COQ8A

Chr 1AR

coenzyme Q8A

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

NCBI Gene: 56997ENSG00000163050UniProt: Q8NI60

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]

Primary Disease Associations & Inheritance

Coenzyme Q10 deficiency, primary, 4MIM #612016
AR
547
ClinVar variants
101
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COQ8A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
101 Pathogenic / Likely Pathogenic· 192 VUS of 547 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.87Z-score
OE missense 1.12 (1.04–1.21)
448 obs / 399.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.49–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.04–1.21)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.27
0≤1.21.6
LoF obs/exp: 20 / 28.9Missense obs/exp: 448 / 399.0Syn Z: -2.76

ClinVar Variant Classifications

547 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic40
VUS192
Likely Benign194
Benign19
Conflicting41
61
Pathogenic
40
Likely Pathogenic
192
VUS
194
Likely Benign
19
Benign
41
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
7
32
0
61
Likely Pathogenic
20
18
2
0
40
VUS
3
147
39
3
192
Likely Benign
0
9
89
96
194
Benign
0
0
12
7
19
Conflicting
—41
Total45181174106547

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

View in ClinVar →

Protein Context — Lollipop Plot

COQ8A · protein map & ClinVar variants

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

Gene2Phenotype Curations

COQ8A-related coenzyme Q10 deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
COENZYME Q8A; COQ8A
MIM #606980 · *

Coenzyme Q10 deficiency, primary, 4

MIM #612016

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COQ8A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review.
Galosi S et al.·Parkinsonism Relat Disord
2019Review
Mitochondrial Dysfunction due to Novel COQ8A Variation with Poor Response to CoQ10 Treatment: A Comprehensive Study and Review of Literatures.
Wang J et al.·Cerebellum
2024Review
The cerebellar bioenergetic state predicts treatment response in COQ8A-related ataxia.
Prasuhn J et al.·Parkinsonism Relat Disord
2022
Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients.
Traschütz A et al.·Ann Neurol
2020Cohort
Genetic Dystonias: Update on Classification and New Genetic Discoveries.
Keller Sarmiento IJ et al.·Curr Neurol Neurosci Rep
2021Review
A novel COQ8A missense variant associated with a mild form of primary coenzyme Q10 deficiency type 4.
Liu G et al.·Clin Biochem
2020Case report
Childhood-onset autosomal recessive ataxias: a cross-sectional study from Turkey.
Mutlu-Albayrak H et al.·Neurogenetics
2020
Primary coenzyme Q10 deficiency due to COQ8A gene mutations.
Zhang L et al.·Mol Genet Genomic Med
2020Case report
Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function.
Vazquez Fonseca L et al.·Hum Mutat
2018Cohort
Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients.
Traschütz A et al.·Ann Neurol
2023Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Intermittent ketogenic fasting with medium-chain triglycerides improves ataxia in COQ8A-related coenzyme Q10 deficiency: A case report.
Hahn W et al.·Mol Genet Metab Rep
2026🔓 Open AccessCase report
Coenzyme Q10 Supplementation in a Child with Biallelic COQ8A Variants: A Case Report.
Motoi H et al.·Case Rep Neurol
2026🔓 Open AccessCase report
Case Report: Myoclonic and tremulous movements associated with COQ8A-related coenzyme Q10 deficiency type 4.
Wang D et al.·Front Genet
2025🔓 Open AccessCase report
Adult-onset status epilepticus in patients with COQ8A coenzyme Q10 deficiency: A case series.
Tsalouchidou PE et al.·Epilepsy Behav Rep
2024🔓 Open AccessCohort
Refractory Epilepsy in Adult Patient With COQ8A Variant Improves With CoQ10 Supplementation: A Case for Exome Sequencing in the ICU.
LoVoi J et al.·Neurol Genet
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools