RPS19

RPS19 is a gene that encodes ribosomal protein S19, a small, basic protein that becomes part of the 40S small ribosomal subunit in eukaryotic cells. The protein associates with 18S ribosomal RNA during ribosome biogenesis and contributes to the structure and function of the mature small subunit, influencing translation initiation and elongation as part of the intact ribosome.

The RPS19 gene is located on chromosome 19 and is widely expressed, with higher levels in rapidly dividing tissues such as the bone marrow. As a component of the ribosome, RPS19 participates in the fundamental process of protein synthesis and interacts with other ribosomal components during assembly in the nucleolus and cytoplasm.

Mutations in RPS19 cause Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia. RPS19 defects are among the more commonly identified ribosomal protein gene abnormalities in DBA and are typically inherited in an autosomal dominant pattern with variable expressivity, though de novo mutations occur. The disease is characterized by severe anemia due to impaired erythroid progenitor development, often accompanied by congenital anomalies. The pathogenesis is linked to haploinsufficiency of ribosome biogenesis and activation of the p53 pathway, which can suppress erythroid cell proliferation.

Diagnosis is established by genetic testing identifying pathogenic variants in RPS19. Management is supportive and may include corticosteroids, transfusions, iron chelation, and, in selected cases, hematopoietic stem cell transplantation. RPS19 is conserved across eukaryotes, with functional homologs in other species informing studies of ribosome assembly and related disorders.