COQ4

Chr 9AR

coenzyme Q4

Also known as: CGI-92, COQ10D7, SPAX10

NCBI Gene: 51117 ENSG00000167113 UniProt: Q9Y3A0 OMIM: 612898

The protein functions as a lyase that catalyzes C1-decarboxylation of 4-hydroxy-3-methoxy-5-(all-trans-decaprenyl)benzoic acid to 2-methoxy-6-(all-trans-decaprenyl)phenol during ubiquinone biosynthesis. Autosomal recessive mutations cause primary coenzyme Q10 deficiency type 7 and spastic ataxia 10 through disruption of the coenzyme Q10 biosynthetic pathway. Loss of function mutations result in cellular energy defects due to impaired mitochondrial electron transport chain function.

GeneReviews OMIM ResearchSummary from OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.582 OMIM phenotypes

Clinical Summary— COQ4

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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

44 unique Pathogenic / Likely Pathogenic· 122 VUS of 356 total submissions

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GeneReview available — COQ4

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.36Z-score

OE missense 0.92 (0.81–1.05)

157 obs / 170.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.00 (0.65–1.58)

0≤0.351.4

Missense OE?0.92 (0.81–1.05)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 13 / 13.0Missense obs/exp: 157 / 170.4Syn Z: -1.24

ClinVar Variant Classifications

356 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23

Likely Pathogenic21

VUS122

Likely Benign154

Benign14

Conflicting15

Pathogenic

Likely Pathogenic

122

VUS

154

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	11	0	0	23
Likely Pathogenic	14	7	0	0	21
VUS	3	108	8	3	122
Likely Benign	1	14	66	73	154
Benign	0	4	10	0	14
Conflicting	—				15
Total	30	144	84	76	349

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap COQ4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →