Amino acid substitutions in human erythroid protein band 3 account for the low‐incidence antigens NFLD and BOW

Abstract

SLC4A1 codes for the low-incidence red cell antigens NFLD and BOW. In light of these findings, both antigens have been assigned to the Diego blood group system.

Substitution Glu480Lys in erythroid band 3 corresponds to the Fra blood group antigen and supports existence of the second ectoplasmic loop of band 3

“…Mutations leading to band‐3 disorders have recently been reviewed 11 . We and others have described polymorphisms in the external loops of band 3 underlying various low‐incidence blood group antigens 12‐18 . In addition to clarifying the molecular basis of multiple low‐frequency blood group antigens, these results helped to confirm the existence of the putative ectoplasmic loops of band 3 as well as to estimate the length of the first, third, fourth, and seventh loops.…”

Diego Blood Group System

“…of an association between antigen expression and a missense mutation in the band 3 gene [8,10,12,14,15,17,23,25,27,29,31,157] . In most cases at least two unrelated individuals with the low frequency antigen were shown to have the associated mutation.…”

“…BOW and NFLD represent different substitutions of Pro561, whereas Wu represents a substitution of Gly565 [15,17,25,27] . NFLD is associated with amino acid changes in the fi rst and third extracellular loops [27] . The serological associations of NFLD with BOW and Wu suggest that Ala561 is most important in determining NFLD expression.…”

Distinctive Swann Blood Group Genotypes: Molecular Investigations

“…Eleven of the 14 ‘new’ Diego system antigens are former members of the ISBT’s 700 series (Wd a [7, 8], Rb a [8], WARR [9], ELO [10, 11], Wu [11, 12], Bp a [11], Mo a [11], Hg a [11], Vg a [11], Sw a [13], BOW [11, 14, 15], NFLD [14]and Jn a [16]). One of the 14, KREP [15], is a newly described antigen of low incidence; the remaining 2, Wr a and Wr b [17], are former members of the 211 collection.…”

“…In 1994, characterization of the SLC4A1 mutation and consequent amino acid substitution in erythroid protein band 3 defining Di a [4] prompted a series of molecular investigations that have expanded the Diego blood group system dramatically [5,6]. Eleven of the 14 'new' Diego system antigens are former members of the ISBT's 700 series (Wd a [7,8], Rb a [8], WARR [9], ELO [10,11], Wu [11,12], Bp a [11], Mo a [11], Hg a [11], Vg a [11], Sw a [13], BOW [11,14,15], NFLD [14] and Jn a [16]). One of the 14, KREP [15], is a newly described antigen of low incidence; the remaining 2, Wr a and Wr b [17], are former members of the 211 collection.…”