HGNC Approved Gene Symbol: RPL35A
Cytogenetic location: 3q29 Genomic coordinates (GRCh38): 3:197,950,190-197,956,610 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3q29 | Diamond-Blackfan anemia 5 | 612528 | Autosomal dominant | 3 |
In eukaryotes, the ribosome is composed of 4 different ribosomal RNA species and 79 ribosomal proteins, including RPL35A (Boria et al., 2010).
Boria et al. (2010) stated that the RPL35A gene encodes a 110-amino acid protein with a molecular mass of 12.4 kD.
Boria et al. (2010) stated that the RPL35A gene contains 6 exons spanning 5.6 kb. The first exon is noncoding.
By fluorescence in situ hybridization, Colombo et al. (1996) mapped the RPL35A to chromosome 3q29-qter. They confirmed the localization by PCR analysis of a hybrid cell line containing only chromosome 3.
Farrar et al. (2008) tested small hairpin RNAs (shRNA) targeting RPL35A mRNA in UT-7/Epo and TF-1 cell lines and demonstrated that RPL35A is essential for maturation of 28S and 5.8S rRNAs, 60S subunit biogenesis, normal proliferation, and cell survival.
Using a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray, Farrar et al. (2008) analyzed the chromosome 3q29-qter and 3q29 deletions, respectively, from a boy and an unrelated girl with Diamond-Blackfan anemia (DBA5; 612528), and identified RPL35A as a potential DBA gene. Screening genomic DNA from 148 additional probands with DBA, the authors identified 3 heterozygous mutations (180468.0001-180468.0003), yielding an estimated 3.3% rate of RPL35A abnormalities in DBA probands. Analysis of pre-rRNA processing in primary DBA lymphoblastoid cell lines demonstrated alterations of large ribosomal subunit rRNA in both RPL35A-mutated and RPL35A-wildtype DBA patients, suggesting that additional large ribosomal subunit gene defects are likely present in some cases of DBA.
Using a PCR product for the analysis of rodent/human somatic cell hybrids, Feo et al. (1992) incorrectly mapped the RPL35A gene to chromosome 18.
In a male patient (019) who presented with Diamond-Blackfan anemia (DBA5; 612528) at 4 months of age and who also had hypospadias and short stature, Farrar et al. (2008) identified heterozygosity for a 97G-A transition in exon 3 of the RPL35A gene, resulting in a val33-to-ile substitution (V33I) and selection of a cryptic splice donor site within exon 3 that causes a nonsense mutation after codon 31 and a 70-bp truncation of 3-prime exon 3 in addition to the intron. The mutation was also found in the proband's father and sister, who had untreated macrocytic anemia suggestive of subclinical DBA, but was not found in unaffected family members or 180 controls.
In a male patient (D9) who presented with Diamond-Blackfan anemia (DBA5; 612528) at 14 months of age and had no associated anomalies, Farrar et al. (2008) identified a heterozygous 3-bp deletion in exon 3 of the RPL35A gene (82_84delCTT), resulting in the deletion of leucine at codon 27 (leu27del). The mutation was not found in 2 unaffected sibs or in 180 controls.
In a male patient (E2) who presented with Diamond-Blackfan anemia (DBA5; 612528) at 2 months of age and who also had bilateral duplicated ureters and 11 ribs, Farrar et al. (2008) identified a 304C-T transition in exon 4 of the RPL35A gene, resulting in an arg102-to-ter (R102X) substitution and truncation of 9 C-terminal amino acids. The mutation was not found in 180 controls.
Boria, I., Garelli, E., Gazda, H. T., Aspesi, A., Quarello, P., Pavesi, E., Ferrante, D., Meerpohl, J. J., Kartal, M., Da Costa, L., Proust, A., Leblanc, T., and 17 others. The ribosomal basis of Diamond-Blackfan anemia: mutation and database update. Hum. Mutat. 31: 1269-1279, 2010. [PubMed: 20960466] [Full Text: https://doi.org/10.1002/humu.21383]
Colombo, P., Read, M., Fried, M. The human L35a ribosomal protein (RPL35A) gene is located at chromosome band 3q29-qter. Genomics 32: 148-150, 1996. [PubMed: 8786106] [Full Text: https://doi.org/10.1006/geno.1996.0093]
Farrar, J. E., Nater, M., Caywood, E., McDevitt, M. A., Kowalski, J., Takemoto, C. M., Talbot, C. C., Jr., Meltzer, P., Esposito, D., Beggs, A. H., Schneider, H. E., Grabowska, A., and 9 others. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood 112: 1582-1592, 2008. [PubMed: 18535205] [Full Text: https://doi.org/10.1182/blood-2008-02-140012]
Feo, S., Davies, B., Fried, M. The mapping of seven intron-containing ribosomal protein genes shows they are unlinked in the human genome. Genomics 13: 201-207, 1992. [PubMed: 1577483] [Full Text: https://doi.org/10.1016/0888-7543(92)90221-d]