primary coenzyme Q10 deficiency 8

Summary

primary coenzyme Q10 deficiency 8 (MONDO:0014754) is a disease caused by variants in COQ6 and COQ7, with 2 cohort genes.

At a glance

• Causal genes: COQ6 (GenCC Definitive), COQ7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary coenzyme Q10 deficiency 8
Mondo ID	MONDO:0014754
OMIM	616733
DOID	DOID:0070245
UMLS	C4225226
MedGen	908648
GARD	0025013
Is cancer (heuristic)	no

Also known as: coenzyme Q10 deficiency caused by mutation in COQ7 · coenzyme Q10 deficiency, primary, 8 · coenzyme Q10 deficiency, primary, type 8 · COQ10D8 · COQ7 coenzyme Q10 deficiency

Data availability: 19 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › coenzyme Q10 deficiency › primary coenzyme Q10 deficiency 8

Related subtypes (8): coenzyme Q10 deficiency, primary, 1, autosomal recessive ataxia due to ubiquinone deficiency, familial steroid-resistant nephrotic syndrome with sensorineural deafness, deafness-encephaloneuropathy-obesity-valvulopathy syndrome, coenzyme Q10 deficiency, primary, 3, encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome, neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome, coenzyme q10 deficiency, primary, 9

Subtypes (1): neuronopathy, distal hereditary motor, autosomal recessive 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 3 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685666	NM_016138.5(COQ7):c.635_636del (p.Tyr212fs)	COQ7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
219119	NM_016138.5(COQ7):c.422T>A (p.Val141Glu)	COQ7	Pathogenic	criteria provided, single submitter
2507386	NM_016138.5(COQ7):c.332T>C (p.Leu111Pro)	COQ7	Pathogenic	no assertion criteria provided
3062349	NM_016138.5(COQ7):c.334A>G (p.Met112Val)	COQ7	Pathogenic	no assertion criteria provided
3062350	NM_016138.5(COQ7):c.613_617delinsCAT (p.Ala205fs)	COQ7	Pathogenic	no assertion criteria provided
2573010	NM_016138.5(COQ7):c.1A>C (p.Met1Leu)	COQ7	Likely pathogenic	criteria provided, single submitter
2584462	NM_016138.5(COQ7):c.28_44dup (p.Arg16fs)	COQ7	Likely pathogenic	criteria provided, single submitter
929474	NM_016138.5(COQ7):c.599_600delinsTAATGCATC (p.Lys200fs)	COQ7	Likely pathogenic	criteria provided, single submitter
1463095	NM_016138.5(COQ7):c.3G>T (p.Met1Ile)	COQ7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
587428	NM_016138.5(COQ7):c.161G>A (p.Arg54Gln)	COQ7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
929475	NM_016138.5(COQ7):c.319C>T (p.Arg107Trp)	COQ7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1396906	NM_016138.5(COQ7):c.446A>G (p.Tyr149Cys)	COQ7	Uncertain significance	criteria provided, single submitter
1878532	NM_016138.5(COQ7):c.367+5G>A	COQ7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2580230	NM_016138.5(COQ7):c.160C>T (p.Arg54Trp)	COQ7	Uncertain significance	criteria provided, single submitter
2585135	NM_016138.5(COQ7):c.218T>A (p.Val73Asp)	COQ7	Uncertain significance	criteria provided, single submitter
587429	NM_016138.5(COQ7):c.9C>A (p.Cys3Ter)	COQ7	Uncertain significance	criteria provided, single submitter
678528	NM_016138.5(COQ7):c.308C>T (p.Thr103Met)	COQ7	Benign	criteria provided, multiple submitters, no conflicts
683572	NM_016138.5(COQ7):c.73+36T>G	COQ7	Benign	criteria provided, multiple submitters, no conflicts
683575	NM_016138.5(COQ7):c.74-29A>G	COQ7	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
COQ6	Definitive	Autosomal recessive	primary coenzyme Q10 deficiency 8	5
COQ7	Strong	Autosomal recessive	primary coenzyme Q10 deficiency 8	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COQ7	Orphanet:319678	Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome
COQ7	Orphanet:658778	COQ7-related distal hereditary motor neuropathy
COQ6	Orphanet:280406	Familial steroid-resistant nephrotic syndrome with sensorineural deafness
COQ6	Orphanet:93921	Full schwannomatosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COQ7	HGNC:2244	ENSG00000167186	Q99807	NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial	gencc,clinvar
COQ6	HGNC:20233	ENSG00000119723	Q9Y2Z9	Ubiquinone biosynthesis monooxygenase COQ6, mitochondrial	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ7	NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial	Catalyzes the hydroxylation of the 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone at the C6 position and participates in the biosynthesis of ubiquinone.
COQ6	Ubiquinone biosynthesis monooxygenase COQ6, mitochondrial	FAD-dependent monooxygenase required for two non-consecutive steps during ubiquinone biosynthesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COQ7	Enzyme (other)	yes	1.14.99.60	Ferritin-like_SF, Ubq_synth_Coq7
COQ6	Other/Unknown	no		UbQ_mOase_COQ6, FAD-bd, UbiH/COQ6

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
muscle of leg	1
primordial germ cell in gonad	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ7	236	ubiquitous	marker	primordial germ cell in gonad, hindlimb stylopod muscle, muscle of leg
COQ6	209	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COQ6	3,105
COQ7	1,137

Intra-cohort edges

A	B	Sources
COQ6	COQ7	intact, string_interaction

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COQ7	Q99807	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COQ6	Q9Y2Z9	84.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ubiquinol biosynthesis	2	878.5×	1e-06	COQ7, COQ6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ubiquinone biosynthetic process	2	936.2×	6e-06	COQ7, COQ6
regulation of reactive oxygen species metabolic process	1	366.4×	0.008	COQ7
determination of adult lifespan	1	216.1×	0.009	COQ7
regulation of gene expression	1	41.7×	0.036	COQ7
negative regulation of transcription by RNA polymerase II	1	8.9×	0.130	COQ7
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	COQ7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COQ7	0	0
COQ6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
COQ7	16	Binding:16

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
COQ7	1.14.99.60	3-demethoxyubiquinol 3-hydroxylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	COQ7
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COQ6

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COQ7	16	—
COQ6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.