The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

RPS19  -  ribosomal protein S19

Homo sapiens

Synonyms: 40S ribosomal protein S19, DBA, DBA1, S19
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of RPS19


High impact information on RPS19

  • Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions [6].
  • These mutations are associated with clinical features that suggest a function for RPS19 in erythropoiesis and embryogenesis [6].
  • We report identification of de novo nonsense and splice-site mutations in another RP, RPS24 (encoded by RPS24 [10q22-q23]) in approximately 2% of RPS19 mutation-negative probands [7].
  • Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands [7].
  • Studies where RPS19 expression is reduced by siRNA in the hematopoietic cell line, TF-1, show that human RPS19 is also required for a specific step in the maturation of 40S ribosomal subunits [1].

Chemical compound and disease context of RPS19


Biological context of RPS19

  • The lack of a consistent relationship between the nature of the mutations and the clinical phenotype implies that yet unidentified factors modulate the phenotypic expression of the primary genetic defect in families with RPS19 mutations [9].
  • To determine the prevalence of mutations in this gene in DBA and to begin to define the molecular basis for the observed variable clinical phenotype of this disorder, the genomic sequence of the 6 exons and the 5' untranslated region of the RPS19 gene was directly assessed in DBA index cases from 172 new families [9].
  • Transduction with the siRNA vectors reduced RPS19 mRNA levels to various degrees, which resulted in erythroid defects, correlating to the degree of RPS19 down-regulation, and was rescued by expression of an siRNA-resistant RPS19 transcript [10].
  • A hot spot for missense mutations was identified between codons 52 and 62 of the RPS19 gene in a new sequence consensus motif W-[YFW]-[YF]-x-R-[AT]-A-[SA]-x-[AL]-R-[HRK]-[ILV]-Y [9].
  • RESULTS AND STATE OF THE ART: We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation [11].

Anatomical context of RPS19

  • Analysis of these intermediates in CD34(-) cells from the bone marrow of patients with DBA harboring mutations in RPS19 revealed a pre-rRNA-processing defect similar to that observed in TF-1 cells where RPS19 expression was reduced [1].
  • In the present study, using wild-type and mutant RPS19 cDNA, we explored the subcellular distribution of normal and mutant proteins in a fibroblast cell line (Cos-7 cells) [12].
  • We demonstrate that targeted degradation of the RPS19 transcript, through retroviral expression of short hairpin RNAs (shRNAs), blocks the proliferation and differentiation of erythroid progenitor cells in cultured human CD34(+) cells [8].
  • Moreover, RPS19 mutations were also found in some first-degree relatives presenting only with isolated high erythrocyte adenosine deaminase activity and/or macrocytosis [9].
  • To study effects of RPS19 deficiency in hematopoiesis we transduced CD34(+) umbilical cord blood (CB) and bone marrow (BM) cells with 3 lentiviral vectors expressing small interfering RNA (siRNA) against RPS19 and 1 scrambled control vector [10].

Associations of RPS19 with chemical compounds

  • Treatment of RPS19-deficient cells with dexamethasone restores erythroid differentiation to normal levels [8].
  • Using various N-terminal and C-terminal deletion constructs, we identified 2 nucleolar localization signals (NoSs) in RPS19: the first comprising amino acids Met1 to Arg16 in the NH2-terminus and the second comprising Gly120 to Asn142 in the COOH-terminus [12].
  • Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis [2].

Physical interactions of RPS19

  • We showed that FGF-2 interacts directly with RPS19 in vitro [13].
  • RESULTS: We found that RPS19 binds PIM-1, an ubiquitous serine-threonine kinase whose expression can be induced in erythropoietic cells by several growth factors, such as erythropoietin [14].

Co-localisations of RPS19

  • RPS19 was detected primarily in the nucleus, and more specifically in the nucleoli, where RPS19 colocalized with the nucleolar protein nucleolin [12].

Regulatory relationships of RPS19


Other interactions of RPS19


Analytical, diagnostic and therapeutic context of RPS19

  • MATERIALS AND METHODS: We searched mutations in 48 DBA families or isolated patients based on PCR of exons of the rps19 gene and automatic sequencing [16].
  • We constructed oncoretroviral vectors containing the RPS19 gene to develop gene therapy for RPS19-deficient DBA [17].
  • To characterize further RPS19 mutations and to investigate genotype-phenotype relationships, we screened this gene for mutations in patients with DBA by direct sequencing and Southern-blot analysis [18].
  • In order to clarify whether TEC and DBA are allelic, we investigated the segregation of markers spanning the RPS19 gene region on chromosome 19q13.2 and performed sequence analysis of all exons in the RPS19 gene in seven TEC sibling pairs [19].
  • Using an immunofluorescence technique, the mutated RPS19 protein localized to nucleoli, and its intracellular distribution did not differ from the wild-type RPS19 [4].


  1. Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits. Flygare, J., Aspesi, A., Bailey, J.C., Miyake, K., Caffrey, J.M., Karlsson, S., Ellis, S.R. Blood (2007) [Pubmed]
  2. Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis. Léger-Silvestre, I., Caffrey, J.M., Dawaliby, R., Alvarez-Arias, D.A., Gas, N., Bertolone, S.J., Gleizes, P.E., Ellis, S.R. J. Biol. Chem. (2005) [Pubmed]
  3. S19-mRNA expression in squamous cell carcinomas of the upper aerodigestive tract. Sengpiel, V., Rost, T., Görögh, T., Rathcke, I.O., Werner, J.A. Anticancer Res. (2004) [Pubmed]
  4. Identification of a new in-frame deletion of six amino acids in ribosomal protein S19 in a patient with Diamond-Blackfan anemia. Cmejlova, J., Cerna, Z., Votava, T., Pospisilova, D., Cmejla, R. Blood Cells Mol. Dis. (2006) [Pubmed]
  5. Ribosomal protein S19 expression during erythroid differentiation. Da Costa, L., Narla, G., Willig, T.N., Peters, L.L., Parra, M., Fixler, J., Tchernia, G., Mohandas, N. Blood (2003) [Pubmed]
  6. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Draptchinskaia, N., Gustavsson, P., Andersson, B., Pettersson, M., Willig, T.N., Dianzani, I., Ball, S., Tchernia, G., Klar, J., Matsson, H., Tentler, D., Mohandas, N., Carlsson, B., Dahl, N. Nat. Genet. (1999) [Pubmed]
  7. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Gazda, H.T., Grabowska, A., Merida-Long, L.B., Latawiec, E., Schneider, H.E., Lipton, J.M., Vlachos, A., Atsidaftos, E., Ball, S.E., Orfali, K.A., Niewiadomska, E., Da Costa, L., Tchernia, G., Niemeyer, C., Meerpohl, J.J., Stahl, J., Schratt, G., Glader, B., Backer, K., Wong, C., Nathan, D.G., Beggs, A.H., Sieff, C.A. Am. J. Hum. Genet. (2006) [Pubmed]
  8. An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray. Ebert, B.L., Lee, M.M., Pretz, J.L., Subramanian, A., Mak, R., Golub, T.R., Sieff, C.A. Blood (2005) [Pubmed]
  9. Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression. Willig, T.N., Draptchinskaia, N., Dianzani, I., Ball, S., Niemeyer, C., Ramenghi, U., Orfali, K., Gustavsson, P., Garelli, E., Brusco, A., Tiemann, C., Pérignon, J.L., Bouchier, C., Cicchiello, L., Dahl, N., Mohandas, N., Tchernia, G. Blood (1999) [Pubmed]
  10. Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia. Flygare, J., Kiefer, T., Miyake, K., Utsugisawa, T., Hamaguchi, I., Da Costa, L., Richter, J., Davey, E.J., Matsson, H., Dahl, N., Wiznerowicz, M., Trono, D., Karlsson, S. Blood (2005) [Pubmed]
  11. Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature. Campagnoli, M.F., Garelli, E., Quarello, P., Carando, A., Varotto, S., Nobili, B., Longoni, D., Pecile, V., Zecca, M., Dufour, C., Ramenghi, U., Dianzan, I. Haematologica (2004) [Pubmed]
  12. Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology. Da Costa, L., Tchernia, G., Gascard, P., Lo, A., Meerpohl, J., Niemeyer, C., Chasis, J.A., Fixler, J., Mohandas, N. Blood (2003) [Pubmed]
  13. Fibroblast growth factor-2 interacts with free ribosomal protein S19. Soulet, F., Al Saati, T., Roga, S., Amalric, F., Bouche, G. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  14. Interactions between RPS19, mutated in Diamond-Blackfan anemia, and the PIM-1 oncoprotein. Chiocchetti, A., Gibello, L., Carando, A., Aspesi, A., Secco, P., Garelli, E., Loreni, F., Angelini, M., Biava, A., Dahl, N., Dianzani, U., Ramenghi, U., Santoro, C., Dianzani, I. Haematologica (2005) [Pubmed]
  15. Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes. Yamamoto, T. Pathol. Int. (2007) [Pubmed]
  16. Ten novel Diamond-Blackfan anemia mutations and three polymorphisms within the rps19 gene. Proust, A., Da Costa, L., Rince, P., Landois, A., Tamary, H., Zaizov, R., Tchernia, G., Delaunay, J. Hematol. J. (2003) [Pubmed]
  17. Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia. Hamaguchi, I., Ooka, A., Brun, A., Richter, J., Dahl, N., Karlsson, S. Blood (2002) [Pubmed]
  18. Truncating ribosomal protein S19 mutations and variable clinical expression in Diamond-Blackfan anemia. Matsson, H., Klar, J., Draptchinskaia, N., Gustavsson, P., Carlsson, B., Bowers, D., de Bont, E., Dahl, N. Hum. Genet. (1999) [Pubmed]
  19. Familial transient erythroblastopenia of childhood is associated with the chromosome 19q13.2 region but not caused by mutations in coding sequences of the ribosomal protein S19 (RPS19) gene. Gustavsson, P., Klar, J., Matsson, H., Forestier, E., Henter, J.I., Rao, S., Seip, M., Skeppner, G., Dahl, N. Br. J. Haematol. (2002) [Pubmed]
WikiGenes - Universities