HGNC Approved Gene Symbol: RPS7
Cytogenetic location: 2p25.3 Genomic coordinates (GRCh38) : 2:3,575,260-3,580,920 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p25.3 | Diamond-Blackfan anemia 8 | 612563 | Autosomal dominant | 3 |
The eukaryotic ribosome consists of more than 80 different ribosomal proteins, including RPS7, and 4 RNA species (see 180450).
Annilo et al. (1995) isolated cDNAs encoding RPS7 by screening a human cDNA expression library with antibodies against rat Rps7. The deduced 194-amino acid human RPS7 protein is identical to rat Rps7. Northern blot analysis detected an approximately 0.7-kb RPS7 transcript in HeLa cells. The authors identified several RPS7 pseudogenes.
Annilo et al. (1995) determined that the RPS7 gene contains 7 exons and spans over 6 kb.
By FISH, Annilo et al. (1995) mapped the RPS7 gene to chromosome 2p25. Kenmochi et al. (1998) confirmed the mapping assignment reported by Annilo et al. (1995).
By yeast 2-hybrid screening of a human testis cDNA library, Sato et al. (2011) identified RPS7 and RPL13A (619225) as SRY (480000)-interacting proteins. Pull-down assay confirmed that the HMG box of SRY was required for its interaction with RPS7 and RPL13A. In transiently transfected COS1 cells, SRY, RPS7, and RPL13A colocalized in nuclear speckles.
Gazda et al. (2008) screened 196 probands with Diamond-Blackfan anemia (see DBA8, 612563) for mutations in 25 genes encoding ribosomal proteins and identified a splice site mutation in the RPS7 gene in 1 proband (603658.0001). The mutation was not found in his unaffected sister or at least 150 controls, and functional studies strongly suggested that mutation in RPS7 is associated with defects in the maturation of ribosomal RNAs.
Gerrard et al. (2013) screened a cohort of 19 patients with DBA for mutations in 80 ribosomal protein genes and identified a heterozygous splice site mutation in the RPS7 gene (603658.0001) in 1 patient.
By whole-exome sequencing in a Japanese mother and daughter with DBA, Ichimura et al. (2017) identified heterozygosity for a splice site mutation in the RPS7 gene (603658.0002).
Watkins-Chow et al. (2013) described 2 N-ethyl-N-nitrosourea (ENU)-induced mouse mutants of Rps7: montu (Mtu), which results in a val156-to-gly (V156G) substitution at a highly conserved residue, and zuma (Zma), which results in a tyr177-to-ser (Y177S) substitution at a conserved residue. Mtu was dominant lethal with incomplete penetrance, whereas survival in Zma heterozygotes depended on the genetic background. Both mutations impaired ribosomal biogenesis and caused reduced body size accompanied by abnormal skeletal, melanocyte, eye, and central nervous system development, as well as deficits in working memory. Neither mutation caused anemia or hyperpigmentation. Loss of Rps7 increased expression of Trp53 (TP53; 191170), and crossing the Zma mutation onto a Trp53 +/- background largely suppressed the Zma phenotype.
In a male patient with Diamond-Blackfan anemia (DBA8; 612563) who had no associated malformations, Gazda et al. (2008) identified heterozygosity for a G-A transition at the donor splice site in intron 3 (IVS3+1G-A) of the RPS7 gene. The mutation was not found in his unaffected sister or in at least 150 controls. Lymphoblastoid cells established from the patient's cells displayed higher levels of 45S and 30S pre-rRNAs compared to cells derived from an unaffected sibling; siRNA knockdown of RPS7 synthesis in HeLa cells resulted in a strong defect in 5-prime ETS processing, with accumulation of 45S and 30S pre-rRNAs and a marked decrease in the 41S, 21S, and 18S-E intermediates, whereas levels of precursors to the large ribosomal subunit RNAs were unchanged.
Gerrard et al. (2013) identified a c.147+1G-T mutation in intron 3 of the RPS7 gene in 1 of 19 patients with DBA who were screened for mutations in 80 ribosomal protein genes. Gerrard et al. (2013) stated that this was the same splice site mutation previously reported as a G-to-A change by Gazda et al. (2008). The patient (S12) was a 10-year-old Caucasian girl who was diagnosed at age 2 months. She had growth retardation, Cathie facies, and neutropenia. She underwent bone marrow transplantation from an unaffected sib.
In a Japanese mother and daughter with Diamond-Blackfan anemia (DBA8; 612563), Ichimura et al. (2017) identified heterozygosity for a splicing error (exon 3, c.76-1G-T) in the RPS7 gene.
Annilo, T., Laan, M., Stahl, J., Metspalu, A. The human ribosomal protein S7-encoding gene: isolation, structure and localization in 2p25. Gene 165: 297-302, 1995. [PubMed: 8522193]
Gazda, H. T., Sheen, M. R., Vlachos, A., Choesmel, V., O'Donohue, M.-F., Schneider, H., Darras, N., Hasman, C., Sieff, C. A., Newburger, P. E., Ball, S. E., Niewiadomska, E., and 9 others. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am. J. Hum. Genet. 83: 769-780, 2008. [PubMed: 19061985] [Full Text: https://doi.org/10.1016/j.ajhg.2008.11.004]
Gerrard, G., Valganon, M., Foong, H. E., Kasperaviciute, D., Iskander, D., Game, L., Muller, M., Aitman, T. J., Roberts, I., de la Fuente, J., Foroni, L., Karadimitris, A. Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. Brit. J. Haemat. 162: 530-536, 2013. [PubMed: 23718193] [Full Text: https://doi.org/10.1111/bjh.12397]
Ichimura, T., Yoshida, K., Okuno, Y., Yujiri, T., Nagai, K., Nishi, M., Shiraishi, Y., Ueno, H., Toki, T., Chiba, K., Tanaka, H., Muramatsu, H., Hara, T., Kanno, H., Kojima, S., Miyano, S., Ito, E., Ogawa, S., Ohga, S. Diagnostic challenge of Diamond-Blackfan anemia in mothers and children by whole-exome sequencing. Int. J. Hemat. 105: 515-520, 2017. [PubMed: 27882484] [Full Text: https://doi.org/10.1007/s12185-016-2151-7]
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]
Sato, Y., Yano, S., Ewis, A. A., Nakahori, Y. SRY interacts with ribosomal proteins S7 and L13a in nuclear speckles. Cell Biol. Int. 35: 449-452, 2011. [PubMed: 21114473] [Full Text: https://doi.org/10.1042/CBI20090201]
Watkins-Chow, D. E., Cooke, J., Pidsley, R., Edwards, A., Slotkin, R., Leeds, K. E., Mullen, R., Baxter, L. L., Campbell, T. G., Salzer, M. C., Biondini, L., Gibney, G., and 10 others. Mutation of the Diamond-Blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes. PLoS Genet. 9: e1003094, 2013. Note: Electronic Article. Erratum: PLoS Genet. 11: e1005682, 2015. [PubMed: 23382688] [Full Text: https://doi.org/10.1371/journal.pgen.1003094]