The JR blood group system: from discovery to the clinic

In 2012, the International Society of Blood Transfusion (ISBT) formalized the JR blood group system (ISBT 032), with Jr^a (ISBT 032001) as its only antigen. Jr^a is located on a multipass membrane glycoprotein named ABCG2. ABCG2, or ATP-binding cassette subfamily G member 2, is also known as breast cancer resistance protein (BCRP) or CD338. This glycoprotein participates in various physiological, biochemical and metabolic processes in the human body. It is encoded by the ABCG2 gene, located on chromosome 4. In recent years, the ABCG2 gene variants have been gradually unraveled through the deeper study of the JR blood group system. Meanwhile, the JR blood group system is clinically important, being associated with fetal and neonatal anemia, hydrops fetalis, neonatal jaundice, hemolytic disease of the fetus and newborn (HDFN), and hemolytic transfusion reaction (HTR). Furthermore, its carrier molecule, ABCG2, is associated with hyperuricemia/gout and mirror syndrome. In addition, ABCG2 plays an important regulatory role in a variety of physiological and pathological processes, such as the regulation of uric acid metabolism, the maintenance of folate and porphyrin homeostasis, the regulation of blood-brain barrier substance exchange, and the regulation of anti-tumor drug transport and drug resistance. This study reviews the distributional characteristics, molecular biological features, immunological features and clinical significance of the JR blood group system and ABCG2.