HGNC Approved Gene Symbol: RPS28
Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38) : 19:8,321,496-8,323,340 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19p13.2 | Diamond Blackfan anemia 15 with mandibulofacial dysostosis | 606164 | Autosomal dominant | 3 |
The RPS28 gene encodes a ribosomal protein likely involved in ribosome biogenesis (summary by Gripp et al., 2014). The mammalian ribosome is composed of 4 RNA species (see 180450) and approximately 80 different proteins.
Chan et al. (1991) cloned and characterized a rat ribosomal protein S28 (Rps28) cDNA. They deposited the sequence of a human RPS28 cDNA in GenBank (L05091).
By somatic cell hybrid and radiation hybrid mapping analyses, Kenmochi et al. (1998) mapped the human RPS28 gene to 19p13.2 (GenBank AB007164).
Transfer RNA-derived small RNAs (tsRNAs; also called tRNA-derived fragments) are an abundant class of small noncoding RNAs. Kim et al. (2017) showed that inhibition of a specific tsRNA, LeuCAG-3-prime-tsRNA, induced apoptosis in rapidly dividing cells in vitro and in a patient-derived orthotopic hepatocellular carcinoma model in mice. This tsRNA binds at least 2 ribosomal protein mRNAs (RPS28 and RPS15, 180535) to enhance their translation. A decrease in translation of RPS28 mRNA blocks pre-18S ribosomal RNA processing, resulting in a reduction in the number of 40S ribosomal subunits. Kim et al. (2017) concluded that their data established a posttranscriptional mechanism that can fine tune gene expression during different physiologic states and provided a potential target for treating cancer.
In 2 unrelated girls with Diamond-Blackfan anemia-15 and mandibulofacial dysostosis (DBA15; 606164), Gripp et al. (2014) identified the same de novo heterozygous mutation affecting the translation initiation codon of the RPS28 gene (c.1A-G; 603685.0001), predicted to result in haploinsufficiency. Functional studies of the variant were not performed, but Gripp et al. (2014) noted that RPS28 interacts with other RPS proteins to generate ribosomes, and that the mutation may be comparable to the loss of RPS19 (603474), which is mutated in DBA1 (105650).
In 2 unrelated girls (patients 4 and 5) with Diamond-Blackfan anemia-15 and mandibulofacial dysostosis (DBA15; 606164), Gripp et al. (2014) identified the same de novo heterozygous c.1A-G transition affecting the translation initiation codon of the RPS28 gene (met1 to val), predicted to result in haploinsufficiency. The mutation was found by sequencing of candidate ribosomal protein genes. One of the patients had loss of the mutant allele and SNPs on 19p in peripheral blood cells, but not in buccal DNA, whereas the other patient had loss of the mutant allele and SNPs on 19p in buccal DNA only. It was not known whether this tissue-specific allelic imbalance contributed to the clinical presentation.
Chan, Y.-L., Olvera, J., Wool, I. G. The primary structure of rat ribosomal protein S28. Biochem. Biophys. Res. Commun. 179: 314-318, 1991. [PubMed: 1679328] [Full Text: https://doi.org/10.1016/0006-291x(91)91371-i]
Gripp, K. W., Curry, C., Olney, A. H., Sandoval, C., Fisher, J., Chong, J. X.-L., UW Center for Mendelian Genomics, Pilchman, L., Sahraoui, R., Stabley, D. L., Sol-Church, K. Diamond-Blackfan anemia with mandibulofacial dystostosis (sic) is heterogeneous, including the novel DBA genes TSR2 and RPS28. Am. J. Med. Genet. 164A: 2240-2249, 2014. [PubMed: 24942156] [Full Text: https://doi.org/10.1002/ajmg.a.36633]
Kenmochi, N., Kawaguchi, T., Rozen, S., Davis, E., Goodman, N., Hudson, T. J., Tanaka, T., Page, D. C. A map of 75 human ribosomal protein genes. Genome Res. 8: 509-523, 1998. [PubMed: 9582194] [Full Text: https://doi.org/10.1101/gr.8.5.509]
Kim, H. K., Fuchs, G., Wang, S., Wei, W., Zhang, Y., Park, H., Roy-Chaudhuri, B., Li, P., Xu, J., Chu, K., Zhang, F., Chua, M.-S., So, S., Zhang, Q. C., Sarnow, P., Kay, M. A. A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature 552: 57-62, 2017. [PubMed: 29186115] [Full Text: https://doi.org/10.1038/nature25005]