COQ2

Chr 4ADAR

coenzyme Q2, polyprenyltransferase

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

NCBI Gene: 27235 ENSG00000173085 UniProt: Q96H96 OMIM: 609825

COQ2 encodes an enzyme that catalyzes the prenylation of para-hydroxybenzoate in the biosynthesis of coenzyme Q10, which functions as an electron carrier in the mitochondrial respiratory chain and as a lipid-soluble antioxidant. Mutations cause primary coenzyme Q10 deficiency, a mitochondrial disorder that can present as encephalomyopathy or nephropathy with primary renal involvement. The gene shows both autosomal recessive and autosomal dominant inheritance patterns.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.892 OMIM phenotypes

Clinical Summary— COQ2

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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

40 unique Pathogenic / Likely Pathogenic· 201 VUS of 474 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — COQ2

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?

0.89LOEUF

pLI 0.001

Z-score 1.88

OE 0.47 (0.27–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.03Z-score

OE missense 1.01 (0.89–1.13)

194 obs / 192.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.47 (0.27–0.89)

0≤0.351.4

Missense OE?1.01 (0.89–1.13)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 7 / 14.8Missense obs/exp: 194 / 192.9Syn Z: -1.21

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCOQ2-related coenzyme Q10 deficiencyLOFAR

This gene — mechanism propensity

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

0.77top 25%

GOF

0.5954th %ile

LOF

0.3066th %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

474 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic29

VUS201

Likely Benign176

Benign23

Conflicting27

Pathogenic

Likely Pathogenic

201

VUS

176

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	1	0	0	11
Likely Pathogenic	20	9	0	0	29
VUS	6	188	7	0	201
Likely Benign	1	4	58	113	176
Benign	0	3	18	2	23
Conflicting	—				27
Total	37	205	83	115	467

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap COQ2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →