COX6A2
Chr 16ARcytochrome c oxidase subunit 6A2
Also known as: COX6AH, COXVIAH, COXVIa-M, MC4DN18
The COX6A2 protein is a structural subunit of cytochrome c oxidase (complex IV) that is specifically expressed in heart and skeletal muscle, where it contributes to the assembly and stabilization of this terminal enzyme in the mitochondrial respiratory chain. Mutations cause autosomal recessive mitochondrial complex IV deficiency, presenting as a multisystem disorder affecting high-energy demanding tissues including muscle, heart, brain, and liver. Clinical manifestations typically include myopathy, cardiomyopathy, developmental delays, and metabolic acidosis with variable age of onset from infancy to childhood.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
COX6A2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools