COX18
Chr 4ARcytochrome c oxidase assembly factor COX18
Also known as: CMT2MM, COX18HS, MC4DN25, OXA1L2
This gene encodes a mitochondrial membrane insertase that translocates cytochrome c oxidase subunit II across the mitochondrial inner membrane and is essential for respiratory chain complex IV assembly and stability. Mutations cause autosomal recessive mitochondrial complex IV deficiency and Charcot-Marie-Tooth disease type 2MM, an axonal peripheral neuropathy. The gene appears relatively tolerant to loss-of-function variants based on constraint metrics.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
105 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 2 | 23 | 0 | 25 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 2 | 54 | 6 | 0 | 62 |
Likely Benign | 1 | 4 | 1 | 0 | 6 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 3 | 60 | 32 | 0 | 95 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
COX18 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools