HGNC Approved Gene Symbol: MRPS16
SNOMEDCT: 764943000;
Cytogenetic location: 10q22.2 Genomic coordinates (GRCh38): 10:73,248,849-73,252,644 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 10q22.2 | Combined oxidative phosphorylation deficiency 2 | 610498 | Autosomal recessive | 3 |
Mammalian mitochondria carry out the synthesis of 13 polypeptides that are essential for oxidative phosphorylation. Mitochondrial ribosomes are composed of small (28S) and large (39S) subunits. MRPS16 is a component of the small subunit, which contains a 12S rRNA (MTRNR1; 561000) and about 30 proteins. In mitochondrial ribosomes, the RNA molecules are transcribed from the mitochondrial DNA, but the ribosomal proteins, such as MRPS16, are encoded by the nuclear genome. They are synthesized in the cytoplasm and imported into the mitochondria (Kenmochi et al., 2001; Koc et al., 2001).
By proteolytic digestion of whole bovine 28S subunits, followed by peptide analysis and EST database analysis, Koc et al. (2001) identified human MRPS16. The deduced 137-amino acid protein has a calculated molecular mass of 15.3 kD. Following cleavage of the N-terminal 34-amino acid mitochondrial import signal, the mature protein has a calculated molecular mass of 11.5 kD. MRPS16 homologs were identified in mouse, Drosophila, C. elegans, yeast, and E. coli genomes. Mouse and human MRPS16 share 91.1% amino acid identity.
By radiation hybrid analysis and genomic sequence analysis, Kenmochi et al. (2001) mapped the MRPS16 gene to chromosome 10q22.1.
In a patient with combined oxidative phosphorylation deficiency (COXPD2; 610498) manifesting as agenesis of the corpus callosum, dysmorphism, and fatal neonatal lactic acidosis, Miller et al. (2004) identified a homozygous nonsense mutation in the MRPS16 gene (609204.0001), resulting in a defect in mitochondrial translation.
Koc et al. (2001) proposed that mitochondrial ribosomal proteins with prokaryotic homologs, such as MRPS16, be given the same number as the corresponding ribosomal protein in E. coli. Since there are 21 proteins in the bacterial ribosome, novel mammalian mitochondrial ribosomal proteins without prokaryotic homologs are designated MRPS22 and above.
In a patient with combined oxidative phosphorylation deficiency (610498) manifesting as agenesis of the corpus callosum, dysmorphism, and fatal neonatal lactic acidosis, Miller et al. (2004) identified a homozygous 331C-T transition in the MRPS16 gene, resulting in an arg111-to-ter (R111X) substitution. The abundance of the 12S rRNA transcript was markedly decreased to 12% of control values, which may be an indirect result of the MRPS16 mutation. The parents were consanguineous and heterozygous for the mutation.
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]
Miller, C., Saada, A., Shaul, N., Shabtai, N., Ben-Shalom, E., Shaag, A., Hershkovitz, E., Elpeleg, O. Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation. Ann. Neurol. 56: 734-738, 2004. [PubMed: 15505824] [Full Text: https://doi.org/10.1002/ana.20282]