HGNC Approved Gene Symbol: MRPS25
Cytogenetic location: 3p25.1 Genomic coordinates (GRCh38): 3:15,042,251-15,065,315 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3p25.1 | ?Combined oxidative phosphorylation deficiency 50 | 619025 | Autosomal recessive | 3 |
The MRPS25 gene encodes a structural component of the mitochondrial 28S ribosome, which plays a role in translation of mitochondrial proteins (summary by Bugiardini et al., 2019).
Mitochondria have their own translation system for production of 13 proteins essential for oxidative phosphorylation. MRPS25 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 MRPS25. The deduced 151-amino acid MRPS25 protein has a calculated molecular mass of 17.7 kD. Koc et al. (2001) identified MRPS25 orthologs in mouse, Drosophila, C. elegans, and yeast, but not in E. coli. Mouse and human MRPS25 share 89.5% amino acid identity.
By radiation hybrid analysis and analysis of an integrated BAC-STS map, Kenmochi et al. (2001) mapped the MRPS25 gene to chromosome 3p25.
In a 25-year-old man with combined oxidative phosphorylation deficiency-50 (COXPD50; 619025), Bugiardini et al. (2019) identified a homozygous missense mutation in the MRPS25 gene (P72L; 611987.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient fibroblasts showed decreased protein levels of MRPS25, about one-tenth of controls. Levels of other polypeptides of the 28S ribosomal subunit were also decreased, suggesting that the mutation adversely affected assembly or stability of the 28S subunit. Further in vitro studies of patient fibroblasts showed impaired mitochondrial translation and decreased protein levels of respiratory chain complexes I, III, and IV. Expression of wildtype MRPS25 in patient fibroblasts resulted in partial restoration of OXPHOS protein levels. The findings suggested that MRPS25 is required for mitochondrial protein synthesis, and that this defect causes decreased levels of mitochondrial respiratory chain subunits and impaired mitochondrial translation.
In a 25-year-old man with combined oxidative phosphorylation deficiency-50 (COXPD50; 619025), Bugiardini et al. (2019) identified a homozygous c.215C-T transition in the MRPS25 gene, resulting in a pro72-to-leu (P72L) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was absent from the Exome Sequencing Project database and was present in heterozygous state at a low frequency in the gnomAD database (MAF, 0.000008). Patient fibroblasts showed decreased protein levels of MRPS25, about one-tenth of controls. Levels of other polypeptides of the 28S subunit were also decreased, suggesting that the mutation adversely affects assembly or stability of the 28S subunit. Further in vitro studies of patient fibroblasts showed impaired mitochondrial translation and decreased protein levels of respiratory chain complexes I, III, and IV. Expression of wildtype MRPS25 in patient fibroblasts resulted in partial restoration of OXPHOS protein levels. The findings suggested that MRPS25 is required for mitochondrial protein synthesis, and that this defect causes decreased levels of mitochondrial respiratory chain subunits and impaired mitochondrial translation.
Bugiardini, E., Mitchell, A. L., Dalla Rosa, I., Horning-Do, H.-T., Pitmann, A. M., Poole, O. V., Holton, J. L., Shah, S., Woodward, C., Hargreaves, I., Quinlivan, R., Amunts, A., Wiesner, R. J., Houlden, H., Holt, I. J., Hanna, M. G., Pitceathly, R. D. S., Spinazzola, A. MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy. Hum. Molec. Genet. 28: 2711-2719, 2019. [PubMed: 31039582] [Full Text: https://doi.org/10.1093/hmg/ddz093]
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]