Alternative titles; symbols
HGNC Approved Gene Symbol: RPL13
Cytogenetic location: 16q24.3 Genomic coordinates (GRCh38): 16:89,560,657-89,566,829 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 16q24.3 | Spondyloepimetaphyseal dysplasia, Isidor-Toutain type | 618728 | Autosomal dominant | 3 |
Adams et al. (1992) identified a novel cDNA representing an mRNA showing significantly higher levels of expression in benign breast lesions than in carcinomas. In both tissues, expression was highest in epithelial cells, as determined by in situ hybridization to tissue sections. The protein deduced from the nucleotide sequence was highly basic with no signal or transmembrane sequence, but 2 potential nuclear localization signals. The cDNA hybridized to multiple sequences within both human and other mammalian genomes and to single genomic sequences in Drosophila, Physarum, and Schizosaccharomyces pombe. Thus the cDNA represents a highly conserved gene sequence. Only 1 major transcript was identified in human cells, but the existence of several pseudogenes was suspected.
By immunohistochemistry in cross-sections of growth plate from 8-week-old healthy mice, Le Caignec et al. (2019) demonstrated expression of RPL13 in cells from the hypertrophic and remodeling zones. Weaker immunostaining was observed in cells located in the bone marrow compartment. Three other ribosomal proteins, RPL3 (604163), RPS3 (600454), and RPS10 (603632), were also detected in cells from the growth plate, and all 3 displayed the same localization pattern as RPL13.
By somatic cell hybrid and radiation hybrid analyses, Kenmochi et al. (1998) mapped the RPL13 gene to chromosome 16.
Le Caignec et al. (2019) stated that the RPL13 gene maps to 16q24.3.
Using siRNAs, Le Caignec et al. (2019) knocked down RPL13 in HeLa cells and observed severe alterations in the pre-rRNA pattern on Northern blot analysis. The most conspicuous effect was a defect in pre-rRNA cleavage, with accumulation of 41S pre-rRNA relative to 30S and 21S pre-rRNAs, and high levels of 36S and 36S-C pre-rRNAs. The authors also observed a drop in levels of 12S pre-rRNA relative to its precursor, 32S pre-rRNA. A similar pattern was observed in a control lymphoblastoid cell line treated with the same siRNAs.
Using knockdown analysis in hamster BHK-21 cells, Han et al. (2020) identified Rpl13 as an essential factor for replication of foot-and-mouth disease virus (FMDV). Rpl13 and Ddx3 (300160) interacted through the N-terminal region of Ddx3, and both proteins associated with the internal ribosome entry site (IRES) of the FMDV 5-prime UTR, thereby facilitating IRES-driven translation and promoting FMDV replication. The C-terminal region of Ddx3 was required for its association with the viral IRES. Rpl13 functioned downstream of Ddx3, and its interaction with the IRES was Ddx3 dependent. Ddx3 cooperated with Rpl13 to support assembly of 80S ribosomes for optimal translation initiation of FMDV mRNA, which also involved binding of Eif3e (602210) and Eif3j (603910) to the IRES. Further analysis demonstrated that the Rpl13 regulator function was also involved in infection of Seneca Valley virus and classical swine fever virus, but not vesicular stomatitis virus.
In 4 unrelated patients with the Isidor-Toutain type of spondyloepimetaphyseal dysplasia (SEMDIT; 618728), Le Caignec et al. (2019) identified de novo heterozygous mutations in the RPL13 gene (113703.0001-113703.0004) that were not found in public variant databases. Although the mutant proteins were stably expressed and incorporated into 60S ribosomal subunits similar to the wildtype protein, erythroid proliferation in culture and the ribosome profile on sucrose gradient were modified, suggesting a change in translation dynamics.
In a boy (P1) with the Isidor-Toutain type of spondyloepimetaphyseal dysplasia (SEMDIST; 618728), who was originally described by Isidor et al. (2013), Le Caignec et al. (2019) identified heterozygosity for a de novo splicing mutation (c.477+1G-T, NM_000977.3) in intron 5 of the RPL13 gene, leading to an 18-amino acid insertion (Asn159_Val160ins18). The mutation was not found in the dbSNP (build 138), 1000 Genomes Project, NHLBI GO Exome Sequencing Project, or ExAC/gnomAD databases. RT-PCR on RNA from patient peripheral blood showed an aberrant longer fragment, and Sanger sequencing revealed the inclusion of the first 54 bp of intron 5; Western blot analysis on protein lysates from mesenchymal stem cells confirmed the RT-PCR results. Analysis of total RNA from patient fibroblasts showed a normal pre-rRNA pattern, indicating that the mutant is incorporated into ribosomes to the same extent as wildtype RPL13.
In a boy (P2) with the Isidor-Toutain type of spondyloepimetaphyseal dysplasia (SEMDIST; 618728), who was originally described by Isidor et al. (2013), Le Caignec et al. (2019) identified heterozygosity for a de novo splicing mutation (c.477+2T-C, NM_000977.3) in intron 5 of the RPL13 gene, leading to an 18-amino acid insertion (Asn159_Val160ins18). The mutation was not found in the dbSNP (build 138), 1000 Genomes Project, NHLBI GO Exome Sequencing Project, or ExAC/gnomAD databases. RT-PCR on RNA from patient peripheral blood showed an aberrant longer fragment, and Sanger sequencing revealed the inclusion of the first 54 bp of intron 5; Western blot analysis on protein lysates from lymphoblastoid cells confirmed the RT-PCR results. Analysis of total RNA from patient lymphoblastoid cell lines showed a normal pre-rRNA pattern, indicating that the mutant is incorporated into ribosomes to the same extent as wildtype RPL13. Ribosome profile on a sucrose gradient in patient lymphoblastoid cells showed a normal ratio of free 40S to 60s subunits compared to control; however, the authors noted a decrease of 80S and polysome peaks in the patient sample, suggesting a change in translation dynamics. In addition, the authors studied erythrocyte proliferation using patient CD34+ cells and observed that only the late phase of terminal erythroid differentiation was affected in the patient sample.
In a male patient (P3) with the Isidor-Toutain type of spondyloepimetaphyseal dysplasia (SEMDIST; 618728), Le Caignec et al. (2019) identified heterozygosity for a de novo splicing mutation (c.477+1G-A, NM_000977.3) in intron 5 of the RPL13 gene, leading to an 18-amino acid insertion (Asn159_Val160ins18). The mutation was not found in the ExAC/gnomAD databases.
In a female patient (P4) with the Isidor-Toutain type of spondyloepimetaphyseal dysplasia (SEMDIST; 618728), Le Caignec et al. (2019) identified heterozygosity for a de novo c.548G-C transversion (c.548G-C, NM_000977.3) in exon 6 of the RPL13 gene, resulting in an arg183-to-pro (R183P) substitution at a highly conserved residue. The mutation was not found in the dbSNP (build 138), 1000 Genomes Project, NHLBI GO Exome Sequencing Project, or ExAC/gnomAD databases.
Adams, S. M., Helps, N. R., Sharp, M. G. F., Brammar, W. J., Walker, R. A., Varley, J. M. Isolation and characterization of a novel gene with differential expression in benign and malignant human breast tumours. Hum. Molec. Genet. 1: 91-96, 1992. [PubMed: 1301162] [Full Text: https://doi.org/10.1093/hmg/1.2.91]
Han, S., Sun, S., Li, P., Liu, Q., Zhang, Z., Dong, H., Sun, M., Wu, W., Wang, X., Guo, H. Ribosomal protein L13 promotes IRES-driven translation of foot-and-mouth disease virus in a helicase DDX3-dependent manner. J. Virol. 94: e01679-19, 2020. Note: Electronic Article. [PubMed: 31619563] [Full Text: https://doi.org/10.1128/JVI.01679-19]
Isidor, B., Geffroy, L., de Courtivron, B., Le Caignec, C., Thiel, C. T., Mortier, G., Cormier-Daire, V., David, A., Toutain, A. A new form of severe spondyloepimetaphyseal dysplasia: clinical and radiological characterization. Am. J. Med. Genet. 161A: 2645-2651, 2013. [PubMed: 23956136] [Full Text: https://doi.org/10.1002/ajmg.a.36132]
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]
Le Caignec, C., Ory, B., Lamoureux, F., O'Donohue, M.-F., Orgebin, E., Lindenbaum, P., Teletchea, S., Saby, M., Hurst, A., Nelson, K., Gilbert, S. R., Wilnai, Y., and 22 others. RPL13 variants cause spondyloepimetaphyseal dysplasia with severe short stature. Am. J. Hum. Genet. 105: 1040-1047, 2019. [PubMed: 31630789] [Full Text: https://doi.org/10.1016/j.ajhg.2019.09.024]