COA8

Chr 14AR

cytochrome c oxidase assembly factor 8

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

NCBI Gene: 84334 ENSG00000256053 UniProt: Q96IL0 OMIM: 616003

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that localizes to the mitochondria, where it stimulates the release of cytochrome c, thereby promoting programmed cell death. Mutations in this gene have been found in individuals with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.251 OMIM phenotype

Clinical Summary— COA8

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 81 VUS of 218 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.25LOEUF

pLI 0.000

Z-score 1.00

OE 0.67 (0.38–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.50Z-score

OE missense 1.14 (0.98–1.33)

114 obs / 100.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.67 (0.38–1.25)

0≤0.351.4

Missense OE?1.14 (0.98–1.33)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

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

This gene — mechanism propensity

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

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

218 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic8

VUS81

Likely Benign72

Benign26

Conflicting7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	1	1	0	8
Likely Pathogenic	8	0	0	0	8
VUS	4	57	18	2	81
Likely Benign	1	4	46	21	72
Benign	0	5	20	1	26
Conflicting	—				7
Total	19	67	85	24	202

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

55 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap COA8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →