COA8

Chr 14AR

cytochrome c oxidase assembly factor 8

Also known as: APOP, APOP1, APOPT1, C14orf153, MC4DN17

COA8 encodes a mitochondrial protein required for cytochrome c oxidase (complex IV) assembly and function, protecting the assembly process from oxidation-induced degradation. Biallelic mutations cause autosomal recessive mitochondrial complex IV deficiency, which typically presents as a multi-system disorder affecting energy metabolism. The gene shows minimal constraint against loss-of-function variants (pLI 0.0002, LOEUF 1.25), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.251 OMIM phenotype
Clinical SummaryCOA8
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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
1.25LOEUF
pLI 0.000
Z-score 1.00
OE 0.67 (0.381.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.50Z-score
OE missense 1.14 (0.981.33)
114 obs / 100.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.67 (0.381.25)
00.351.4
Missense OE1.14 (0.981.33)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 7 / 10.5Missense obs/exp: 114 / 100.0Syn Z: -1.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOA8-related mitochondrial complex IV deficiencyLOFAR

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

DN
0.7326th %ile
GOF
0.5758th %ile
LOF
0.3356th %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

COA8 · 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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