COX4I1
Chr 16ARcytochrome c oxidase subunit 4I1
Also known as: COX IV-1, COX4, COX4-1, COXIV, COXIV-1, MC4DN16
COX4I1 encodes subunit IV isoform 1 of cytochrome c oxidase (complex IV), the terminal enzyme of the mitochondrial electron transport chain that reduces oxygen to water and contributes to ATP production through oxidative phosphorylation. Mutations cause mitochondrial complex IV deficiency, nuclear type 16, which follows autosomal recessive inheritance. This gene has a relatively low constraint against loss-of-function variants (pLI 0.39, LOEUF 0.68), suggesting some tolerance to heterozygous loss of function.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
COX4I1 · 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