COQ2

Chr 4ADAR

coenzyme Q2, polyprenyltransferase

Also known as: CL640, COQ10D1, MSA1, PHB:PPT

NCBI Gene: 27235ENSG00000173085UniProt: Q96H96

This gene encodes an enzyme that functions in the final steps in the biosynthesis of CoQ (ubiquinone), a redox carrier in the mitochondrial respiratory chain and a lipid-soluble antioxidant. This enzyme, which is part of the coenzyme Q10 pathway, catalyzes the prenylation of parahydroxybenzoate with an all-trans polyprenyl group. Mutations in this gene cause coenzyme Q10 deficiency, a mitochondrial encephalomyopathy, and also COQ2 nephropathy, an inherited form of mitochondriopathy with primary renal involvement. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

{Multiple system atrophy, susceptibility to}MIM #146500
ADAR
Coenzyme Q10 deficiency, primary, 1MIM #607426
AR
517
ClinVar variants
36
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COQ2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 130 VUS of 517 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.
0.89LOEUF
pLI 0.001
Z-score 1.88
OE 0.47 (0.27–0.89)
Tolerant

Typical tolerance to LoF variation

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.
-0.03Z-score
OE missense 1.01 (0.89–1.13)
194 obs / 192.9 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.0.47 (0.27–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.89–1.13)
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.1.18
0≤1.21.6
LoF obs/exp: 7 / 14.8Missense obs/exp: 194 / 192.9Syn Z: -1.21

ClinVar Variant Classifications

517 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic19
VUS130
Likely Benign105
Benign11
Conflicting12
17
Pathogenic
19
Likely Pathogenic
130
VUS
105
Likely Benign
11
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
11
0
17
Likely Pathogenic
10
5
4
0
19
VUS
1
122
7
0
130
Likely Benign
0
0
33
72
105
Benign
0
1
10
0
11
Conflicting
—12
Total171286572294

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

View in ClinVar →

Protein Context — Lollipop Plot

COQ2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COQ2-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

{Multiple system atrophy, susceptibility to}

MIM #146500

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Coenzyme Q10 deficiency, primary, 1

MIM #607426

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variation of the clinical spectrum and genotype-phenotype associations in Coenzyme Q10 deficiency associated glomerulopathy.
Drovandi S et al.·Kidney Int
2022
Association of the COQ2 V393A Variant with Parkinson's Disease: A Case-Control Study and Meta-Analysis.
Yang X et al.·PLoS One
2015Meta-analysis
Iatrogenic myopathies.
Mastaglia FL·Curr Opin Neurol
2010Review
COQ2 V393A confers high risk susceptibility for multiple system atrophy in East Asian population.
Porto KJ et al.·J Neurol Sci
2021Meta-analysis
[Clinical analysis of one infantile nephrotic syndrome caused by COQ2 gene mutation and literature review].
Xu K et al.·Zhonghua Er Ke Za Zhi
2018Review
4-Hydroxybenzoic acid rescues multisystemic disease and perinatal lethality in a mouse model of mitochondrial disease.
Corral-Sarasa J et al.·Cell Rep
2024Functional
Association of the COQ2 V393A variant with risk of multiple system atrophy in East Asians: a case-control study and meta-analysis of the literature.
Zhao Q et al.·Neurol Sci
2016Meta-analysis
Human CoQ10 deficiencies.
Quinzii CM et al.·Biofactors
2008
Atypical parkinsonism - new advances.
Stamelou M et al.·Curr Opin Neurol
2016Review
COQ2 variants in Parkinson's disease and multiple system atrophy.
Mikasa M et al.·J Neural Transm (Vienna)
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Case Report: Pediatric nephrology-expanding the genotypic spectrum of COQ2-related nephropathy with a novel splice site variant in CoQ10-responsive SRNS.
Huang YR et al.·Front Med (Lausanne)
2026🔓 Open AccessCase report
Fetal Anemia and Periventricular Hyperechogenicity/Halo as a Prenatal Indicator of CoQ10 Deficiency Associated With Biallelic Variant in COQ2 Gene.
Sharma S et al.·Prenat Diagn
2025
Preclinical and first-in-human evidence of 4-hydroxybenzoic acid for mitochondrial COQ2 deficiency.
Distelmaier F et al.·Brain
2025
Prenatal Diagnosis of COQ2 Variants in Suspected Coenzyme Q10 Deficiency.
Feng Z et al.·Kidney Int Rep
2025🔓 Open Access
Functional Testing of Human Disease Missense Variants in Caenorhabditis elegans by Targeting COQ2 Variants.
Lee GY et al.·Kidney Int Rep
2025🔓 Open AccessFunctional
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