HGNC Approved Gene Symbol: MRPS7
SNOMEDCT: 1260133007;
Cytogenetic location: 17q25.1 Genomic coordinates (GRCh38): 17:75,261,879-75,266,376 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q25.1 | ?Combined oxidative phosphorylation deficiency 34 | 617872 | Autosomal recessive | 3 |
The MRPS7 gene encodes a 12S ribosomal RNA-binding subunit of the small mitochondrial ribosomal subunit (summary by Menezes et al., 2015).
Mitochondria have their own translation system for production of 13 proteins essential for oxidative phosphorylation. MRPS7 is 1 of more than 70 protein components of mitochondrial ribosomes that are encoded by the nuclear genome (Kenmochi et al., 2001).
By proteolytic digestion of whole bovine 28S subunits, followed by peptide analysis and EST database analysis, Koc et al. (2001) identified full-length human MRPS7. The deduced 242-amino acid MRPS7 protein has a calculated molecular mass of 28.2 kD. Removal of a predicted 37-amino acid N-terminal mitochondrial localization signal results in a mature 24.1-kD protein. Koc et al. (2001) identified MRPS7 orthologs in mouse, Drosophila, C. elegans, yeast, and E. coli. Mouse and human MRPS7 share 84.6% amino acid identity.
By radiation hybrid analysis and analysis of an integrated BAC-STS map, Kenmochi et al. (2001) mapped the MRPS7 gene to chromosome 17q23-q25.
In 2 sisters, born of unrelated Australian parents, with combined oxidative phosphorylation deficiency-34 (COXPD34; 617872), Menezes et al. (2015) identified a homozygous missense mutation in the MRPS7 gene (M184V; 611974.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The patients had variable deficiencies of mitochondrial complexes I, III, and IV in various tissues. Patient fibroblasts showed decreased levels of MRPS7 mRNA and protein, as well as decreased ATP production (80% of controls), decreased complex I activity (7.3% of controls), decreased complex IV activity (58.5% of controls), decreased mitochondrial protein synthesis (54% of controls), decreased 12S rRNA, and fragmentation of the mitochondrial network. These defects could be rescued by expression of wildtype MRPS7. The findings indicated that MRPS7 is an important component of the mitochondrial ribosome and plays a role in mitochondrial translation and functioning of the OXPHOS system.
In 2 sisters, born of unrelated Australian parents, with combined oxidative phosphorylation deficiency-34 (COXPD34; 617872), Menezes et al. (2015) identified a homozygous c.550A-G transition in the MRPS7 gene, resulting in a met184-to-val (M184V) substitution at a highly conserved residue in the hydrophobic core of the protein. The older sister (patient 1) had previously been reported by Freckmann et al. (1997). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was found at a low frequency in the dbSNP database (0.002) and in an in-house database (0.67%). Molecular modeling predicted that the mutation would destabilize the protein. Fibroblasts derived from 1 of the patients showed decreased levels of MRPS7 mRNA and protein, as well as decreased ATP production (80% of controls), decreased complex I activity (7.3% of controls), decreased complex IV activity (58.5% of controls), decreased mitochondrial protein synthesis (54% of controls), decreased 12S rRNA, and fragmentation of the mitochondrial network. These defects could be rescued by expression of wildtype MRPS7.
Freckmann, M.-L., Thorburn, D. R., Kirby, D. M., Kamath, K. R., Hammond, J., Dennett, X., Christodoulou, J. Mitochondrial electron transport chain defect presenting as hypoglycemia. J. Pediat. 130: 431-436, 1997. [PubMed: 9063420] [Full Text: https://doi.org/10.1016/s0022-3476(97)70206-3]
Kenmochi, N., Suzuki, T., Uechi, T., Magoori, M., Kuniba, M., Higa, S., Watanabe, K., Tanaka, T. The human mitochondrial ribosomal protein genes: mapping of 54 genes to the chromosomes and implications for human disorders. Genomics 77: 65-70, 2001. [PubMed: 11543634] [Full Text: https://doi.org/10.1006/geno.2001.6622]
Koc, E. C., Burkhart, W., Blackburn, K., Moseley, A., Spremulli, L. L. The small subunit of the mammalian mitochondrial ribosome: identification of the full complement of ribosomal proteins present. J. Biol. Chem. 276: 19363-19374, 2001. [PubMed: 11279123] [Full Text: https://doi.org/10.1074/jbc.M100727200]
Menezes, M. J., Guo, Y., Zhang, J., Riley, L. G., Cooper, S. T., Thorburn, D. R., Li, J., Dong, D., Li, Z., Glessner, J., Davis, R. L., Sue, C. M., Alexander, S. I., Arbuckle, S., Kirwan, P., Keating, B. J., Xu, X., Hakonarson, H., Christodoulou, J. Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia. Hum. Molec. Genet. 24: 2297-2307, 2015. [PubMed: 25556185] [Full Text: https://doi.org/10.1093/hmg/ddu747]