COQ4

Chr 9AR

coenzyme Q4

Also known as: CGI-92, COQ10D7, SPAX10

NCBI Gene: 51117ENSG00000167113UniProt: Q9Y3A0

This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Primary Disease Associations & Inheritance

Coenzyme Q10 deficiency, primary, 7MIM #616276
AR
Spastic ataxia 10, autosomal recessiveMIM #620666
AR
391
ClinVar variants
83
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COQ4
🧬
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.
📋
ClinVar Variants
83 Pathogenic / Likely Pathogenic· 125 VUS of 391 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.
1.58LOEUF
pLI 0.000
Z-score -0.01
OE 1.00 (0.65–1.58)
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.
0.36Z-score
OE missense 0.92 (0.81–1.05)
157 obs / 170.4 exp
Tolerant

Mild missense constraint

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.1.00 (0.65–1.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.05)
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: 13 / 13.0Missense obs/exp: 157 / 170.4Syn Z: -1.24

ClinVar Variant Classifications

391 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic22
VUS125
Likely Benign154
Benign14
Conflicting15
61
Pathogenic
22
Likely Pathogenic
125
VUS
154
Likely Benign
14
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
11
43
0
61
Likely Pathogenic
11
7
3
1
22
VUS
1
107
14
3
125
Likely Benign
0
14
66
74
154
Benign
0
4
10
0
14
Conflicting
—15
Total1914313678391

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

View in ClinVar →

Protein Context — Lollipop Plot

COQ4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COQ4-related coenzyme Q10 deficiency, primary

strong
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 Q4; COQ4
MIM #612898 · *

Coenzyme Q10 deficiency, primary, 7

MIM #616276

Molecular basis of disorder known

Autosomal recessive

Spastic ataxia 10, autosomal recessive

MIM #620666

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COQ4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biallelic COQ4 Variants in Hereditary Spastic Paraplegia: Clinical and Molecular Characterization.
Lin X et al.·Mov Disord
2024
Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes.
Laugwitz L et al.·J Med Genet
2022
Clinical features and genotype in COQ4 associated hereditary spastic paraplegia: a case report and a literature reanalysis.
Yu Z et al.·Neurol Sci
2025Review
Bi-Allelic COQ4 Variants Cause Adult-Onset Ataxia-Spasticity Spectrum Disease.
Cordts I et al.·Mov Disord
2022
Clinical phenotype, in silico and biomedical analyses, and intervention for an East Asian population-specific c.370G>A (p.G124S) COQ4 mutation in a Chinese family with CoQ10 deficiency-associated Leigh syndrome.
Lu M et al.·J Hum Genet
2019
New pathogenic variants in COQ4 cause ataxia and neurodevelopmental disorder without detectable CoQ(10) deficiency in muscle or skin fibroblasts.
Mero S et al.·J Neurol
2021
Genotype variability in early-onset Hereditary Spastic Paraplegia: a single-center study.
Colona VL et al.·Eur J Paediatr Neurol
2025
Biallelic variants in the COQ4 gene caused hereditary spastic paraplegia predominant phenotype.
Wei Q et al.·CNS Neurosci Ther
2024
Epilepsy and Coenzyme Q10 deficiency with COQ4 variants.
Hsu CJ et al.·Epilepsy Behav
2023Case report
Genetic bases and clinical manifestations of coenzyme Q10 (CoQ 10) deficiency.
Desbats MA et al.·J Inherit Metab Dis
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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