coenzyme Q10 deficiency, primary, 1

Summary

coenzyme Q10 deficiency, primary, 1 (MONDO:0011829) is a disease caused by COQ2 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: COQ2 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 131

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coenzyme Q10 deficiency, primary, 1
Mondo ID	MONDO:0011829
OMIM	607426
DOID	DOID:0070238
UMLS	C3551954
MedGen	764868
GARD	0018378
Is cancer (heuristic)	no

Also known as: coenzyme Q10 deficiency caused by mutation in COQ2 · coenzyme Q10 deficiency, primary, 1 · coenzyme Q10 deficiency, primary, type 1 · COQ10D1 · COQ2 coenzyme Q10 deficiency

Data availability: 131 ClinVar variants · 2 GenCC gene-disease records.

Disease family

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 › coenzyme Q10 deficiency, primary, 1

Related subtypes (8): 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

131 retrieved; paginated sample, class counts are floors:

76 uncertain significance, 17 conflicting classifications of pathogenicity, 16 likely pathogenic, 7 likely benign, 5 pathogenic, 4 benign/likely benign, 3 benign, 3 pathogenic/likely pathogenic

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
2066540	NM_001358921.2(COQ2):c.967del (p.Ile323fs)	COQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3591270	NM_001358921.2(COQ2):c.73_99delinsAAGGA (p.Arg25fs)	COQ2	Pathogenic	criteria provided, single submitter
375340	NM_001358921.2(COQ2):c.1047del (p.Asn351fs)	COQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3769478	NM_015697.9(COQ2):c.40dup (p.Ala14fs)	COQ2	Pathogenic	criteria provided, single submitter
3906250	NM_001358921.2(COQ2):c.762+1del	COQ2	Pathogenic	criteria provided, single submitter
214229	NM_001358921.2(COQ2):c.132del (p.Gln44fs)	LOC112997540	Pathogenic	criteria provided, multiple submitters, no conflicts
1324157	NM_001358921.2(COQ2):c.762+1G>T	COQ2	Likely pathogenic	criteria provided, single submitter
1339524	NM_001358921.2(COQ2):c.962T>A (p.Leu321Gln)	COQ2	Likely pathogenic	criteria provided, single submitter
1436	NM_001358921.2(COQ2):c.740A>G (p.Tyr247Cys)	COQ2	Likely pathogenic	criteria provided, single submitter
1698355	NM_001358921.2(COQ2):c.71G>A (p.Trp24Ter)	COQ2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2439498	NM_001358921.2(COQ2):c.-27C>T	COQ2	Likely pathogenic	criteria provided, single submitter
3380984	NM_001358921.2(COQ2):c.543-4_543del	COQ2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3591248	NM_001358921.2(COQ2):c.909C>A (p.Tyr303Ter)	COQ2	Likely pathogenic	criteria provided, single submitter
3591258	NM_001358921.2(COQ2):c.542+1G>A	COQ2	Likely pathogenic	criteria provided, single submitter
3591259	NM_001358921.2(COQ2):c.439C>T (p.Arg147Cys)	COQ2	Likely pathogenic	criteria provided, single submitter
375338	NM_001358921.2(COQ2):c.395T>G (p.Met132Arg)	COQ2	Likely pathogenic	criteria provided, single submitter
3899231	NM_001358921.2(COQ2):c.367C>T (p.Arg123Cys)	COQ2	Likely pathogenic	criteria provided, single submitter
3906249	NM_001358921.2(COQ2):c.199G>C (p.Ala67Pro)	COQ2	Likely pathogenic	criteria provided, single submitter
590809	NM_020247.5(COQ8A):c.*72dup	COQ8A	Likely pathogenic	no assertion criteria provided
930030	NM_020247.5(COQ8A):c.280_284del (p.Ser95fs)	COQ8A	Likely pathogenic	criteria provided, single submitter
3591274	NM_001358921.2(COQ2):c.-16del	LOC112997540	Likely pathogenic	criteria provided, single submitter
807401	NM_001358921.2(COQ2):c.220T>A (p.Tyr74Asn)	LOC112997540	Likely pathogenic	criteria provided, single submitter
1341588	NM_001358921.2(COQ2):c.368G>A (p.Arg123His)	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1386267	NM_001358921.2(COQ2):c.830C>T (p.Pro277Leu)	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1419518	NM_001358921.2(COQ2):c.254-5C>G	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1439	NM_001358921.2(COQ2):c.533A>G (p.Asn178Ser)	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1718789	NM_001358921.2(COQ2):c.744T>A (p.Asp248Glu)	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
214220	NM_001358921.2(COQ2):c.-23C>G	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 5 · 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
COQ2	Definitive	Autosomal recessive	coenzyme Q10 deficiency, primary, 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COQ2	Orphanet:227510	Multiple system atrophy, cerebellar type
COQ2	Orphanet:98933	Multiple system atrophy, parkinsonian type
APTX	Orphanet:1168	Ataxia-oculomotor apraxia type 1
COQ8A	Orphanet:139485	Autosomal recessive ataxia due to ubiquinone deficiency
PPARGC1A	Orphanet:803	Amyotrophic lateral sclerosis

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COQ2	HGNC:25223	ENSG00000173085	Q96H96	4-hydroxybenzoate polyprenyltransferase, mitochondrial	gencc,clinvar
APTX	HGNC:15984	ENSG00000137074	Q7Z2E3	Aprataxin	clinvar
COQ8A	HGNC:16812	ENSG00000163050	Q8NI60	Atypical kinase COQ8A, mitochondrial	clinvar
PPARGC1A	HGNC:9237	ENSG00000109819	Q9UBK2	Peroxisome proliferator-activated receptor gamma coactivator 1-alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ2	4-hydroxybenzoate polyprenyltransferase, mitochondrial	Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis.
APTX	Aprataxin	DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair.
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.
PPARGC1A	Peroxisome proliferator-activated receptor gamma coactivator 1-alpha	Transcriptional coactivator for steroid receptors and nuclear receptors.

Protein-family classification

Druggable: 2 · Difficult: 1 · 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
Kinase	1	6.9×	0.538
Enzyme (other)	1	3.0×	0.538
Transcription factor	1	2.1×	0.538
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COQ2	Enzyme (other)	yes	2.5.1.39	UbiA_prenyltransferase, HB_polyprenyltransferase-like, UbiA_prenylTrfase_CS
APTX	Transcription factor	no	3.1.11.7	SMAD_FHA_dom_sf, HIT-like, Znf_C2H2_type
COQ8A	Kinase	yes		ABC1_dom, Kinase-like_dom_sf, ADCK3_dom
PPARGC1A	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, PGC-1

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	2
gingival epithelium	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
colonic epithelium	1
islet of Langerhans	1
primordial germ cell in gonad	1
gastrocnemius	1
skeletal muscle tissue	1
body of tongue	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ2	284	ubiquitous	marker	skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis, gingival epithelium
APTX	278	ubiquitous	marker	colonic epithelium, islet of Langerhans, primordial germ cell in gonad
COQ8A	134	ubiquitous	marker	gastrocnemius, skeletal muscle tissue, hindlimb stylopod muscle
PPARGC1A	252	broad	marker	renal medulla, body of tongue, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PPARGC1A	5,889
COQ2	2,160
APTX	2,077
COQ8A	1,765

Intra-cohort edges

A	B	Sources
APTX	COQ2	string_interaction
APTX	COQ8A	string_interaction
COQ2	COQ8A	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PPARGC1A	Q9UBK2	47
APTX	Q7Z2E3	11
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: 15. Enrichment computed across 4 evidence-associated genes (3 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 3 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	585.6×	5e-05	COQ2, COQ8A
Regulation of MITF-M dependent genes involved in metabolism	1	1268.9×	0.006	PPARGC1A
Activation of PPARGC1A (PGC-1alpha) by phosphorylation	1	380.7×	0.013	PPARGC1A
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	1	135.9×	0.020	PPARGC1A
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	126.9×	0.020	PPARGC1A
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	126.9×	0.020	PPARGC1A
Expression of BMAL (ARNTL), CLOCK, and NPAS2	1	97.6×	0.022	PPARGC1A
SUMOylation of transcription cofactors	1	81.0×	0.022	PPARGC1A
Heme signaling	1	71.8×	0.022	PPARGC1A
Transcriptional activation of mitochondrial biogenesis	1	68.0×	0.022	PPARGC1A
Regulation of RUNX2 expression and activity	1	60.4×	0.022	PPARGC1A
Mitochondrial protein import	1	56.0×	0.022	COQ2
Transcriptional regulation of white adipocyte differentiation	1	43.3×	0.026	PPARGC1A
PPARA activates gene expression	1	31.5×	0.034	PPARGC1A
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	27.6×	0.036	PPARGC1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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	468.1×	2e-04	COQ2, COQ8A
positive regulation of fatty acid oxidation	1	601.9×	0.017	PPARGC1A
isoprenoid biosynthetic process	1	421.3×	0.017	COQ2
single strand break repair	1	351.1×	0.017	APTX
phosphorylation	1	324.1×	0.017	COQ8A
response to dietary excess	1	280.9×	0.017	PPARGC1A
glycerol metabolic process	1	280.9×	0.017	COQ2
fatty acid oxidation	1	263.3×	0.017	PPARGC1A
respiratory electron transport chain	1	210.7×	0.017	PPARGC1A
positive regulation of gluconeogenesis	1	191.5×	0.017	PPARGC1A
temperature homeostasis	1	162.0×	0.017	PPARGC1A
digestion	1	156.0×	0.017	PPARGC1A
negative regulation of smooth muscle cell proliferation	1	156.0×	0.017	PPARGC1A
intracellular glucose homeostasis	1	145.3×	0.017	PPARGC1A
response to muscle activity	1	145.3×	0.017	PPARGC1A
response to starvation	1	117.0×	0.019	PPARGC1A
cellular respiration	1	108.0×	0.019	PPARGC1A
brown fat cell differentiation	1	108.0×	0.019	PPARGC1A
adipose tissue development	1	100.3×	0.020	PPARGC1A
transcription initiation at RNA polymerase II promoter	1	93.6×	0.020	PPARGC1A
gluconeogenesis	1	81.0×	0.022	PPARGC1A
energy homeostasis	1	68.0×	0.025	PPARGC1A
regulation of circadian rhythm	1	64.8×	0.025	PPARGC1A
circadian regulation of gene expression	1	58.5×	0.027	PPARGC1A
neuron apoptotic process	1	46.3×	0.033	PPARGC1A
positive regulation of cold-induced thermogenesis	1	40.9×	0.035	PPARGC1A
cellular response to oxidative stress	1	38.6×	0.035	PPARGC1A
mitochondrion organization	1	38.0×	0.035	PPARGC1A
regulation of protein stability	1	31.4×	0.041	APTX
protein-containing complex assembly	1	28.5×	0.044	PPARGC1A

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
APTX	0	0
PPARGC1A	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): 2.

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

Symbol	Assays	Type breakdown
COQ8A	93	Binding:93
PPARGC1A	12	Binding:12
APTX	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
COQ2	2.5.1.39	4-hydroxybenzoate polyprenyltransferase
APTX	3.1.11.7, 3.6.1.70, 3.6.1.71, 3.6.1.72	adenosine-5’-diphospho-5’-[DNA] diphosphatase, guanosine-5’-diphospho-5’-[DNA] diphosphatase, adenosine-5’-diphospho-5’-[DNA] diphosphatase, DNA-3’-diphospho-5’-guanosine diphosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	2	APTX, PPARGC1A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COQ2	0	COQ8A
APTX	1	—
PPARGC1A	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.