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COX17 and cytochrome-c oxidase deficiency disease

The genetic investigations in cohorts of patients with cytochrome-c oxidase deficiency, including those with hypertrophic cardiomyopathy (PMID:12538779, PMID:14681757), have not yielded verified pathogenic variants in COX17. Although several studies screened 30 probands without detecting deleterious COX17 mutations, the clinical phenotype overlaps with the broader spectrum of cytochrome-c oxidase deficiency disease, emphasizing the complexity of its genetic etiology.

In contrast, multiple functional studies provide compelling evidence for the biological importance of COX17 in mitochondrial copper delivery and cytochrome c oxidase assembly. Detailed mutational analyses and biochemical assays (PMID:11027508, PMID:10970896, PMID:15229189) demonstrate that alterations in critical residues disrupt copper trafficking, thereby impairing enzyme assembly. While the genetic data remain limited, the experimental findings support an essential role for COX17 in the molecular pathogenesis of cytochrome-c oxidase deficiency. Key take‑home sentence: Functional evidence for COX17 underscores its diagnostic utility in understanding and potentially managing cytochrome-c oxidase deficiency disease.

References

  • Pediatric research • 2003 • Mutation screening in patients with isolated cytochrome c oxidase deficiency PMID:12538779
  • Neuropediatrics • 2003 • Genotypes and clinical phenotypes in children with cytochrome-c oxidase deficiency PMID:14681757
  • Biochemical and biophysical research communications • 2000 • Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency PMID:11027508
  • The Journal of biological chemistry • 2000 • Mutational analysis of the mitochondrial copper metallochaperone Cox17 PMID:10970896
  • Human molecular genetics • 2004 • Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase PMID:15229189
  • The Journal of biological chemistry • 2008 • Mapping the functional interaction of Sco1 and Cox2 in cytochrome oxidase biogenesis PMID:18390903

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

No verified pathogenic COX17 variants have been identified in probands (PMID:12538779); however, its biological role in copper delivery supports a contributory role in disease pathogenesis.

Genetic Evidence

Limited

Screening studies involving 30 patients with COX deficiency did not reveal deleterious mutations in COX17 (PMID:12538779, PMID:14681757).

Functional Evidence

Moderate

Multiple functional assays and mutational analyses demonstrate that COX17 is essential for mitochondrial copper delivery and cytochrome c oxidase assembly (PMID:11027508, PMID:10970896, PMID:15229189).