Features include always present findings: Encephalopathy, Elevated brain lactate level by MRS, Hypoglycemia, and Feeding difficulties in infancy and others; and common findings: Elevated creatine kinase (muscle enzyme) (elevated circulating creatine kinase concentration), Hepatic failure, Abnormality of the coagulation cascade, and Elevated circulating dodecanoylcarnitine concentration and others.

COX16 encodes cytochrome c oxidase assembly factor COX16 (106 aa). Required for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. Highest expression in Cells EBV-transformed lymphocytes (58.3 TPM) and Cells Cultured fibroblasts (54.8 TPM).

Mitochondrial complex IV deficiency, nuclear type 22 is associated with mutations in the COX16 gene on chromosome 14.

The COX16 protein participates in Metallochaperone inserts 2Cu2+ into MT-CO2 and Metallochaperone inserts Cu2+ into MT-CO1 pathways.

COX16 is classified as a druggable target with score 0.0.

Genetic testing for COX16 is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 11 always present features, 20 common features.

No clinical trials have been registered for mitochondrial complex IV deficiency, nuclear type 22.

3 publications have been identified in PubMed for mitochondrial complex IV deficiency, nuclear type 22. Research spans Basic Science / Preclinical (67%) and Gene Therapy / Novel Therapeutics (33%).

Recent Publications

• Kim TY (2026). [PMID: 41621246](https://pubmed.ncbi.nlm.nih.gov/41621246/). *Redox Biol*. [Basic Science / Preclinical]

• Campos-Ribeiro MA (2026). [PMID: 41420107](https://pubmed.ncbi.nlm.nih.gov/41420107/). *EMBO Mol Med*. [Basic Science / Preclinical]

• Ling L (2025). [PMID: 41502520](https://pubmed.ncbi.nlm.nih.gov/41502520/). *Oncol Res*. [Gene Therapy / Novel Therapeutics]