CD20, the high-affinity IgE receptor beta chain (Fc epsilon RI beta), and H
Tm4 are structurally related cell surface proteins expressed by hematopoiet
ic cells. Recently, 16 novel human and mouse genes were identified that enc
ode new members of this nascent protein family that we have named the membr
ane-spanning 4A gene family, with at least 12 subgroups (MS4A1-MS4A12). In
the current study, we identified three additional human MS4A genes: MS4A4E,
MS4A6E, and MS4A10. All family members have at least four potential transm
embrane domains and N- and C-terminal cytoplasmic domains encoded by distin
ct exons, except MS4A6E which contains two transmembrane domains. Otherwise
, the 12 currently identified MS4A genes share common structural features a
nd similar intron/exon splice boundaries, and are clustered along an simila
r to 600-kb region of Chromosome 11q12. In contrast to other MS4A genes, MS
4A4E, MS4A6E, and MS4A10 transcripts were rare and not detected among hemat
opoietic cells and most nonlymphoid tissues. Sequence polymorphisms were id
entified in the MS4A6E gene and common splice variants were observed for th
e MS4A4A, MS4A5, MS4A6A, and MS4A7 genes. Thus, the MS4A family currently i
ncludes 24 distinct human and mouse genes. Like CD20 and Fc epsilon RI beta
, the 10 other human MS4A family members are likely to be components of oli
gomeric cell surface complexes involved in signal transduction in diverse c
ell lineages.