Alternative titles; symbols
HGNC Approved Gene Symbol: COX6B1
Cytogenetic location: 19q13.12 Genomic coordinates (GRCh38): 19:35,648,323-35,658,782 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19q13.12 | Mitochondrial complex IV deficiency, nuclear type 7 | 619051 | Autosomal recessive | 3 |
Taanman et al. (1989) isolated a human cDNA clone coding for subunit VIb of cytochrome c oxidase. In addition to isolating 3 processed pseudogenes that lacked introns, they isolated an intron-containing clone which they assumed represented the expressed gene.
Carrero-Valenzuela et al. (1991) isolated and sequenced a human heart cDNA coding for cytochrome c oxidase subunit VIb. The cDNA extended 50 bp upstream from the region coding for the mature peptide. By Northern analysis, a single transcript of approximately 550 nucleotides was identified in 6 human tissues. Southern analysis of human genomic DNA demonstrated the presence of multiple loci that showed high homology to the cDNA. These loci cosegregated with 5 or 6 different human chromosomes and human-rodent somatic cell hybrids. Two of these isolated loci appeared to represent pseudogenes.
By FISH analysis, Taanman et al. (1991) mapped the COX6B1 gene to chromosome 19q13.1.
Massa et al. (2008) identified a homozygous mutation in the COX6B1 gene (R19H; 124089.0001) in 2 Saudi Arabian sibs with mitochondrial complex IV deficiency nuclear type 7 (MC4DN7; 619051).
In a male child, born of consanguineous Palestinian parents, with MC4DN7, Abdulhag et al. (2015) identified a homozygous missense mutation in the COX6B1 gene (R20C; 124089.0002).
In 2 brothers, born of consanguineous Saudi Arabian parents, with cytochrome c oxidase deficiency (MC4DN7; 619051), Massa et al. (2008) identified a homozygous 221G-A transition in exon 2 of the COX6B1 gene, resulting in an arg19-to-his (R19H) substitution in a highly conserved residue and predicted to alter protein conformation. Both brothers had increased serum and CSF lactate and decreased COX activity (20% of normal) in muscle biopsy. In vitro studies showed that the mutant COX6B1 subunit resulted in a decrease of fully assembled COX.
Abdulhag et al. (2015) referred to this mutation as R20H.
In a male child, born of consanguineous Palestinian parents, with cytochrome c oxidase deficiency (MC4DN7; 619051), Abdulhag et al. (2015) identified a homozygous c.58C-T transition (c.58C-T, NM_001863.4) in the COX6B1 gene, resulting in an arg20-to-cys (R20C) substitution at a conserved residue involved in an extended network of hydrogen bonds that serve to stabilize the protein. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the Exome Variant Server database. Western blot analysis of patient muscle mitochondria showed isolated undetectable complex IV activity and barely detectable residual amount of mutant protein (11% of control), suggesting that the mutant protein is unstable. Transfection of wildtype COX6B1 into patient fibroblasts restored COX activity. Although Abdulhag et al. (2015) reported the mutation as R20C, they stated that the affected codon was the same as that reported by Massa et al. (2008) as R19H (124089.0001).
Abdulhag, U. N., Soiferman, D., Schueler-Furman, O., Miller, C., Shaag, A., Elpeleg, O., Edvardson, S., Saada, A. Mitochondrial complex IV deficiency, caused by mutated COX6B1, is associated with encephalomyopathy, hydrocephalus and cardiomyopathy. Europ. J. Hum. Genet. 23: 159-164, 2015. [PubMed: 24781756] [Full Text: https://doi.org/10.1038/ejhg.2014.85]
Carrero-Valenzuela, R. D., Quan, F., Lightowlers, R., Kennaway, N. G., Litt, M., Forte, M. Human cytochrome c oxidase subunit VIb: characterization and mapping of a multigene family. Gene 102: 229-236, 1991. [PubMed: 1651883] [Full Text: https://doi.org/10.1016/0378-1119(91)90082-m]
Massa, V., Fernandez-Vizarra, E., Alshahwan, S., Bakhsh, E., Goffrini, P., Ferrero, I., Mereghetti, P., D'Adamo, P., Gasparini, P., Zeviani, M. Severe infantile encephalomyopathy caused by a mutation in COX6B1, a nucleus-encoded subunit of cytochrome c oxidase. Am. J. Hum. Genet. 82: 1281-1289, 2008. [PubMed: 18499082] [Full Text: https://doi.org/10.1016/j.ajhg.2008.05.002]
Taanman, J.-W., Schrage, C., Ponne, N., Bolhuis, P., de Vries, H., Agsteribbe, E. Nucleotide sequence of cDNA encoding subunit VIb of human cytochrome c oxidase. Nucleic Acids Res. 17: 1766 only, 1989. [PubMed: 2537962] [Full Text: https://doi.org/10.1093/nar/17.4.1766]
Taanman, J.-W., van der Veen, A. Y., Schrage, C., de Vries, H., Buys, C. H. C. M. Assignment of the gene coding for human cytochrome c oxidase subunit VIb to chromosome 19, band q13.1, by fluorescence in situ hybridisation. Hum. Genet. 87: 325-327, 1991. [PubMed: 1650756] [Full Text: https://doi.org/10.1007/BF00200913]