Alternative titles; symbols
HGNC Approved Gene Symbol: MRPL12
Cytogenetic location: 17q25.3 Genomic coordinates (GRCh38): 17:81,703,367-81,707,517 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q25.3 | ?Combined oxidative phosphorylation deficiency 45 | 618951 | Autosomal recessive | 3 |
The MRPL12 gene encodes a protein of the large subunit of the mitochondrial ribosome, and thus plays a role in mitochondrial translation (summary by Serre et al., 2013).
Marty and Fort (1996) cloned a cDNA from a HeLa cell library that encodes a protein localized predominantly to the mitochondria and is homologous to bacterial and chloroplast ribosomal L12 proteins. They designated it 'mitochondrial ribosomal protein L12,' or MRPL12. The predicted 198-amino acid protein has a 49-amino acid N-terminal mitochondrial targeting sequence. Marty et al. (1997) found a single 1.2-kb mRNA transcribed primarily in colon and skeletal muscle, with lower levels in other tissues.
Marty et al. (1997) mapped the MRPL12 gene to chromosome 17q25-qter by fluorescence in situ hybridization.
In a boy, born of consanguineous Roma Gypsy parents, with combined oxidative phosphorylation deficiency-45 (COXPD45; 618951), Serre et al. (2013) identified a homozygous missense mutation in the MRPL12 gene (A181V; 602375.0001). The mutation, which was found by a combination of homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. The mutation was not found in the dbSNP database or in 100 ethnically matched controls. In a subsequent pregnancy, affected dizygotic twin fetuses were also found to carry this homozygous mutation; the pregnancy was terminated.
In a boy, born of consanguineous Roma Gypsy parents, with combined oxidative phosphorylation deficiency-45 (COXPD45; 618951), Serre et al. (2013) identified a homozygous c.542C-T transition (c.542C-T, NM_002949.3) in exon 5 of the MRPL12 gene, resulting in an ala181-to-val (A181V) substitution at a highly conserved residue. The mutation, which was found by a combination of homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. The mutation was not found in the dbSNP database or in 100 ethnically matched controls. In a subsequent pregnancy, affected dizygotic twin fetuses were also found to carry this homozygous mutation; the pregnancy was terminated. The steady-state level of MRPL12 in patient fibroblasts was reduced to 30% of control values, and there was altered integration into the large ribosomal subunit. In vitro translation studies showed a reduction in the synthesis of subunits in mitochondrial complexes I, II, and III, but no aberrant translation products were identified.
Marty, L., Fort, P. A delayed-early response nuclear gene encoding MRPL12, the mitochondrial homologue to the bacterial translational regulator L7/L12 protein. J. Biol. Chem. 271: 11468-11476, 1996. [PubMed: 8626705] [Full Text: https://doi.org/10.1074/jbc.271.19.11468]
Marty, L., Taviaux, S., Fort, P. Expression and human chromosomal localization to 17q25 of the growth-regulated gene encoding the mitochondrial ribosomal protein MRPL12. Genomics 41: 453-457, 1997. [PubMed: 9169145] [Full Text: https://doi.org/10.1006/geno.1997.4691]
Serre, V., Rozanska, A., Beinat, M., Chretien, D., Boddaert, N., Munnich, A., Rotig, A., Chrzanowska-Lightowlers, Z. M. Mutations in mitochondrial ribosomal protein MRPL12 leads to growth retardation, neurological deterioration and mitochondrial translation deficiency. Biochim. Biophys. Acta 1832: 1304-1312, 2013. [PubMed: 23603806] [Full Text: https://doi.org/10.1016/j.bbadis.2013.04.014]