The system can be thought of as two separate groups: the M and N antigens are at one location on the ECM and S, s, and U are on a closely related location. The two groups are very close together on the chromosome and are typically inherited together.
M+ and N+ are common (75% of population) and M+N+ is the most common genotype (50% of population). These were an early discovery and are some of the oldest blood antigens known after the ABO system. They were first described by Landsteiner and Levine in 1927. Anti-M and anti-N antigens are rarely associated with transfusion reactions.
Anti-N is sometimes seen in dialysis patients due to cross-reactions with the residual formaldehyde from sterilizing the equipment. This is usually irrelevant for transfusion since this variant of the antibody does not react at body temperature.
The S antigen is relatively common (~55% of the population) and the s antigen is very common (~89% of the population). Anti-S and anti-s will usually cause transfusion reactions if an incompatible unit is transfused.
The U antigen is extremely common (>99.9% of the population), and the U was originally short for "Universal." It is not universal, and the U- phenotype is sometimes present in people of African descent with a mutation in red cell surface structure that also makes them S- and s-. This mutation and similar ones that result in lack of common MNS antigens appear to provide some resistance to malaria. Anti-U has been associated with both hemolytic transfusion reactions and hemolytic disease of the newborn.
The other 35 identified antigens in the MNS group are either extremely rare, such as He (0.8% of the population) or extremely common, such as ENa (>99.9% of the population).