COX10

Chr 17AR

cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10

The protein encodes heme A:farnesyltransferase, which is essential for the maturation of the heme A prosthetic group required for functional cytochrome c oxidase (complex IV) assembly. Biallelic mutations cause mitochondrial complex IV deficiency, nuclear type 3, inherited in an autosomal recessive pattern. The disease predominantly results from loss-of-function mutations that impair the enzyme's ability to process heme A, leading to defective complex IV assembly and mitochondrial respiratory chain dysfunction.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.611 OMIM phenotype
Clinical SummaryCOX10
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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)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📖
GeneReview available — COX10
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.61LOEUF
pLI 0.084
Z-score 2.73
OE 0.29 (0.150.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.18Z-score
OE missense 1.03 (0.931.14)
266 obs / 257.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.29 (0.150.61)
00.351.4
Missense OE1.03 (0.931.14)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 5 / 17.2Missense obs/exp: 266 / 257.9Syn Z: -1.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOX10-related Leigh syndromeOTHERAR

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

DN
0.74top 25%
GOF
0.5856th %ile
LOF
0.3161th %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

COX10 · 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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