COQ7

Summary

COQ7 (coenzyme Q7, hydroxylase, HGNC:2244) is a protein-coding gene on chromosome 16p12.3, encoding NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial (Q99807). 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. It is a selective cancer dependency (DepMap: 15.8% of cell lines).

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.

Source: NCBI Gene 10229 — RefSeq curated summary.

At a glance

• Gene–disease (curated): distal hereditary motor neuropathy (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 251 total — 8 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 15.8% of screened cell lines
• MANE Select transcript: NM_016138

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2244
Approved symbol	COQ7
Name	coenzyme Q7, hydroxylase
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	CLK-1, CAT5
Ensembl gene	ENSG00000167186
Ensembl biotype	protein_coding
OMIM	601683
Entrez	10229

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000321998, ENST00000544894, ENST00000561858, ENST00000564746, ENST00000566049, ENST00000566110, ENST00000567314, ENST00000568985, ENST00000569127, ENST00000569259, ENST00000569312, ENST00000907103, ENST00000937633

RefSeq mRNA: 9 — MANE Select: NM_016138 NM_001190983, NM_001370489, NM_001370490, NM_001370491, NM_001370492, NM_001370493, NM_001370494, NM_001370495, NM_016138

CCDS: CCDS10574, CCDS53993

Canonical transcript exons

ENST00000321998 — 6 exons

Exon	Start	End
ENSE00001110736	19073921	19074035
ENSE00001322596	19067614	19067737
ENSE00002575542	19078081	19080095
ENSE00003607253	19071928	19072106
ENSE00003626839	19075721	19075860
ENSE00003685863	19077306	19077374

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 90.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2566 / max 108.5483, expressed in 1807 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152981	5.7113	1744
152982	3.7675	1631
152980	2.1699	1238
152983	1.2287	731
152984	0.3792	144

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.90	gold quality
muscle of leg	UBERON:0001383	90.54	gold quality
gastrocnemius	UBERON:0001388	90.10	gold quality
calcaneal tendon	UBERON:0003701	89.59	gold quality
cortical plate	UBERON:0005343	88.31	gold quality
muscle organ	UBERON:0001630	88.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.54	gold quality
ventricular zone	UBERON:0003053	87.45	gold quality
right testis	UBERON:0004534	87.41	gold quality
left testis	UBERON:0004533	87.32	gold quality
testis	UBERON:0000473	87.12	gold quality
adrenal tissue	UBERON:0018303	87.08	gold quality
left ovary	UBERON:0002119	87.04	gold quality
heart left ventricle	UBERON:0002084	86.91	gold quality
colonic epithelium	UBERON:0000397	86.77	gold quality
apex of heart	UBERON:0002098	86.74	gold quality
cardiac ventricle	UBERON:0002082	86.55	gold quality
ganglionic eminence	UBERON:0004023	86.55	gold quality
triceps brachii	UBERON:0001509	86.51	silver quality
ovary	UBERON:0000992	86.08	gold quality
rectum	UBERON:0001052	85.94	gold quality
right atrium auricular region	UBERON:0006631	85.75	gold quality
right ovary	UBERON:0002118	85.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.13	gold quality
heart	UBERON:0000948	85.09	gold quality
mucosa of stomach	UBERON:0001199	84.93	gold quality
biceps brachii	UBERON:0001507	84.85	gold quality
tendon	UBERON:0000043	84.78	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: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
GLS2	Activation
NFE2L2	Repression
SOD2	Repression
WWOX	Repression

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

66 targeting COQ7, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-4666B	99.64	68.69	1282

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• action of clioquinol on several age-dependent neurodegenerative diseases with distinct etiologies might result from a slowing down of the aging process through action of the drug on CLK-1. (PMID:18927074)
• The siRNA-mediated knock down leads to an increase in cytoplasmic superoxide dismutase (SOD1) mRNA levels and activity (PMID:19135146)
• Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis. (PMID:25339443)
• Pathogenicity of two COQ7 mutations and responses to 2,4-dihydroxybenzoate bypass treatment. (PMID:28409910)
• Clinical spectrum in multiple families with primary COQ10 deficiency. (PMID:33215859)
• Association of ITPKB, IL1R2 and COQ7 with Parkinson’s disease in Taiwan. (PMID:34244037)
• Structure and functionality of a multimeric human COQ7:COQ9 complex. (PMID:36306796)
• A founder mutation in COQ7, p.(Leu111Pro), causes pure hereditary spastic paraplegia (HSP) in the Iranian population. (PMID:36854932)
• Biallelic variants in COQ7 cause distal hereditary motor neuropathy with upper motor neuron signs. (PMID:37170631)
• Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ10 deficiency: Hypomorphic variants and two distinct disease entities. (PMID:37392700)
• COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction. (PMID:38702428)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	coq7	ENSDARG00000062594
mus_musculus	Coq7	ENSMUSG00000030652
rattus_norvegicus	Coq7	ENSRNOG00000017012
drosophila_melanogaster	Coq7	FBGN0029502
caenorhabditis_elegans		WBGENE00000536

Protein

Protein identifiers

NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial — Q99807 (reviewed: Q99807)

Alternative names: 3-demethoxyubiquinone 3-hydroxylase (NADH), Timing protein clk-1 homolog, Ubiquinone biosynthesis monooxygenase COQ7

All UniProt accessions (6): Q99807, H3BP28, H3BS11, H3BSZ3, H3BTN8, I3L1T0

UniProt curated annotations — full annotation on UniProt →

Function. 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. Catalyzes the reaction through a substrate-mediated reduction pathway, whereby NADH shuttles electrons to 5-methoxy-2-methyl-3-(all-trans-decaprenyl)benzoquinone, which then transfers the electrons to the two Fe(3+) centers. The binding of 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone (DMQn) mediates reduction of the diiron center by nicotinamide adenine dinucleotide (NADH) and initiates oxygen activation for subsequent DMQ hydroxylation. The physiological substrates are 5-methoxy-2-methyl-3-(all-trans-nonaprenyl)benzoquinone (DMQ(9)) and 5-methoxy-2-methyl-3-(all-trans-decaprenyl)benzoquinone (DMQ(10)), however in vitro the enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency. Also has a structural role in the COQ enzyme complex, stabilizing other COQ polypeptides. Involved in lifespan determination in a ubiquinone-independent manner. Plays a role in modulating mitochondrial stress responses, acting in the nucleus, perhaps via regulating gene expression, independent of its characterized mitochondrial function in ubiquinone biosynthesis.

Subunit / interactions. Component of a multi-subunit COQ enzyme complex. Interacts with COQ8B and COQ6. Interacts with COQ9.

Subcellular location. Mitochondrion inner membrane. Mitochondrion. Nucleus. Chromosome.

Tissue specificity. Expressed dominantly in heart and skeletal muscle.

Disease relevance. Coenzyme Q10 deficiency, primary, 8 (COQ10D8) [MIM:616733] An autosomal recessive disorder resulting from mitochondrial dysfunction and characterized by decreased levels of coenzyme Q10. Patients manifest neonatal lung hypoplasia, contractures, early infantile hypertension and cardiac hypertrophy, secondary to prenatal kidney dysplasia, with neonatal and infantile renal dysfunction. Clinical features also include progressive peripheral neuropathy, muscular hypotonia and atrophy, and mild psychomotor delay with hearing and visual impairment. The disease is caused by variants affecting the gene represented in this entry. Neuronopathy, distal hereditary motor, autosomal recessive 9 (HMNR9) [MIM:620402] A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. HMNR9 is a slowly progressive form characterized by juvenile onset of distal muscle weakness and atrophy particularly affecting the lower limbs, although most patients also have upper limb involvement. Additional features include pes cavus, foot drop, and inability to walk on the heels or tiptoes. Some patients may have mild sensory abnormalities or pyramidal signs. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 iron ions per subunit.

Pathway. Cofactor biosynthesis; ubiquinone biosynthesis.

Similarity. Belongs to the COQ7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99807-1	1	yes
Q99807-2	2

RefSeq proteins (9): NP_001177912, NP_001357418, NP_001357419, NP_001357420, NP_001357421, NP_001357422, NP_001357423, NP_001357424, NP_057222* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009078	Ferritin-like_SF	Homologous_superfamily
IPR011566	Ubq_synth_Coq7	Family

Pfam: PF03232

Enzyme classification (BRENDA):

• EC 1.14.99.60 — 3-demethoxyubiquinol 3-hydroxylase (BRENDA: 7 organisms, 3 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• a 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone + NADH + O2 = a 3-demethylubiquinone + NAD(+) + H2O (RHEA:81211)

UniProt features (47 total): binding site 11, sequence variant 9, mutagenesis site 6, helix 6, sequence conflict 4, turn 4, repeat 2, region of interest 2, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7SSS	ELECTRON MICROSCOPY	2.4
7SSP	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99807-F1	87.17	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 93; 142; 178; 178; 181; 212; 216; 51; 60; 90; 90

Mutagenesis-validated functional residues (6):

Position	Phenotype
28	reduces nuclear localization. increases level of reactive oxygen species (ros).
51	loss of function activity; when associated with a-208; a-212 and a-216.
178	no detectable ubiquinone is produced.
208	loss of function activity; when associated with a-51; a-212 and a-216.
212	loss of function activity; when associated with a-51; a-208 and a-216.
216	loss of function activity; when associated with a-51; a-208 and a-212.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2142789	Ubiquinol biosynthesis

MSigDB gene sets: 252 (showing top): MORF_MSH3, YANG_BREAST_CANCER_ESR1_LASER_UP, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MORF_BRCA1, GOBP_KETONE_METABOLIC_PROCESS, MORF_RAD51L3, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_PRKCA, GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, NKX22_01, GOBP_KETONE_BIOSYNTHETIC_PROCESS, CREB_Q3, GOBP_DETERMINATION_OF_ADULT_LIFESPAN

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), ubiquinone biosynthetic process (GO:0006744), determination of adult lifespan (GO:0008340), regulation of gene expression (GO:0010468), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of reactive oxygen species metabolic process (GO:2000377)

GO Molecular Function (8): chromatin binding (GO:0003682), metal ion binding (GO:0046872), 3-demethoxyubiquinone 3-hydroxylase (NADH) activity (GO:0160224), monooxygenase activity (GO:0004497), protein binding (GO:0005515), 3-demethoxyubiquinol 3-hydroxylase activity (GO:0008682), oxidoreductase activity (GO:0016491), 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 (GO:0016709)

GO Cellular Component (7): nucleus (GO:0005634), chromosome (GO:0005694), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), extrinsic component of mitochondrial inner membrane (GO:0031314), ubiquinone biosynthesis complex (GO:0110142), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
binding	2
monooxygenase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
ubiquinone metabolic process	1
quinone biosynthetic process	1
multicellular organismal process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
positive regulation of DNA-templated transcription	1
regulation of metabolic process	1
reactive oxygen species metabolic process	1
cation binding	1
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	1
oxidoreductase activity	1
catalytic activity	1
intracellular membraneless organelle	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial inner membrane	1
extrinsic component of organelle membrane	1
catalytic complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COQ7	COQ9	O75208	977
COQ7	COQ5	Q5HYK3	974
COQ7	COQ6	Q9Y2Z9	963
COQ7	COQ4	Q9Y3A0	962
COQ7	COQ3	Q9NZJ6	961
COQ7	CLK3	P49761	893
COQ7	COQ8A	Q8NI60	887
COQ7	PDSS1	Q5T2R2	869
COQ7	COQ2	Q96H96	861
COQ7	COQ8B	Q96D53	861
COQ7	PDSS2	Q86YH6	843
COQ7	TELO2	Q9Y4R8	818
COQ7	IMMT	Q16891	814
COQ7	SLC7A4	O43246	723
COQ7	NDUFA9	Q16795	705

IntAct

40 interactions, top by confidence:

A	B	Type	Score
COQ8A	COQ9	psi-mi:“MI:0914”(association)	0.670
COQ3	COQ7	psi-mi:“MI:0407”(direct interaction)	0.590
COQ4	COQ7	psi-mi:“MI:0407”(direct interaction)	0.590
COQ5	COQ7	psi-mi:“MI:0407”(direct interaction)	0.590
COQ7	COQ3	psi-mi:“MI:0407”(direct interaction)	0.590
COQ7	COQ4	psi-mi:“MI:0407”(direct interaction)	0.590
COQ7	COQ5	psi-mi:“MI:0407”(direct interaction)	0.590
COQ7	COQ9	psi-mi:“MI:0407”(direct interaction)	0.590
COQ9	COQ7	psi-mi:“MI:0407”(direct interaction)	0.590
COQ9	COQ5	psi-mi:“MI:0915”(physical association)	0.590
COQ7	COQ9	psi-mi:“MI:0915”(physical association)	0.590
COQ5	COQ9	psi-mi:“MI:0914”(association)	0.590
COQ7	COQ6	psi-mi:“MI:0407”(direct interaction)	0.540
COQ6	COQ7	psi-mi:“MI:0407”(direct interaction)	0.540
COQ4	COQ5	psi-mi:“MI:0914”(association)	0.520
COQ3	COQ9	psi-mi:“MI:0914”(association)	0.500
COQ4	COQ9	psi-mi:“MI:0914”(association)	0.500
COQ7	AARS2	psi-mi:“MI:0915”(physical association)	0.400
Gpsm1	OARD1	psi-mi:“MI:0914”(association)	0.350
COQ5	ACOT7	psi-mi:“MI:0914”(association)	0.350
COQ7	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
PTPMT1	TIMM44	psi-mi:“MI:0914”(association)	0.350
COQ3	COQ8B	psi-mi:“MI:0914”(association)	0.350
COQ7	NRDC	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): COQ7 (Affinity Capture-MS), COQ7 (Reconstituted Complex), COQ7 (Reconstituted Complex), COQ7 (Affinity Capture-MS), BOLA3 (Affinity Capture-MS), COQ7 (Affinity Capture-MS), COQ7 (Affinity Capture-MS), COQ7 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), CHCHD2 (Affinity Capture-MS), COQ7 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), CYCS (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), PITRM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0M4FCN7, A2XSL4, B4G0F3, B8BKI7, C6JS30, D3ZLY0, F4JJJ3, M1BYJ7, O22832, O24428, O43272, O74826, P09925, P22243, P22337, P28492, P28645, P29108, P32061, P46253, P48376, P97478, Q01753, Q01771, Q04499, Q0P5A2, Q2R483, Q2TBW2, Q40731, Q41319, Q42770, Q42807, Q43593, Q4G064, Q56X52, Q571F8, Q5HYK3, Q5ZLL5, Q63619, Q66L51

Diamond homologs: O74826, P41735, P48376, P97478, Q2RNK3, Q2TBW2, Q54VB3, Q63619, Q99807, A1TKP1, A1W3V1, B9MDA8, A1VJY7, C1D7C0, Q12FJ1, Q8XVH7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COQ7	“form complex”	“CoQ biosynthetic complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ubiquinone biosynthetic process	7	364.1×	8e-16

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	110
Likely benign	88
Benign	21

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
219119	NM_016138.5(COQ7):c.422T>A (p.Val141Glu)	Pathogenic
2507386	NM_016138.5(COQ7):c.332T>C (p.Leu111Pro)	Pathogenic
2584639	NM_016138.5(COQ7):c.1A>G (p.Met1Val)	Pathogenic
2584640	NM_016138.5(COQ7):c.253-2A>T	Pathogenic
2584641	NM_016138.5(COQ7):c.467T>A (p.Leu156Gln)	Pathogenic
2584643	NM_016138.5(COQ7):c.467T>G (p.Leu156Arg)	Pathogenic
3062349	NM_016138.5(COQ7):c.334A>G (p.Met112Val)	Pathogenic
3062350	NM_016138.5(COQ7):c.613_617delinsCAT (p.Ala205fs)	Pathogenic
2573010	NM_016138.5(COQ7):c.1A>C (p.Met1Leu)	Likely pathogenic
2584462	NM_016138.5(COQ7):c.28_44dup (p.Arg16fs)	Likely pathogenic
929474	NM_016138.5(COQ7):c.599_600delinsTAATGCATC (p.Lys200fs)	Likely pathogenic

SpliceAI

955 predictions. Top by Δscore:

Variant	Effect	Δscore
16:19072104:CAGGT:C	donor_loss	1.0000
16:19072105:AGG:A	donor_loss	1.0000
16:19072106:GGTG:G	donor_loss	1.0000
16:19072108:T:G	donor_loss	1.0000
16:19073915:TTGCA:T	acceptor_loss	1.0000
16:19073916:TGCA:T	acceptor_loss	1.0000
16:19073917:GCA:G	acceptor_loss	1.0000
16:19073918:CA:C	acceptor_loss	1.0000
16:19073919:A:AG	acceptor_gain	1.0000
16:19073919:AG:A	acceptor_loss	1.0000
16:19073920:G:GG	acceptor_gain	1.0000
16:19073920:GAAA:G	acceptor_gain	1.0000
16:19075698:T:A	acceptor_gain	1.0000
16:19075703:T:A	acceptor_gain	1.0000
16:19075719:AG:A	acceptor_gain	1.0000
16:19075719:AGG:A	acceptor_gain	1.0000
16:19075720:GG:G	acceptor_gain	1.0000
16:19075720:GGG:G	acceptor_gain	1.0000
16:19077300:A:AG	acceptor_gain	1.0000
16:19077304:A:AG	acceptor_gain	1.0000
16:19077304:AGCT:A	acceptor_gain	1.0000
16:19077305:G:GG	acceptor_gain	1.0000
16:19077305:GCT:G	acceptor_gain	1.0000
16:19077305:GCTG:G	acceptor_gain	1.0000
16:19067782:C:G	donor_gain	0.9900
16:19071926:A:AG	acceptor_gain	0.9900
16:19071927:G:GG	acceptor_gain	0.9900
16:19071927:GCTT:G	acceptor_gain	0.9900
16:19072107:G:GG	donor_gain	0.9900
16:19073909:T:G	acceptor_gain	0.9900

AlphaMissense

1407 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:19073937:A:T	E90V	0.996
16:19077322:G:C	R175P	0.994
16:19073938:A:C	E90D	0.992
16:19073938:A:T	E90D	0.992
16:19072051:T:C	I66T	0.991
16:19073937:A:C	E90A	0.991
16:19075779:A:C	E142D	0.991
16:19075779:A:T	E142D	0.991
16:19074011:T:A	W115R	0.990
16:19074011:T:C	W115R	0.990
16:19075778:A:T	E142V	0.990
16:19072048:G:C	R65P	0.989
16:19073947:T:A	H93Q	0.988
16:19073947:T:G	H93Q	0.988
16:19074024:G:A	G119E	0.988
16:19075764:C:G	C137W	0.988
16:19074035:G:T	G123W	0.987
16:19075721:G:A	G123E	0.987
16:19075733:C:A	A127D	0.986
16:19075771:G:C	A140P	0.985
16:19074035:G:A	G123R	0.984
16:19074035:G:C	G123R	0.984
16:19072039:G:A	G62E	0.983
16:19072064:G:C	Q70H	0.983
16:19072064:G:T	Q70H	0.983
16:19075762:T:C	C137R	0.983
16:19072026:G:C	A58P	0.982
16:19072051:T:G	I66S	0.981
16:19073925:T:C	M86T	0.981
16:19072033:A:T	E60V	0.980

dbSNP variants (sampled 300 via entrez): RS1000039983 (16:19070470 C>A,T), RS1000277923 (16:19066539 A>C), RS1000420881 (16:19081192 G>C), RS1000452065 (16:19081638 T>TA), RS1000941876 (16:19077452 A>G), RS1001059878 (16:19075592 C>T), RS1001063858 (16:19071867 C>A,G,T), RS1001158061 (16:19081886 A>G), RS1001166973 (16:19075247 C>G,T), RS1001188327 (16:19078366 C>G,T), RS1001281624 (16:19072766 G>A), RS1001368417 (16:19077603 T>TTTTTC,TTTTTTTTTTTC,TTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTTG,TTTTTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTTTTTTTTTTTTC,TTTTTTTTTTTTTTTTTTTTTTTTTTTC), RS1001438205 (16:19075412 T>C), RS1001544080 (16:19067572 C>T), RS1001841257 (16:19068272 G>A)

Disease associations

OMIM: gene MIM:601683 | disease phenotypes: MIM:616733, MIM:620402

GenCC curated gene-disease

Disease	Classification	Inheritance
primary coenzyme Q10 deficiency 8	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
distal hereditary motor neuropathy	Strong	AR

Mondo (2): primary coenzyme Q10 deficiency 8 (MONDO:0014754), neuronopathy, distal hereditary motor, autosomal recessive 9 (MONDO:0957874)

Orphanet (1): COQ7-related distal hereditary motor neuropathy (Orphanet:658778)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000110	Renal dysplasia
HP:0000365	Hearing impairment
HP:0000505	Visual impairment
HP:0000726	Dementia
HP:0000822	Hypertension
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001271	Polyneuropathy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001562	Oligohydramnios
HP:0001712	Left ventricular hypertrophy
HP:0001761	Pes cavus
HP:0002089	Pulmonary hypoplasia
HP:0002098	Respiratory distress
HP:0002380	Fasciculations
HP:0003259	Elevated circulating creatinine concentration
HP:0003391	Gowers sign
HP:0003487	Babinski sign
HP:0003557	Increased variability in muscle fiber diameter
HP:0003577	Congenital onset
HP:0003621	Juvenile onset
HP:0005932	Abnormal renal corticomedullary differentiation

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004902_37	Parkinson’s disease	9.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630851 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
trichostatin A	decreases expression	2
aristolochic acid I	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Glyphosate	affects methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone	increases expression	1
Coumestrol	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4614067	Binding	Inhibition of COQ7 in human HeLa cells assessed as DMQ10 level per well at 10 uM after 2 days by HPLC analysis	Identification of small molecule inhibitors of human COQ7. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SJ61	HAP1 COQ7 (-) 1	Cancer cell line	Male
CVCL_SJ62	HAP1 COQ7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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