COQ8A

Chr 1AR

coenzyme Q8A

Also known as: ADCK3, ARCA2, CABC1, COQ10D4, COQ8, SCAR9

NCBI Gene: 56997 ENSG00000163050 UniProt: Q8NI60 OMIM: 606980

The protein functions as an atypical kinase essential for coenzyme Q (ubiquinone) biosynthesis, which is required for mitochondrial electron transport and aerobic cellular respiration. Mutations cause primary coenzyme Q10 deficiency type 4, inherited in an autosomal recessive pattern. The pathogenic mechanism involves gain-of-function effects that disrupt normal coenzyme Q biosynthesis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a mitochondrial protein similar to yeast ABC1, which functions in an electron-transferring membrane protein complex in the respiratory chain. It is not related to the family of ABC transporter proteins. Expression of this gene is induced by the tumor suppressor p53 and in response to DNA damage, and inhibiting its expression partially suppresses p53-induced apoptosis. Alternatively spliced transcript variants have been found; however, their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.011 OMIM phenotype

Clinical Summary— COQ8A

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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

113 unique Pathogenic / Likely Pathogenic· 297 VUS of 826 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — COQ8A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.01LOEUF

pLI 0.000

Z-score 1.53

OE 0.69 (0.49–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.87Z-score

OE missense 1.12 (1.04–1.21)

448 obs / 399.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.69 (0.49–1.01)

0≤0.351.4

Missense OE?1.12 (1.04–1.21)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 20 / 28.9Missense obs/exp: 448 / 399.0Syn Z: -2.76

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCOQ8A-related coenzyme Q10 deficiencyLOFAR

This gene — mechanism propensity

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

0.6746th %ile

GOF

0.6541th %ile

LOF

0.3358th %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

826 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic52

Likely Pathogenic61

VUS297

Likely Benign283

Benign46

Conflicting72

Pathogenic

Likely Pathogenic

297

VUS

283

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	40	8	4	0	52
Likely Pathogenic	33	26	2	0	61
VUS	8	244	40	5	297
Likely Benign	0	11	131	141	283
Benign	0	0	39	7	46
Conflicting	—				72
Total	81	289	216	153	811

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap COQ8A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →