COQ2

Summary

COQ2 (coenzyme Q2, polyprenyltransferase, HGNC:25223) is a protein-coding gene on chromosome 4q21.23, encoding 4-hydroxybenzoate polyprenyltransferase, mitochondrial (Q96H96). Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis. It is a selective cancer dependency (DepMap: 39.0% of cell lines).

This gene encodes an enzyme that functions in the final steps in the biosynthesis of CoQ (ubiquinone), a redox carrier in the mitochondrial respiratory chain and a lipid-soluble antioxidant. This enzyme, which is part of the coenzyme Q10 pathway, catalyzes the prenylation of parahydroxybenzoate with an all-trans polyprenyl group. Mutations in this gene cause coenzyme Q10 deficiency, a mitochondrial encephalomyopathy, and also COQ2 nephropathy, an inherited form of mitochondriopathy with primary renal involvement.

Source: NCBI Gene 27235 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 447 total — 10 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 93
• Cancer dependency (DepMap): dependent in 39.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001358921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25223
Approved symbol	COQ2
Name	coenzyme Q2, polyprenyltransferase
Location	4q21.23
Locus type	gene with protein product
Status	Approved
Aliases	CL640, FLJ26072
Ensembl gene	ENSG00000173085
Ensembl biotype	protein_coding
OMIM	609825
Entrez	27235

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000311461, ENST00000311469, ENST00000503391, ENST00000503915, ENST00000514935, ENST00000647002

RefSeq mRNA: 2 — MANE Select: NM_001358921 NM_001358921, NM_015697

CCDS: CCDS47090, CCDS87234

Canonical transcript exons

ENST00000647002 — 7 exons

Exon	Start	End
ENSE00001181134	83269860	83269993
ENSE00001181138	83273496	83273617
ENSE00001181156	83272087	83272172
ENSE00003567969	83267586	83267774
ENSE00003600134	83263824	83264363
ENSE00003650769	83278948	83279114
ENSE00003816516	83284512	83284798

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 93.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2826 / max 179.8601, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52922	21.7610	1813
52923	0.5216	118

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.54	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.53	gold quality
gingival epithelium	UBERON:0001949	93.43	gold quality
biceps brachii	UBERON:0001507	93.39	gold quality
gingiva	UBERON:0001828	92.48	gold quality
vastus lateralis	UBERON:0001379	92.02	gold quality
monocyte	CL:0000576	91.83	gold quality
mononuclear cell	CL:0000842	91.71	gold quality
body of tongue	UBERON:0011876	91.35	gold quality
quadriceps femoris	UBERON:0001377	91.32	gold quality
leukocyte	CL:0000738	91.22	gold quality
skeletal muscle tissue	UBERON:0001134	90.83	gold quality
triceps brachii	UBERON:0001509	90.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.29	gold quality
gluteal muscle	UBERON:0002000	89.59	gold quality
muscle tissue	UBERON:0002385	88.90	gold quality
deltoid	UBERON:0001476	88.80	gold quality
muscle organ	UBERON:0001630	88.50	gold quality
skeletal muscle organ	UBERON:0014892	88.50	gold quality
palpebral conjunctiva	UBERON:0001812	88.48	gold quality
right adrenal gland	UBERON:0001233	88.42	gold quality
right adrenal gland cortex	UBERON:0035827	88.28	gold quality
left adrenal gland	UBERON:0001234	88.20	gold quality
heart right ventricle	UBERON:0002080	87.88	gold quality
adrenal cortex	UBERON:0001235	87.79	gold quality
left adrenal gland cortex	UBERON:0035825	87.70	gold quality
adrenal gland	UBERON:0002369	87.52	gold quality
diaphragm	UBERON:0001103	87.49	gold quality
endometrium epithelium	UBERON:0004811	87.40	gold quality
muscle of leg	UBERON:0001383	87.39	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

45 targeting COQ2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-4762-5P	99.57	68.54	1424

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 39.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 28)

• Treatment with CoQs having shorter isoprenoid chains, especially CoQ2, induced apoptosis in p53-point mutated BALL-1 cells, whereas treatment with longer isoprenoid chains did not. (PMID:15905035)
• Substitution of a highly conserved tyrosine to cysteine at amino acid 297 of COQ2 is the first molecular cause of primary CoQ(10) deficiency. (PMID:16400613)
• We have found that both 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate and sodium cholate, but not sodium deoxycholate, lysophosphatidyl choline, or octylglucoside, significantly stimulate ubiquinone activity over that measured with Triton X-100. (PMID:16643834)
• Our results support a requirement for CoQ(10) to control superoxide levels in HL-60 cells. (PMID:16873928)
• A deletirious frame shift deletion mutation that causes severe ubiquinone deficiency was identified in COQ2. (PMID:17332895)
• Study is the first direct demonstration of the pathogenicity of a COQ2 mutation involved in human disease, and establishes yeast as a useful model to study human CoQ(10) deficiency. (PMID:17374725)
• statin intolerance which is manifested primarily through muscle symptoms is associated with genomic variation in COQ2 (PMID:17376224)
• COQ2 mutations cause a primary glomerular disease with renal lesions that vary in severity and are not necessarily associated with neurological signs. (PMID:17855635)
• [review] Primary CoQ10 deficiency is due to defects in CoQ10 biosynthesis, while secondary forms are due to other causes. (PMID:22490322)
• A novel homozygous mutation in COQ2 (c.905C>T,p.Ala302Val) found in dizygotic twins is linked to fatal infantile multisystem disease. (PMID:23343605)
• Functionally impaired variants of COQ2 were associated with an increased risk of multiple-system atrophy in multiplex families and patients with sporadic disease. (PMID:23758206)
• The recessive COQ2 mutations recently were nominated to be the genetic cause in a subset of familial and sporadic MSA cases. (PMID:24262183)
• Multiple system atrophy due to recessive COQ2 mutations (including exon dosage) was not observed in our study (PMID:25373618)
• This study demonstrated that COQ2 gene variants associate with cerebellar subtype of multiple system atrophy in Chinese. (PMID:25594503)
• This case-control study shows no evidence for an association between ALS and the V393A variant of COQ2 in Han Chinese. (PMID:25613861)
• Results indicated that COQ2 tended to play a population-specific and subtype-depended role in conferring susceptibility to multiple system atrophy (PMID:26096180)
• The V393A variant in the COQ2 gene increases risk of PD. (PMID:26098829)
• Findings provide evidence that the previously reported association of COQ2 V393A polymorphism with increased risk of multiple system atrophy in Japanese also applies to Han Chinese, as well as more broadly to other East Asian populations (PMID:26590992)
• Recessive causative mutations in COQ2 are very rare in Italian multiple system atrophy patients. (PMID:27394078)
• We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient’s phenotype. (PMID:27493029)
• CoQ10 deficiency associated with steroid resistant nephrotic syndrome and novel COQ2 homozygous variant p.Gly390Ala was identified by Next Generation Sequencing in two cousins. (PMID:28044327)
• COQ2 variants contribute to the pathogenesis of Parkinson’s disease (PMID:29644397)
• identified homozygous or compound heterozygous mutations in COQ2 in multiplex families with multiple system atrophy (PMID:30613928)
• Results suggest that COQ2 is not a genetic risk factor for multiple system atrophy in Italian population. (PMID:31398377)
• Clinical spectrum in multiple families with primary COQ10 deficiency. (PMID:33215859)
• COQ2 mutation associated isolated nephropathy in two siblings from a Chinese pedigree. (PMID:33397173)
• COQ2 and SNCA polymorphisms interact with environmental factors to modulate the risk of multiple system atrophy and subtype disposition. (PMID:35748722)
• Identification of COQ2 as a regulator of proliferation and lipid peroxidation through genome-scale CRISPR-Cas9 screening in myeloma cells. (PMID:38462771)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	coq2	ENSDARG00000059510
mus_musculus	Coq2	ENSMUSG00000029319
rattus_norvegicus	Coq2	ENSRNOG00000002194
drosophila_melanogaster	Coq2	FBGN0037574
caenorhabditis_elegans		WBGENE00000762

Paralogs (1): COX10 (ENSG00000006695)

Protein

Protein identifiers

4-hydroxybenzoate polyprenyltransferase, mitochondrial — Q96H96 (reviewed: Q96H96)

Alternative names: 4-hydroxybenzoate decaprenyltransferase, COQ2 homolog, Para-hydroxybenzoate–polyprenyltransferase

All UniProt accessions (4): Q96H96, E2QRG7, E7EPM7, H0YAI0

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis. Catalyzes the prenylation of para-hydroxybenzoate (PHB) with an all-trans polyprenyl donor (such as all-trans-decaprenyl diphosphate). The length of the polyprenyl side chain varies depending on the species, in humans, the side chain is comprised of 10 isoprenyls (decaprenyl) producing CoQ10 (also known as ubiquinone), whereas rodents predominantly generate CoQ9. However, this specificity is not complete, human tissues have low amounts of CoQ9 and rodent organs contain some CoQ10. Plays a central role in the biosynthesis of CoQ10. CoQ10 is a vital molecule that transports electrons from mitochondrial respiratory chain complexes. CoQs also function as cofactors for uncoupling protein and play a role as regulators of the extracellularly-induced ceramide-dependent apoptotic pathway. Regulates mitochondrial permeability transition pore (mPTP) opening and ROS production (pivotal events in cell death) in a tissue specific manner.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Widely expressed. Present in all of the tissues tested. Expressed at higher level in skeletal muscle, adrenal glands and the heart.

Disease relevance. Coenzyme Q10 deficiency, primary, 1 (COQ10D1) [MIM:607426] An autosomal recessive disorder with variable manifestations consistent with 5 major phenotypes. The phenotypes include an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form. The disease is caused by variants affecting the gene represented in this entry. Multiple system atrophy 1 (MSA1) [MIM:146500] A progressive neurodegenerative disorder clinically characterized by parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Pathologically, it is characterized by degeneration of striatonigral and olivopontocerebellar structures, and glial cytoplasmic inclusions that consist of abnormally phosphorylated alpha-synuclein or tau. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; ubiquinone biosynthesis.

Miscellaneous. Potential minor and functional isoform produced by alternative initiation. Potential minor and functional isoform produced by alternative initiation. Potential minor and functional isoform produced by alternative initiation.

Similarity. Belongs to the UbiA prenyltransferase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96H96-1	1	yes
Q96H96-3	3
Q96H96-4	4
Q96H96-5	5
Q96H96-6	6

RefSeq proteins (2): NP_001345850, NP_056512 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000537	UbiA_prenyltransferase	Family
IPR006370	HB_polyprenyltransferase-like	Family
IPR030470	UbiA_prenylTrfase_CS	Conserved_site
IPR039653	Prenyltransferase	Family
IPR044878	UbiA_sf	Homologous_superfamily

Pfam: PF01040

Enzyme classification (BRENDA):

• EC 2.5.1.39 — 4-hydroxybenzoate polyprenyltransferase (BRENDA: 14 organisms, 40 substrates, 54 inhibitors, 9 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-HYDROXYBENZOATE	0.0011–0.054	3
NONAPRENYL DIPHOSPHATE	0.0008–0.14	2
FARNESYL DIPHOSPHATE	0.022	1
GERANYL DIPHOSPHATE	0.0597	1
GERANYLGERANYL DIPHOSPHATE	0.254	1
SOLANESYL DIPHOSPHATE	0.031	1

Catalyzed reactions (Rhea), 3 shown:

• all-trans-nonaprenyl diphosphate + 4-hydroxybenzoate = 4-hydroxy-3-(all-trans-nonaprenyl)benzoate + diphosphate (RHEA:17709)
• an all-trans-polyprenyl diphosphate + 4-hydroxybenzoate = a 4-hydroxy-3-(all-trans-polyprenyl)benzoate + diphosphate (RHEA:44504)
• all-trans-decaprenyl diphosphate + 4-hydroxybenzoate = 4-hydroxy-3-(all-trans-decaprenyl)benzoate + diphosphate (RHEA:44564)

UniProt features (49 total): sequence variant 23, topological domain 10, transmembrane region 9, splice variant 5, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96H96-F1	85.64	0.74

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-2142789	Ubiquinol biosynthesis

MSigDB gene sets: 329 (showing top): TGCGCANK_UNKNOWN, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_LIPID_METABOLIC_PROCESS, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_KETONE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_ISOPRENOID_BIOSYNTHETIC_PROCESS, GOBP_ISOPRENOID_METABOLIC_PROCESS, GOBP_QUINONE_METABOLIC_PROCESS

GO Biological Process (3): glycerol metabolic process (GO:0006071), ubiquinone biosynthetic process (GO:0006744), isoprenoid biosynthetic process (GO:0008299)

GO Molecular Function (4): prenyltransferase activity (GO:0004659), 4-hydroxybenzoate polyprenyltransferase activity (GO:0008412), transferase activity (GO:0016740), transferase activity, transferring alkyl or aryl (other than methyl) groups (GO:0016765)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), extrinsic component of mitochondrial inner membrane (GO:0031314), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	1
Metabolism of cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carbohydrate metabolic process	1
polyol metabolic process	1
ubiquinone metabolic process	1
quinone biosynthetic process	1
isoprenoid metabolic process	1
lipid biosynthetic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
prenyltransferase activity	1
catalytic activity	1
transferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial inner membrane	1
extrinsic component of organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2053 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COQ2	COQ9	O75208	984
COQ2	PDSS1	Q5T2R2	984
COQ2	COQ8A	Q8NI60	984
COQ2	PDSS2	Q86YH6	980
COQ2	COQ6	Q9Y2Z9	919
COQ2	COQ4	Q9Y3A0	913
COQ2	COQ8B	Q96D53	912
COQ2	SALL3	Q9BXA9	901
COQ2	APTX	Q7Z2E3	894
COQ2	COQ5	Q5HYK3	862
COQ2	COQ7	Q99807	861
COQ2	COQ3	Q9NZJ6	856
COQ2	UBIAD1	Q9Y5Z9	680
COQ2	ETFDH	Q16134	676
COQ2	COQ10B	Q9H8M1	672

IntAct

11 interactions, top by confidence:

A	B	Type	Score
COQ2	SLC25A5	psi-mi:“MI:0914”(association)	0.530
COQ2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
COQ2	RSL1D1	psi-mi:“MI:0914”(association)	0.350
COQ2	NME6	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): COQ2 (Affinity Capture-MS), WBSCR16 (Affinity Capture-MS), HOGA1 (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), NME6 (Affinity Capture-MS), NDUFV1 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), MRPS15 (Affinity Capture-MS), MRPL22 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), COX6C (Affinity Capture-MS), C1QBP (Affinity Capture-MS), NDUFAF2 (Affinity Capture-MS), AURKAIP1 (Affinity Capture-MS), ATP5E (Affinity Capture-MS)

ESM2 similar proteins: A1JHN0, A2XWN6, A8J0J0, K7WIZ6, O64886, O75027, P0C150, P21592, P32378, P55217, Q01IJ3, Q07560, Q0D576, Q0DAK7, Q0WUA3, Q10252, Q16QL3, Q1ACB3, Q298G6, Q2N2K1, Q2N2K2, Q2N2K3, Q2N2K4, Q499N4, Q4I5G1, Q4WP81, Q5BCK8, Q5N9A1, Q6BKW6, Q6C0L2, Q6CTW6, Q6FUG4, Q75F43, Q7S5E7, Q7X745, Q7XB13, Q7XB14, Q7XR51, Q7XUH5, Q8I7J4

Diamond homologs: A0A097ZPE3, A0A0B2XGM8, A0A0B5L778, A0A0U5CJV1, A0A1B7YCK2, A0A1Y0BRF7, A0A3G9GNJ4, A0A3T0ZHL4, A0A455LM21, A0A455LRX2, A0A455R413, A0A8D5M7V9, A0KSE2, A0Q4E4, A1RFH5, A1S2M4, A1T087, A3CZR1, A3N0I2, A3QIF2, A4IZX0, A4SZT5, A4Y0P0, A4YAV1, A5F4H4, A6VEG6, A6WT76, A7N0X0, A7N9N4, A8FQF8, A8GZR0, A9L4Q8, B0BPA2, B1ZMT0, B3H1F9, B5FCB4, B7V5P9, B8CTT5, B8E613, C1DK47

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

447 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	22
Uncertain significance	184
Likely benign	165
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031932	NM_001358921.2(COQ2):c.663G>A (p.Trp221Ter)	Pathogenic
1440	NM_001358921.2(COQ2):c.287G>A (p.Ser96Asn)	Pathogenic
1453830	NM_001358921.2(COQ2):c.284G>A (p.Trp95Ter)	Pathogenic
1921302	NM_001358921.2(COQ2):c.573del (p.Val192fs)	Pathogenic
1943129	NM_001358921.2(COQ2):c.1034dup (p.Leu345fs)	Pathogenic
2203551	NM_001358921.2(COQ2):c.551del (p.Leu184fs)	Pathogenic
3591270	NM_001358921.2(COQ2):c.73_99delinsAAGGA (p.Arg25fs)	Pathogenic
3769478	NM_015697.9(COQ2):c.40dup (p.Ala14fs)	Pathogenic
3906250	NM_001358921.2(COQ2):c.762+1del	Pathogenic
4694753	NM_001358921.2(COQ2):c.832_833del (p.Trp278fs)	Pathogenic
1324157	NM_001358921.2(COQ2):c.762+1G>T	Likely pathogenic
1339524	NM_001358921.2(COQ2):c.962T>A (p.Leu321Gln)	Likely pathogenic
1344670	NM_001358921.2(COQ2):c.26dup (p.Ala10fs)	Likely pathogenic
1436	NM_001358921.2(COQ2):c.740A>G (p.Tyr247Cys)	Likely pathogenic
1698355	NM_001358921.2(COQ2):c.71G>A (p.Trp24Ter)	Likely pathogenic
1942314	NM_001358921.2(COQ2):c.629-1G>A	Likely pathogenic
2022845	NM_001358921.2(COQ2):c.253+1G>A	Likely pathogenic
2439498	NM_001358921.2(COQ2):c.-27C>T	Likely pathogenic
2582412	NM_001358921.2(COQ2):c.508del (p.Ala170fs)	Likely pathogenic
2876040	NM_001358921.2(COQ2):c.543-2A>G	Likely pathogenic
2974827	NM_001358921.2(COQ2):c.629-3_629del	Likely pathogenic
3356057	NM_001358921.2(COQ2):c.505dup (p.Leu169fs)	Likely pathogenic
3380984	NM_001358921.2(COQ2):c.543-4_543del	Likely pathogenic
3591248	NM_001358921.2(COQ2):c.909C>A (p.Tyr303Ter)	Likely pathogenic
3591258	NM_001358921.2(COQ2):c.542+1G>A	Likely pathogenic
3591259	NM_001358921.2(COQ2):c.439C>T (p.Arg147Cys)	Likely pathogenic
375338	NM_001358921.2(COQ2):c.395T>G (p.Met132Arg)	Likely pathogenic
3899231	NM_001358921.2(COQ2):c.367C>T (p.Arg123Cys)	Likely pathogenic
3906249	NM_001358921.2(COQ2):c.199G>C (p.Ala67Pro)	Likely pathogenic
4281234	NM_001358921.2(COQ2):c.431C>T (p.Thr144Ile)	Likely pathogenic

SpliceAI

950 predictions. Top by Δscore:

Variant	Effect	Δscore
4:83267782:C:CT	acceptor_gain	1.0000
4:83279115:C:A	acceptor_loss	1.0000
4:83279116:T:C	acceptor_loss	1.0000
4:83267580:TCAAA:T	donor_loss	0.9900
4:83267581:CAAA:C	donor_loss	0.9900
4:83267582:AAAC:A	donor_loss	0.9900
4:83267583:AAC:A	donor_loss	0.9900
4:83267584:A:AG	donor_loss	0.9900
4:83267585:C:CT	donor_loss	0.9900
4:83267773:TC:T	acceptor_gain	0.9900
4:83267774:CCTAA:C	acceptor_gain	0.9900
4:83267775:C:CC	acceptor_gain	0.9900
4:83267776:T:A	acceptor_loss	0.9900
4:83267783:A:T	acceptor_gain	0.9900
4:83272168:CTATA:C	acceptor_gain	0.9900
4:83272169:TATA:T	acceptor_gain	0.9900
4:83272173:C:CC	acceptor_gain	0.9900
4:83273619:T:C	acceptor_gain	0.9900
4:83278943:ATTAC:A	donor_loss	0.9900
4:83278944:TTAC:T	donor_loss	0.9900
4:83278945:TA:T	donor_loss	0.9900
4:83278946:A:T	donor_loss	0.9900
4:83278947:CCTTT:C	donor_loss	0.9900
4:83279110:GGTTC:G	acceptor_gain	0.9900
4:83279112:TTC:T	acceptor_gain	0.9900
4:83279113:TC:T	acceptor_gain	0.9900
4:83279114:CC:C	acceptor_gain	0.9900
4:83279115:C:CC	acceptor_gain	0.9900
4:83279121:A:T	acceptor_gain	0.9900
4:83279125:A:AC	acceptor_gain	0.9900

AlphaMissense

2360 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:83269879:T:A	D248V	0.998
4:83264316:A:C	F333L	0.997
4:83264316:A:T	F333L	0.997
4:83264318:A:G	F333L	0.997
4:83269879:T:G	D248A	0.997
4:83269895:A:G	W243R	0.997
4:83269895:A:T	W243R	0.997
4:83272119:T:A	K199I	0.997
4:83279080:G:C	S96R	0.997
4:83279080:G:T	S96R	0.997
4:83279082:T:G	S96R	0.997
4:83279085:A:G	W95R	0.996
4:83279085:A:T	W95R	0.996
4:83269879:T:C	D248G	0.995
4:83272118:T:A	K199N	0.995
4:83272118:T:G	K199N	0.995
4:83269880:C:G	D248H	0.994
4:83269979:A:G	W215R	0.994
4:83269979:A:T	W215R	0.994
4:83269980:A:C	N214K	0.994
4:83269980:A:T	N214K	0.994
4:83272087:C:G	G210R	0.994
4:83278978:A:C	N130K	0.994
4:83278978:A:T	N130K	0.994
4:83269878:A:C	D248E	0.993
4:83269878:A:T	D248E	0.993
4:83269880:C:A	D248Y	0.993
4:83269993:C:T	G210D	0.993
4:83272172:A:C	S181R	0.993
4:83272172:A:T	S181R	0.993

dbSNP variants (sampled 300 via entrez): RS1000082943 (4:83268422 G>A), RS1000104416 (4:83285449 A>G), RS1000251734 (4:83268800 G>T), RS1000650600 (4:83263954 G>A), RS1000883263 (4:83270283 A>G), RS1000934750 (4:83263645 G>C), RS1001031052 (4:83274458 G>A), RS1001050346 (4:83277001 C>T), RS1001141337 (4:83267206 T>C,G), RS1001329864 (4:83275016 T>C), RS1001383700 (4:83275277 T>C), RS1001493298 (4:83268348 T>C), RS1001568607 (4:83282425 C>A,T), RS1001616725 (4:83268568 T>C), RS1001848617 (4:83280511 A>G)

Disease associations

OMIM: gene MIM:609825 | disease phenotypes: MIM:607426, MIM:146500

GenCC curated gene-disease

Disease	Classification	Inheritance
coenzyme Q10 deficiency, primary, 1	Definitive	Autosomal recessive
multiple system atrophy	Moderate	Autosomal recessive
Leigh syndrome with nephrotic syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (9): coenzyme Q10 deficiency, primary, 1 (MONDO:0011829), multiple system atrophy 1, susceptibility to (MONDO:0020715), multiple system atrophy (MONDO:0007803), mitochondrial disease (MONDO:0044970), nephrotic syndrome (MONDO:0005377), focal segmental glomerulosclerosis (MONDO:0100313), coenzyme Q10 deficiency (MONDO:0018151), kidney disorder (MONDO:0005240), (MONDO:0016816)

Orphanet (4): Leigh syndrome with nephrotic syndrome (Orphanet:255249), Multiple system atrophy (Orphanet:102), Mitochondrial disease (Orphanet:68380), Coenzyme Q10 deficiency (Orphanet:35656)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000572	Visual loss
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000802	Impotence
HP:0000815	Hypergonadotropic hypogonadism
HP:0000966	Hypohidrosis
HP:0000970	Anhidrosis
HP:0001089	Iris atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004033_5	QRS interval (sulfonylurea treatment interaction)	3.000000e-07
GCST010396_147	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007922	response to sulfonylurea
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D019578	Multiple System Atrophy	C10.177.575.550; C10.228.140.079.612; C10.228.662.550; C10.574.928.625
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C564403	Coenzyme Q10 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4693075	Toxicity	3	atorvastatin;HMG-CoA reductase inhibitors;rosuvastatin	Muscular Diseases
rs6535454	Toxicity	3	atorvastatin;HMG-CoA reductase inhibitors;rosuvastatin	Muscular Diseases

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4693075	COQ2	3	3.25	1	atorvastatin;HMG-CoA reductase inhibitors;rosuvastatin
rs6535454	COQ2	3	2.25	1	atorvastatin;HMG-CoA reductase inhibitors;rosuvastatin

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
cobaltous chloride	decreases expression	2
Resveratrol	affects cotreatment, increases expression	2
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	increases reaction, affects binding	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
phenethyl isothiocyanate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone	increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1

Cellosaurus cell lines

5 cell lines: 3 induced pluripotent stem cell, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E4U0	KOLF2.1J COQ2 20.9kbdel DEL/WT	Induced pluripotent stem cell	Male
CVCL_E7K7	KOLF2.1J COQ2 M128V SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7K8	KOLF2.1J COQ2 M128V SNV/WT	Induced pluripotent stem cell	Male
CVCL_SJ58	HAP1 COQ2 (-) 1	Cancer cell line	Male
CVCL_SJ59	HAP1 COQ2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00822913	PHASE4	UNKNOWN	Botulinum A Toxin in Patients With Parkinson’s Disease
NCT03924414	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Parkinson’s And Zoledronic Acid
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT00211224	PHASE3	TERMINATED	Neuroprotection and Natural History in Parkinson’s Plus Syndromes (NNIPPS)
NCT00738062	PHASE3	COMPLETED	Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)
NCT01287221	PHASE3	TERMINATED	Study of Rifampicin in Multiple System Atrophy
NCT02008721	PHASE3	COMPLETED	Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach
NCT03829657	PHASE3	TERMINATED	Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT03952806	PHASE3	COMPLETED	Study of BHV-3241 in Participants With Multiple System Atrophy
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT06706622	PHASE3	ACTIVE_NOT_RECRUITING	A Trial of Amlenetug (Lu AF82422) in Participants With Multiple System Atrophy (MSA)
NCT07446894	PHASE3	RECRUITING	MSA-01 in Multiple System Atrophy
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT00354731	PHASE3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	PHASE3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	PHASE3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	PHASE3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	PHASE3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	PHASE3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	PHASE3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	PHASE3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	PHASE3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	PHASE3	TERMINATED	Amiloride in Nephrotic Syndrome