coenzyme Q10 deficiency

Summary

coenzyme Q10 deficiency (MONDO:0018151) is a disease (an umbrella term covering 9 Mondo subtypes) caused by COQ8A (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: COQ8A (GenCC Definitive)
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 10
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coenzyme Q10 deficiency
Mondo ID	MONDO:0018151
MeSH	C564403
OMIM	607426
Orphanet	35656
DOID	DOID:0050730
ICD-11	1251664337
NCIT	C142083
SNOMED CT	724575009
UMLS	C1843920
MedGen	334528
GARD	0010423
Is cancer (heuristic)	no

Also known as: coenzyme Q10 deficiency disease · coenzyme Q10 deficiency, primary · CoQ10 deficiency · CoQ10 deficiency, primary

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record · 4 cell lines.

Disease family

An umbrella term covering 9 Mondo subtypes.

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

Related subtypes (47): mitochondrial respiratory chain complex deficiency, combined oxidative phosphorylation deficiency, myopathy, lactic acidosis, and sideroblastic anemia, optic atrophy 3, autosomal dominant optic atrophy, classic form, Leigh syndrome, mitochondrial non-syndromic sensorineural hearing loss, maternally-inherited diabetes and deafness, chronic diarrhea with villous atrophy, Kearns-Sayre syndrome, Leber hereditary optic neuropathy, NARP syndrome, deafness, aminoglycoside-induced, hereditary spastic paraplegia 7, spinocerebellar ataxia type 28, leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome, spastic ataxia 3, pontocerebellar hypoplasia type 6, autosomal recessive optic atrophy, OPA7 type, acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins, congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome, spastic ataxia 4, hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome, hereditary spastic paraplegia 55, cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, Charcot-Marie-Tooth disease recessive intermediate D, autosomal dominant mitochondrial myopathy with exercise intolerance, Charcot-Marie-Tooth disease type 4K, hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome, hereditary spastic paraplegia 77, fatal infantile encephalocardiomyopathy, FASTKD2-related infantile mitochondrial encephalomyopathy, autosomal dominant optic atrophy and peripheral neuropathy, ataxia neuropathy spectrum, maternally-inherited mitochondrial dystonia, Perrault syndrome, hypertrophic cardiomyopathy and renal tubular disease due to mitochondrial DNA mutation, adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy, mitochondrial DNA maintenance syndrome, mitochondrial DNA depletion syndrome, periodic paralysis with later-onset distal motor neuropathy, non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy, Zellweger-like syndrome without peroxisomal anomalies, maternally-inherited progressive external ophthalmoplegia, Leber plus disease, encephalopathy due to mitochondrial and peroxisomal fission defect, severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency

Subtypes (9): 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, primary coenzyme Q10 deficiency 8, coenzyme q10 deficiency, primary, 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

10 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic, 1 benign/likely benign, 1 not provided, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1438	NM_001358921.2(COQ2):c.440G>A (p.Arg147His)	COQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1440	NM_001358921.2(COQ2):c.287G>A (p.Ser96Asn)	COQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
375340	NM_001358921.2(COQ2):c.1047del (p.Asn351fs)	COQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1436	NM_001358921.2(COQ2):c.740A>G (p.Tyr247Cys)	COQ2	Likely pathogenic	criteria provided, single submitter
375338	NM_001358921.2(COQ2):c.395T>G (p.Met132Arg)	COQ2	Likely pathogenic	criteria provided, single submitter
60538	NM_001358921.2(COQ2):c.1009C>T (p.Arg337Ter)	COQ2	risk factor	no assertion criteria provided
1439	NM_001358921.2(COQ2):c.533A>G (p.Asn178Ser)	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
60536	NM_001358921.2(COQ2):c.232A>G (p.Met78Val)	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3645	NM_020247.5(COQ8A):c.993C>T (p.Phe331=)	COQ8A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
375339	NM_001358921.2(COQ2):c.755C>T (p.Ala252Val)	COQ2	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 3 · 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
COQ8A	Definitive	Autosomal recessive	coenzyme Q10 deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COQ8A	Orphanet:139485	Autosomal recessive ataxia due to ubiquinone deficiency
COQ2	Orphanet:227510	Multiple system atrophy, cerebellar type
COQ2	Orphanet:98933	Multiple system atrophy, parkinsonian type

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
COQ8A	HGNC:16812	ENSG00000163050	Q8NI60	Atypical kinase COQ8A, mitochondrial	gencc,clinvar
COQ2	HGNC:25223	ENSG00000173085	Q96H96	4-hydroxybenzoate polyprenyltransferase, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ8A	Atypical kinase COQ8A, mitochondrial	Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration.
COQ2	4-hydroxybenzoate polyprenyltransferase, mitochondrial	Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COQ8A	Kinase	yes		ABC1_dom, Kinase-like_dom_sf, ADCK3_dom
COQ2	Enzyme (other)	yes	2.5.1.39	UbiA_prenyltransferase, HB_polyprenyltransferase-like, UbiA_prenylTrfase_CS

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
gastrocnemius	1
hindlimb stylopod muscle	1
skeletal muscle tissue	1
gingival epithelium	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ8A	134	ubiquitous	marker	gastrocnemius, skeletal muscle tissue, hindlimb stylopod muscle
COQ2	284	ubiquitous	marker	skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COQ2	2,160
COQ8A	1,765

Intra-cohort edges

A	B	Sources
COQ2	COQ8A	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COQ8A	Q8NI60	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COQ2	Q96H96	85.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	2e-06	COQ8A, COQ2
Mitochondrial protein import	1	84.0×	0.012	COQ2

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×	4e-06	COQ8A, COQ2
isoprenoid biosynthetic process	1	842.6×	0.002	COQ2
phosphorylation	1	648.1×	0.002	COQ8A
glycerol metabolic process	1	561.7×	0.002	COQ2

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
COQ8A	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COQ8A	14	4
COQ2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	COQ8A
VANDETANIB	4	COQ8A
DASATINIB	4	COQ8A
ERLOTINIB	4	COQ8A
SARACATINIB	3	COQ8A
CANERTINIB	3	COQ8A
TG100-115	2	COQ8A
GALUNISERTIB	2	COQ8A
OSI-632	2	COQ8A
R-406	2	COQ8A
MILCICLIB	2	COQ8A
R-1487	1	COQ8A
CYC-116	1	COQ8A
AEW-541	1	COQ8A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
COQ8A	93	Binding:93

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
COQ2	2.5.1.39	4-hydroxybenzoate polyprenyltransferase

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

14 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	COQ8A
VANDETANIB	4	COQ8A
DASATINIB	4	COQ8A
ERLOTINIB	4	COQ8A
SARACATINIB	3	COQ8A
CANERTINIB	3	COQ8A
TG100-115	2	COQ8A
GALUNISERTIB	2	COQ8A
OSI-632	2	COQ8A
R-406	2	COQ8A
MILCICLIB	2	COQ8A
R-1487	1	COQ8A
CYC-116	1	COQ8A
AEW-541	1	COQ8A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	COQ8A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	COQ2
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COQ2	0	COQ8A

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders