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HGNC Approved Gene Symbol: RPS20
Cytogenetic location: 8q12.1 Genomic coordinates (GRCh38) : 8:56,067,254-56,074,506 (from NCBI)
The RPS20 gene encodes a protein required during the late steps of 18S ribosomal RNA (rRNA) formation (summary by Nieminen et al., 2014).
The mammalian ribosome is composed of 4 RNA species (see 180450) and approximately 80 different proteins.
Chu et al. (1993) isolated a human dermal vascular endothelial cell cDNA encoding ribosomal protein S20 (RPS20). The deduced 119-amino acid human RPS20 protein is identical to rat Rps20. Northern blot analysis detected an approximately 650-bp RPS20 transcript. Southern blot analysis showed that the RPS20 gene may be a member of a multigene family.
By somatic cell hybrid and radiation hybrid mapping analyses, Kenmochi et al. (1998) mapped the human RPS20 gene to chromosome 8q.
Nieminen et al. (2014) stated that the RPS20 gene maps to 8q12.1.
For discussion of a possible association between hereditary nonpolyposis colorectal cancer (see, e.g., HNPCC1, 120435) and variation in the RPS20 gene, see 603682.0001.
McGowan et al. (2008) reported 2 mouse 'dark skin' loci, Dsk3 and Dsk4, caused by mutations in Rps19 (603474) and Rps20, respectively. These mice have dark paws, tail skin, and ears, with melanocytosis limited to the epidermis. In the model proposed by McGowan et al. (2008), reduced dosage of Rps6 (180460), Rps19, or Rps20 triggers stabilization and/or activation of p53 (191170), which gives rise to a pleiotropic phenotype whose components depend on the sensitivity and response of individual cell types and on specific downstream targets of p53. Stabilization of p53 stimulates Kit ligand (KITLG; 184745) expression and, consequently, epidermal melanocytosis via a paracrine mechanism. Increased apoptosis causes erythrocyte hypoplasia and anemia, and activation of p53 causes reduced growth and decreased body size. McGowan et al. (2008) concluded that their results provide a mechanistic explanation for the diverse collection of phenotypes that accompany reduced dosage of genes encoding ribosomal proteins, and have implications for understanding normal human variation and human disease.
This variant is classified as a variant of unknown significance because its contribution to hereditary nonpolyposis colorectal cancer (see, e.g., HNPCC1, 120435) has not been confirmed.
In 7 affected members of a Finnish family (FCCX family F56) with hereditary nonpolyposis colorectal cancer with onset between 24 and 75 years of age, Nieminen et al. (2014) identified a heterozygous 1-bp duplication (c.147dupA, NM_001023.3) in the RPS20 gene, resulting in a frameshift and premature termination (Val50SerfsTer23). The mutation, which was found by exome sequencing, segregated with the disorder in the family and was not found in the Exome Variant Server database or in 584 control alleles. Tumors from mutation carriers did not show loss of the wildtype allele, arguing against RPS20 acting as a tumor suppressor gene. Patient lymphoblastoid cells showed a marked increase in 21S pre-rRNAs compared to controls, consistent with a late pre-rRNA processing defect and suggestive of RPS20 haploinsufficiency. Nieminen et al. (2014) suggested that the RPS20 mutation likely disturbed ribosome biogenesis by affecting the equilibrium between different pre-rRNA species and the formation of mature 18S rRNA. RPS20 mutations were not found in DNA from 25 additional Finnish families with colorectal cancer or in tumor cells from 61 primary colorectal cancers and cancer cell lines.
Chu, W., Presky, D. H., Swerlick, R. A., Burns, D. K. Human ribosomal protein S20 cDNA sequence. Nucleic Acids Res. 21: 1672 only, 1993. [PubMed: 8479924] [Full Text: https://doi.org/10.1093/nar/21.7.1672]
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]
McGowan, K. A., Li, J. Z., Park, C. Y., Beaudry, V., Tabor, H. K., Sabnis, A. J., Zhang, W., Fuchs, H., de Angelis, M. H., Myers, R. M., Attardi, L. D., Barsh, G. S. Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects. Nature Genet. 40: 963-970, 2008. [PubMed: 18641651] [Full Text: https://doi.org/10.1038/ng.188]
Nieminen, T. T., O'Donohue, M.-F., Wu, Y., Lohi, H., Scherer, S. W., Paterson, A. D., Ellonen, P., Abdel-Rahman, W. M., Valo, S., Mecklin, J.-P., Jarvinen, H. J., Gleizes, P.-E., Peltomaki, P. Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency. Gastroenterology 147: 595-598, 2014. [PubMed: 24941021] [Full Text: https://doi.org/10.1053/j.gastro.2014.06.009]