a target of recent natural selection.