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8.A.174.  The Cytochrome c Oxidase COX15 Assembly Protein (COX15) Family 

The human Cox15 protein is 410 aas long with 7 or 8 TMSs in a 1 + 2 + 2 + 2 or 3 TMS arrangement.  It is involved in step 1 of the subpathway that synthesizes heme A from heme O. This subpathway is part of the pathway heme A biosynthesis, which is itself part of Porphyrin-containing compound metabolism pathway. The cytochrome c-oxidase (COX) enzyme, mitochondrial complex IV (MT-C4D), is a transmembrane protein complex found in mitochondria. COX deficiency is one of the most frequent causes of electron transport chain defects in humans. High energy demand organs and tissues are affected in patients with mutations in the COX15 gene, with variable phenotypic expressiveness. Galvão de Oliveira et al. 2021 described a male newborn with hypertrophic cardiomyopathy and serumn and cerebrospinal fluid hyperlacticaemia, whose exome sequencing revealed two variants in a compound heterozygous state: c.232G > A; p.(Gly78Arg), classified as likely pathogenic, and c.452C > G; p.(Ser151Ter), as pathogenic.

References associated with 8.A.174 family:

Galvão de Oliveira, M., C. Tengan, C. Micheletti, P. Ramos de Macedo, M.C. Soares Pinho Cernach, T.R. Cavole, M. de França Basto, J.S. Filho, L.A. Virmond, F. Milanezi, V. Nakano, A. Falconi, and E. Perrone. (2021). A novel variant in the COX15 gene causing a fatal infantile cardioencephalomyopathy: A case report with clinical and molecular review. Eur J Med Genet 64: 104195. 33746038