COQ6

protein-coding

coenzyme Q6, monooxygenase

Gene summary

The protein encoded by this gene belongs to the ubiH/COQ6 family. It is an evolutionarily conserved monooxygenase required for the biosynthesis of coenzyme Q10 (or ubiquinone), which is an essential component of the mitochondrial electron transport chain, and one of the most potent lipophilic antioxidants implicated in the protection of cell damage by reactive oxygen species. Knockdown of this gene in mouse and zebrafish results in decreased growth due to increased apoptosis. Mutations in this gene are associated with autosomal recessive coenzyme Q10 deficiency-6 (COQ10D6), which manifests as nephrotic syndrome with sensorineural deafness. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2012]

MANE transcript

NM_182476.3

Inheritance

AD, AR

ClinVar variants

P:37U:168B:78

Top phenotype

Coenzyme Q10 deficiency, primary 6

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr14:73,949,926-73,963,670

External References & Databases

Ensembl (ENSG00000119723)

Transcript & Mutation Effects

hg38 • Region Span ~13.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

SMARCB1-related schwannomatosisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0024517

Submitter: Ambry Genetics

familial steroid-resistant nephrotic syndrome with sensorineural deafnessSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013836

Submitter: Labcorp Genetics (formerly Invitae)

familial steroid-resistant nephrotic syndrome with sensorineural deafnessSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013836

Submitter: Orphanet

familial steroid-resistant nephrotic syndrome with sensorineural deafnessMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013836

Submitter: Ambry Genetics

primary coenzyme Q10 deficiency 8DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014754

Submitter: ClinGen

COQ6 was first reported in relation to autosomal recessive COQ10 deficiency in 2011 by Heeringa et al. (PMID: 21540551). This condition typically manifests in infancy and shows significantly progressive kidney disease leading to end-stage renal failure and often hearing loss. Probands typically have focal segmental glomerulosclerosis. 19 variants (missense, in-frame deletion, nonsense, frameshift, splicing) that have been reported in at least 30 probands in 8 publications (PMIDs: 21540551, 25349199, 28117207, 30232548, 31130284, 31328266, 35111204, 35483523) are included in this curation. The maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (expression and functional alteration evidence; PMIDs: 21540551). Expression data in mouse and rat samples indicates expression in podocyte cellular processes and Golgi. Downregulation of COQ6 is associated with increased apoptosis in mice, a phenotype reduced via COQ10 administration. Knockdown of the protein in zebrafish led to increased apoptosis in the head and trunk. In summary, there is definitive evidence supporting the relationship between COQ6 and autosomal recessive COQ10 deficiency. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Glomerulopathy GCEP on the meeting date 4/14/25 (SOP Version 11).

Clinical Genomic Database (CGD)

Coenzyme Q10 deficiency, primary 6AR

Manifestation: Biochemical; Musculoskeletal; Neurologic; Renal

Intervention: Biochemical

Rationale: Some patients have been reported as showing a favorable response to oral Coenzyme Q supplementation

Refs: 21540551

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COQ6 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 249

Familial steroid-resistant nephrotic syndrome with sensorineural deafnessTotal: 107

Inborn genetic diseasesTotal: 64

COQ6-related disorderTotal: 19

not specifiedTotal: 16

increased susceptibility to pneumoniaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182476.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	66 clinvar		67
missense	2 clinvar	5 clinvar	162 clinvar	9 clinvar	3 clinvar	181
nonsense	6 clinvar	5 clinvar	1 clinvar			12
start loss			1 clinvar			1
frameshift	9 clinvar	6 clinvar	2 clinvar			17
splice donor/acceptor (+/-2bp)		4 clinvar	1 clinvar			5
Total	17	20	168	75	3	283

Highest pathogenic variant AF is 0.00009355093

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 73 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182476.3	RefSeq	NP_872282.1	12	MANE Select
ENST00000334571.7	Ensembl	ENSP00000333946.2	12	MANE Select
NM_001425255.1	RefSeq	NP_001412184.1	11	Standard
NM_001425256.1	RefSeq	NP_001412185.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
coq6	Danio rerio	Structure: apoptotic process Quality: increased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

coq6

Danio rerio

Structure: apoptotic process

Quality: increased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquinone and other terpenoid-quinone biosynthesis - Homo sapiens (human)
Ubiquinone Biosynthesis
Metabolism
Ubiquinol biosynthesis
Metabolism of cofactors

Biological Process

ubiquinone biosynthetic process
oxidation-reduction process

Molecular Function

protein binding
oxidoreductase activity
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
FAD binding

Cellular Component

mitochondrion
Golgi apparatus
extrinsic component of mitochondrial inner membrane
cell projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334571
Coding exons: 12
Length: 13745
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125748
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.618	232	260	0.892	0.0000149	3041
Missense (PolyPhen)		79	93.187	0.84776		1117
Synonymous	1.25	89	105	0.845	0.00000673	952
Loss of Function	0.286	23	24.5	0.938	0.00000135	270

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.00075	0.00075	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: FAD-dependent monooxygenase required for the C5-ring hydroxylation during ubiquinone biosynthesis. Catalyzes the hydroxylation of 3-polyprenyl-4-hydroxybenzoic acid to 3- polyprenyl-4,5-dihydroxybenzoic acid. The electrons required for the hydroxylation reaction may be funneled indirectly from NADPH via a ferredoxin/ferredoxin reductase system to COQ6. {ECO:0000255|HAMAP-Rule:MF_03193}.;
Disease: DISEASE: Note=Mutations in COQ6 may play a role in susceptibility to Schwannomatosis, a cancer predisposition syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves. {ECO:0000269|PubMed:24763291}.;

Recessive Scores

pRec: 0.220

Intolerance Scores

LoFtool: 0.849
RVIS EVS: 0.71
RVIS percentile EVS: 85.68

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.892

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	Medium
Primary Immunodeficiency	High	High	High
Cancer	High	High	High