COX15

Chr 10AR

cytochrome c oxidase assembly factor COX15

Also known as: CEMCOX2, HAS, MC4DN6

The protein functions in the biogenesis of cytochrome c oxidase (complex IV) and is involved in the hydroxylation of heme O, which is essential for proper assembly of this terminal component of the mitochondrial respiratory chain. Mutations cause mitochondrial complex IV deficiency through an autosomal recessive inheritance pattern, resulting in impaired cellular respiration. The pathogenic mechanism involves loss of function leading to defective complex IV assembly and subsequent mitochondrial dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.331 OMIM phenotype
Clinical SummaryCOX15
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.000
Z-score 0.35
OE 0.92 (0.651.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.26Z-score
OE missense 0.95 (0.851.07)
208 obs / 218.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.92 (0.651.33)
00.351.4
Missense OE0.95 (0.851.07)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 21 / 22.8Missense obs/exp: 208 / 218.9Syn Z: -0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOX15-related Leigh syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.5170th %ile
LOF
0.4136th %ile

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COX15 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC