COQ7

protein-coding

coenzyme Q7, hydroxylase

Gene summary

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]

MANE transcript

NM_016138.5

Inheritance

ClinVar variants

P:19U:102B:53

Top phenotype

Coenzyme Q10 deficiency, primary 8

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr16:19,067,614-19,080,095

External References & Databases

Ensembl (ENSG00000167186)

Transcript & Mutation Effects

hg38 • Region Span ~12.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary coenzyme Q10 deficiency 8MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014754

Submitter: Ambry Genetics

distal hereditary motor neuropathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018894

Submitter: ClinGen

COQ7: autosomal recessive distal hereditary motor neuropathy (dHMN) Evidence Summary: Coenzyme Q7 (COQ7) encodes a mitochondrial hydroxylase that catalyzes the penultimate step in the biosynthesis of coenzyme Q10 (CoQ10), an essential electron carrier of the mitochondrial respiratory chain required for oxidative phosphorylation and ATP production (Jacquier et al., PMID: 36454683). Pathogenic variants in COQ7 have been associated with primary CoQ10 deficiency (Freyer et al., PMID: 26084283) and distal hereditary motor neuropathy (dHMN) (Jacquier et al., PMID: 36454683; Rebelo et al., PMID: 37170631). Both primary CoQ10 deficiency and dHMN due to COQ7 biallelic variants were lumped into a single disease entity, as both phenotypes share the same autosomal recessive inheritance pattern, overlapping neurological features including motor neuropathy and upper motor neuron signs, and a common loss-of-function mechanism resulting in CoQ10 deficiency, with at least 3 shared gene variants (R54Q, R107W, I200WfsTer56). Affected individuals with dHMN and biallelic COQ7 variants present with distal motor neuropathy with pes cavus, often accompanied by upper motor neuron signs like brisk reflexes and/or Babinski sign. Evidence supporting this gene–disease relationship includes case-level data, segregation data, and experimental data from multiple independent cohorts, with multiple missense or null variants reported (Jacquier et al.; Rebelo et al.; Liu et al., PMID: 36758993; Smith et al., PMID: 37077559; Zhang et al., PMID: 37077559). Functional studies demonstrated decreased COQ7 mRNA and protein expression, impairing CoQ10 biosynthesis and mitochondrial respiration in vitro. Patient-derived iPSC motor neurons also showed reduced protein levels of COQ7 and increased levels of neurofilament light protein leakage, indicating axonal damage (Rebelo et al.). In summary, there is STRONG evidence supporting this gene-disease relationship. This classification was approved by the ClinGen Charcot-Marie-Tooth Expert Panel on the March 13 2026 (SOP Version 11).

primary coenzyme Q10 deficiency 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014754

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Coenzyme Q10 deficiency, primary 8AR

Manifestation: Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal

Intervention: Biochemical

Rationale: Treatment with coenzyme Q10 has been described as possibly beneficial

Refs: 26084283; 36454683; 36758993; 37077559

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COQ7 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 187

not specifiedTotal: 45

Primary coenzyme Q10 deficiency 8Total: 18

COQ7-related disorderTotal: 16

Neuronopathy, distal hereditary motor, autosomal recessive 9Total: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016138.5. 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			2 clinvar	40 clinvar	1 clinvar	43
missense	5 clinvar	3 clinvar	87 clinvar	11 clinvar	1 clinvar	107
nonsense		1 clinvar	3 clinvar			4
start loss	1 clinvar	2 clinvar				3
frameshift	1 clinvar	5 clinvar	6 clinvar			12
splice donor/acceptor (+/-2bp)	1 clinvar		4 clinvar			5
Total	8	11	102	51	2	174

Highest pathogenic variant AF is 0.000036938432

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016138.5	RefSeq	NP_057222.2	6	MANE Select
ENST00000321998.10	Ensembl	ENSP00000322316.5	6	MANE Select
NM_001190983.2	RefSeq	NP_001177912.1	5	Standard
NM_001370489.1	RefSeq	NP_001357418.1	6	Standard

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

negative regulation of transcription by RNA polymerase II
ubiquinone biosynthetic process
determination of adult lifespan
response to drug
mitochondrial ATP synthesis coupled electron transport

Molecular Function

protein binding
2-octoprenyl-3-methyl-6-methoxy-1,4-benzoquinone hydroxylase 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
metal ion binding

Cellular Component

nucleus
mitochondrial inner membrane
extrinsic component of mitochondrial inner membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321998
Coding exons: 6
Length: 12497
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125746
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.463	153	138	1.11	0.00000839	1391
Missense (PolyPhen)		46	43.882	1.0483		429
Synonymous	-0.276	57	54.4	1.05	0.00000349	425
Loss of Function	0.418	9	10.5	0.861	5.12e-7	121

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00079	0.00079	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00021	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydroxylation of 2-polyprenyl-3-methyl-6- methoxy-1,4-benzoquinol (DMQH2) during ubiquinone biosynthesis. Has also a structural role in the COQ enzyme complex, stabilizing other COQ polypeptides. Involved in lifespan determination in a ubiquinone-independent manner. {ECO:0000255|HAMAP-Rule:MF_03194}.;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.728
RVIS EVS: -0.12
RVIS percentile EVS: 45.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.882

Gene Damage Prediction

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