COQ7

Chr 16AR

coenzyme Q7, hydroxylase

Also known as: CAT5, COQ10D8, HMNR9

NCBI Gene: 10229 ENSG00000167186 UniProt: Q99807 OMIM: 601683

This gene encodes a mitochondrial hydroxylase that catalyzes a key step in coenzyme Q10 (ubiquinone) biosynthesis and helps stabilize the COQ enzyme complex. Autosomal recessive mutations cause primary coenzyme Q10 deficiency type 8 and distal hereditary motor neuronopathy type 9, affecting mitochondrial function and peripheral motor neurons. The gene is highly intolerant to loss-of-function variants (pLI near 1.0), suggesting complete loss of function may be embryonic lethal, while hypomorphic variants likely underlie the observed recessive phenotypes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is similar to a mitochondrial di-iron containing hydroxylase in Saccharomyces cerevisiae that is involved with ubiquinone biosynthesis. Mutations in the yeast gene lead to slower development and longer life span. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.492 OMIM phenotypes

Clinical Summary— COQ7

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Gene-Disease Validity (ClinGen)

distal hereditary motor neuropathy · ARStrong

Strong evidence — appropriate for clinical testing

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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

13 unique Pathogenic / Likely Pathogenic· 110 VUS of 256 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — COQ7

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?

1.49LOEUF

pLI 0.000

Z-score 0.42

OE 0.86 (0.52–1.49)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.46Z-score

OE missense 1.11 (0.97–1.27)

153 obs / 137.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.52–1.49)

0≤0.351.4

Missense OE?1.11 (0.97–1.27)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 9 / 10.5Missense obs/exp: 153 / 137.7Syn Z: -0.28

This gene — mechanism propensity

0.7325th %ile

GOF

0.6639th %ile

LOF

0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic5

VUS110

Likely Benign93

Benign21

Conflicting11

Pathogenic

Likely Pathogenic

110

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	6	0	0	8
Likely Pathogenic	4	1	0	0	5
VUS	11	86	12	1	110
Likely Benign	1	4	48	40	93
Benign	0	4	15	2	21
Conflicting	—				11
Total	18	101	75	43	248

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap COQ7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →