HGNC Approved Gene Symbol: RPL35
Cytogenetic location: 9q33.3 Genomic coordinates (GRCh38): 9:124,857,883-124,861,957 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 9q33.3 | ?Diamond-Blackfan anemia 19 | 618312 | Autosomal dominant | 3 |
RPL35 appears to function as an endoplasmic reticulum (ER) docking protein for the ribosome (Chen et al., 2008).
In their review, Wool et al. (1995) reported that the 123-amino acid human RPL35 protein shares 98% amino acid identity with its 122-amino acid rat ortholog, which is associated with the 60S ribosomal subunit.
Chen et al. (2008) cloned RPL35 from a human liver cDNA library. By phylogenetic analysis, they identified a 54-amino acid eukaryotic expansion segment at the C-terminal end of RPL35. Immunofluorescence analysis of transfected HeLa cells showed that full-length RPL35 localized to nucleolus.
By mutation analysis, Chen et al. (2008) determined that amino acids 69 to 94 of human RPL35, within the C-terminal eukaryotic expansion segment, were required for nuclear import. The last 29 amino acids of the RPL35 eukaryotic expansion segment were not involved in ribosomal structural and translational functions, but they were involved in ribosomal docking to the ER.
Gross (2019) mapped the RPL35 gene to chromosome 9q33.3 based on an alignment of the RPL35 sequence (GenBank BC000348) with the genomic sequence (GRCh38).
In a mother and daughter with Diamond-Blackfan anemia-19 (DBA19; 618312), Mirabello et al. (2017) identified a heterozygous missense mutation in the RPL35 gene (K77N; 618315.0001). Analysis of pre-rRNA processing in patient cells showed abnormal levels of several pre-rRNA subunits, indicating a defect in pre-rRNA processing.
In a mother and daughter with Diamond-Blackfan anemia-19 (DBA19; 618312), Mirabello et al. (2017) identified a heterozygous mutation (g.127620338G-C, GRCh37) in the RPL35 gene, resulting in a lys77-to-asn (K77N) substitution. The mutation, which was found by whole-exome sequencing, was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases. Analysis of pre-rRNA processing in patient cells showed abnormal levels of several pre-rRNA subunits, indicating a defect in pre-rRNA processing. The patients were part of a cohort of 87 families with a similar disorder who underwent genetic analysis; mutations in known DBA-associated genes were excluded in the family.
Chen, I.-J., Wang, I.-A., Tai, L.-R., Lin, A. The role of expansion segment of human ribosomal protein L35 in nuclear entry, translation activity, and endoplasmic reticulum docking. Biochem. Cell Biol. 86: 271-277, 2008. [PubMed: 18523488] [Full Text: https://doi.org/10.1139/o08-032]
Gross, M. B. Personal Communication. Baltimore, Md. 2/4/2019.
Mirabello, L., Khincha, P. P., Ellis, S. R., Giri, N., Brodie, S., Chandrasekharappa, S. C., Donovan, F. X., Zhou, W., Hicks, B. D., Boland, J. F., Yeager, M., Jones, K., Zhu, B., Wang, M., Alter, B. P., Savage, S. A. Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation. J. Med. Genet. 54: 417-425, 2017. [PubMed: 28280134] [Full Text: https://doi.org/10.1136/jmedgenet-2016-104346]
Wool, I. G., Chan, Y.-L., Gluck, A. Structure and evolution of mammalian ribosomal proteins. Biochem. Cell Biol. 73: 933-947, 1995. [PubMed: 8722009] [Full Text: https://doi.org/10.1139/o95-101]