HGNC Approved Gene Symbol: RPS29
Cytogenetic location: 14q21.3 Genomic coordinates (GRCh38) : 14:49,570,988-49,598,710 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 14q21.3 | Diamond-Blackfan anemia 13 | 615909 | Autosomal dominant | 3 |
The RPS29 gene encodes a component of the small 40S ribosomal subunit and is essential for rRNA processing and ribosomal biogenesis (summary by Mirabello et al., 2014).
By searching sequence databases with the partial sequences of randomly selected cDNAs from a human colorectal cDNA library, Frigerio et al. (1995) identified cDNAs encoding homologs of rat ribosomal proteins S5 (RPS5; 603630), S9 (RPS9; 603631), S10 (RPS10; 603632), S29 (RPS29), L5 (RPL5; 603634), L21 (RPL21; 603636), L27a (RPL27A; 603637), and L28 (RPL28; 603638). Frigerio et al. (1995) completed the cDNA sequences of these human ribosomal proteins. The deduced 56-amino acid human RPS29 is identical to rat Rps29. Northern blot analysis suggested variable expression of RPS29 in colorectal cancers compared to adjacent normal tissues, although no correlation between the level of expression and the severity of the disease was found.
Kondoh et al. (1996) isolated RPS29 cDNAs by differential hybridization screening of a human colon carcinoma cDNA library with probes derived from a colon carcinoma cell line (HT29) and a differentiated subclone (C III). Northern blot analysis detected higher levels of the 0.3-kb RPS29 transcript in the undifferentiated HT29 cells compared to the differentiated C III cells, and in growth-arrested HT29 cells compared to rapidly proliferating HT29 cells. RPS29 has a zinc finger-like domain that can bind zinc. The authors demonstrated that RPS29 can enhance the tumor suppressor activity of KREV1 (179520).
By somatic cell hybrid and radiation hybrid mapping analyses, Kenmochi et al. (1998) mapped the human RPS29 gene to chromosome 14q.
In affected members of 2 unrelated families with Diamond-Blackfan anemia-13 (DBA13; 615909), Mirabello et al. (2014) identified heterozygous missense mutations in the RPS29 gene (603633.0001 and 603633.0002). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the families; however, both families showed evidence of incomplete penetrance. Functional studies showed that the mutations caused haploinsufficiency of RPS29.
In 5 affected members of a family with Diamond-Blackfan anemia-13 (DBA13; 615909), Mirabello et al. (2014) identified a heterozygous c.121T-A transversion in exon 2 of the RPS29 gene, resulting in an ile31-to-phe (I31F) substitution at a highly conserved residue in an important structural domain. The mutation, which was found by whole-exome sequencing and validated by direct sequencing, was not present in the Exome Sequencing Project, dbSNP (build 137), or 1000 Genomes Project databases, or in 1,000 in-house control exomes. One unaffected family member did not carry the mutation, but another unaffected family member did carry it, indicating incomplete penetrance. Patient cells showed haploinsufficiency for the canonical RPS29 isoform as well as defects in pre-rRNA processing, with incomplete maturation of the 3-prime end of the 18S rRNA subunit.
In a 25-year-old man with DBA13 (615909), Mirabello et al. (2014) identified a heterozygous c.179A-G transition in exon 2 of the RPS29 gene, resulting in an ile50-to-thr (I50T) substitution at a highly conserved residue in an important structural domain. The mutation, which was found by whole-exome sequencing and validated by direct sequencing, was not present in the Exome Sequencing Project, dbSNP (build 137), or 1000 Genomes Project databases, or in 1,000 in-house control exomes. One obligate carrier had increased erythrocyte adenosine deaminase, and another obligate carrier was unaffected, indicating incomplete penetrance. Patient cells showed haploinsufficiency for the canonical RPS29 isoform. Expression of the I50T mutation in rps29-null zebrafish failed to rescue the hematopoietic defect.
Frigerio, J.-M., Berthezene, P., Garrido, P., Ortiz, E., Barthellemy, S., Vasseur, S., Sastre, B., Seleznieff, I., Dagorn, J. C., Iovanna, J. L. Analysis of 2166 clones from a human colorectal cancer cDNA library by partial sequencing. Hum. Molec. Genet. 4: 37-43, 1995. [PubMed: 7711732] [Full Text: https://doi.org/10.1093/hmg/4.1.37]
Frigerio, J.-M., Dagorn, J.-C., Iovanna, J. L. Cloning, sequencing and expression of the L5, L21, L27a, L28, S5, S9, S10 and S29 human ribosomal protein mRNAs. Biochim. Biophys. Acta 1262: 64-68, 1995. [PubMed: 7772601] [Full Text: https://doi.org/10.1016/0167-4781(95)00045-i]
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]
Kondoh, N., Noda, M., Fisher, R. J., Schweinfest, C. W., Papas, T. S., Kondoh, A., Samuel, K. P., Oikawa, T. The S29 ribosomal protein increases tumor suppressor activity of Krev-1 gene on v-Kras-transformed NIH3T3 cells. Biochim. Biophys. Acta 1313: 41-46, 1996. [PubMed: 8781548] [Full Text: https://doi.org/10.1016/0167-4889(96)00052-3]
Mirabello, L., Macari, E. R., Jessop, L., Ellis, S. R., Myers, T., Giri, N., Taylor, A. M., McGrath, K. E., Humphries, J. M., Ballew, B. J., Yeager, M., Boland, J. F., He, J., Hicks, B. D., Burdett, L., Alter, B. P., Zon, L., Savage, S. A. Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families. Blood 124: 24-32, 2014. [PubMed: 24829207] [Full Text: https://doi.org/10.1182/blood-2013-11-540278]