*4.3. Class 1 Mutations*

The next group is composed of mutations that impair protein production (Class 1). Among them, Q126X (rs72552713) is the most frequent with a MAF of 0.002 in the Asian population [108]. This mutation leads to an early stop codon; thus, no protein is produced. Several other, mainly nonsense mutations, e.g., R113X, R236X, R246X, G262X, E334X, and Q531X, result in a protein with severe structural and folding problems, and consequently in rapid protein degradation. Some other types of mutations, such as the deletion S340del, the frameshift L264Hfs, as well as the missense R147W, F208S, and R383C mutations [104,107], also belong to this group. A link between the lack of ABCG2 expression and the rare blood group Jr(a–) was established in 2012 [109,110]. Interestingly, individuals carrying Class 1 mutations on both alleles have no ABCG2 present in their RBC membranes, but exhibit no apparent signs of diseases. However, they can have transfusion reactions, and can

be sensitive to drugs that are ABCG2 substrates, the concentration of which is normally controlled by the transporter.
