COQ9

Summary

COQ9 (coenzyme Q9, HGNC:25302) is a protein-coding gene on chromosome 16q21, encoding Ubiquinone biosynthesis protein COQ9, mitochondrial (O75208). Membrane-associated protein that warps the membrane surface to access and bind aromatic isoprenes with high specificity, including ubiquinone (CoQ) isoprene intermediates and presents them directly to COQ7, therefore facilitating the COQ7-mediated hydroxylase step.

This locus represents a mitochondrial ubiquinone biosynthesis gene. The encoded protein is likely necessary for biosynthesis of coenzyme Q10, as mutations at this locus have been associated with autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency.

Source: NCBI Gene 57017 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 358 total — 18 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 24
• MANE Select transcript: NM_020312

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25302
Approved symbol	COQ9
Name	coenzyme Q9
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434K046
Ensembl gene	ENSG00000088682
Ensembl biotype	protein_coding
OMIM	612837
Entrez	57017

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000262507, ENST00000562426, ENST00000562734, ENST00000563166, ENST00000563391, ENST00000564115, ENST00000564655, ENST00000565964, ENST00000566388, ENST00000567072, ENST00000567384, ENST00000567480, ENST00000567576, ENST00000567933, ENST00000568790, ENST00000569980, ENST00000895093, ENST00000895094, ENST00000895095, ENST00000895096, ENST00000934231, ENST00000960665, ENST00000960666, ENST00000960667, ENST00000960668

RefSeq mRNA: 1 — MANE Select: NM_020312 NM_020312

CCDS: CCDS32459

Canonical transcript exons

ENST00000262507 — 9 exons

Exon	Start	End
ENSE00000685246	57456931	57457015
ENSE00002616854	57447479	57447578
ENSE00002622774	57460589	57461270
ENSE00003461726	57459565	57459720
ENSE00003498489	57451040	57451208
ENSE00003554885	57456504	57456646
ENSE00003585045	57458246	57458350
ENSE00003590619	57460051	57460104
ENSE00003688302	57452801	57452936

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0359 / max 178.7524, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154377	23.0488	1813
154376	0.9871	613

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.42	gold quality
metanephros cortex	UBERON:0010533	97.77	gold quality
gastrocnemius	UBERON:0001388	97.68	gold quality
mucosa of transverse colon	UBERON:0004991	97.67	gold quality
right atrium auricular region	UBERON:0006631	97.58	gold quality
lower esophagus	UBERON:0013473	97.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.41	gold quality
muscle of leg	UBERON:0001383	97.20	gold quality
transverse colon	UBERON:0001157	97.18	gold quality
rectum	UBERON:0001052	97.14	gold quality
adrenal tissue	UBERON:0018303	97.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.07	gold quality
right adrenal gland cortex	UBERON:0035827	97.06	gold quality
right adrenal gland	UBERON:0001233	96.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.74	gold quality
right lobe of liver	UBERON:0001114	96.52	gold quality
lower esophagus mucosa	UBERON:0035834	96.50	gold quality
right lobe of thyroid gland	UBERON:0001119	96.45	gold quality
left adrenal gland	UBERON:0001234	96.39	gold quality
left adrenal gland cortex	UBERON:0035825	96.30	gold quality
left lobe of thyroid gland	UBERON:0001120	96.23	gold quality
body of stomach	UBERON:0001161	96.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.94	gold quality
right uterine tube	UBERON:0001302	95.67	gold quality
heart left ventricle	UBERON:0002084	95.63	gold quality
left testis	UBERON:0004533	95.63	gold quality
cerebellar hemisphere	UBERON:0002245	95.56	gold quality
cardiac atrium	UBERON:0002081	95.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

35 targeting COQ9, 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-4795-3P	100.00	74.62	4024
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1266-5P	97.71	66.92	1052

Literature-anchored findings (GeneRIF, showing 5)

• There is a homozygous stop mutation affecting a highly conserved residue of COQ9, leading to the truncation of 75 amino acids. (PMID:19375058)
• Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis. (PMID:25339443)
• family with CoQ10 deficiency caused by mutations in the COQ9 gene (PMID:29560582)
• DDIT3 Directs a Dual Mechanism to Balance Glycolysis and Oxidative Phosphorylation during Glutamine Deprivation. (PMID:34105294)
• Structure and functionality of a multimeric human COQ7:COQ9 complex. (PMID:36306796)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	coq9	ENSDARG00000023583
mus_musculus	Coq9	ENSMUSG00000031782
rattus_norvegicus	Coq9	ENSRNOG00000016190
drosophila_melanogaster	Coq9	FBGN0050493

Protein

Protein identifiers

Ubiquinone biosynthesis protein COQ9, mitochondrial — O75208 (reviewed: O75208)

All UniProt accessions (8): O75208, H3BNT2, H3BPC6, H3BPW3, H3BPY0, H3BRC0, H3BSJ5, H3BVA5

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-associated protein that warps the membrane surface to access and bind aromatic isoprenes with high specificity, including ubiquinone (CoQ) isoprene intermediates and presents them directly to COQ7, therefore facilitating the COQ7-mediated hydroxylase step. Participates in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration.

Subunit / interactions. Homodimer. Heterodimer; two heterodimers of COQ7:COQ9 come together on the same side of the lipid pseudo-bilayer and form a curved tetramer with a hydrophobic surface suitable for membrane interaction. These two tetramers assemble into a soluble octamer with a pseudo-bilayer of lipids captured within. Interacts with COQ7; this interaction allows ubiquinone (CoQ) isoprene intermediates presentation to COQ7 and facilitates the COQ7-mediated hydroxylase step.

Subcellular location. Mitochondrion.

Post-translational modifications. In response to mitochondrial stress, the precursor protein is ubiquitinated by the SIFI complex in the cytoplasm before mitochondrial import, leading to its degradation. Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1.

Disease relevance. Coenzyme Q10 deficiency, primary, 5 (COQ10D5) [MIM:614654] A form of coenzyme Q10 deficiency, 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.

Domain organisation. Structurally similar to the bacterial FadR protein (fatty acid metabolism regulator protein).

Pathway. Cofactor biosynthesis; ubiquinone biosynthesis.

Similarity. Belongs to the COQ9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75208-1	1	yes
O75208-2	2

RefSeq proteins (1): NP_064708* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012762	Ubiq_biosynth_COQ9	Family
IPR013718	COQ9_C	Domain
IPR048674	COQ9_HTH	Domain

Pfam: PF08511, PF21392

UniProt features (44 total): mutagenesis site 19, helix 14, compositionally biased region 2, splice variant 2, transit peptide 1, chain 1, region of interest 1, short sequence motif 1, strand 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6AWL	X-RAY DIFFRACTION	2
6DEW	X-RAY DIFFRACTION	2
4RHP	X-RAY DIFFRACTION	2.39
7SSS	ELECTRON MICROSCOPY	2.4
7SSP	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75208-F1	78.16	0.57

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 (1): 244

Post-translational modifications (1): 175

Mutagenesis-validated functional residues (19):

Position	Phenotype
190	impairs interaction with coq7.
227	impairs interaction with coq7.
237	impairs interaction with coq7.
240	abolishes interaction with coq7.
240	disrupts the octameric coq7:coq9 complex.
241	abolishes interaction with coq7.
256	impairs interaction with coq7.
288	decreases membrane association; when associated with a-291.
290	significantly decreases membrane association; when associated with a-297; a-298; a-301 and a-302.
290	decreases membrane association by more than 60%; when associated with a-297; a-298; a-301 and a-302.
291	decreases membrane association; when associated with a-288.
297	significantly decreases membrane association; when associated with a-290; a-298; a-301 and a-302.
297	decreases membrane association by more than 60%; when associated with a-290; a-298; a-301 and a-302.
298	significantly decreases membrane association; when associated with a-290; a-297; a-301 and a-302.
298	decreases membrane association by more than 60%; when associated with a-290; a-297; a-301 and a-302.
301	significantly decreases membrane association; when associated with a-290; a-297; a-298 and a-302.
301	decreases membrane association by more than 60%; when associated with a-290; a-297; a-298 and a-302.
302	significantly decreases membrane association; when associated with a-290; a-297; a-298 and a-301.
302	decreases membrane association by more than 60%; when associated with a-290; a-297; a-298 and a-301.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2142789	Ubiquinol biosynthesis

MSigDB gene sets: 219 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MORF_HDAC2, GOBP_KETONE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_OXIDATIVE_PHOSPHORYLATION, MODULE_301, GOBP_ELECTRON_TRANSPORT_CHAIN, MORF_PRKDC, GOCC_MITOCHONDRIAL_ENVELOPE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_KETONE_BIOSYNTHETIC_PROCESS, chr16q21, MORF_AATF

GO Biological Process (2): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), ubiquinone biosynthetic process (GO:0006744)

GO Molecular Function (5): enzyme activator activity (GO:0008047), lipid binding (GO:0008289), isoprenoid binding (GO:0019840), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), ubiquinone biosynthesis complex (GO:0110142)

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
binding	2
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
ubiquinone metabolic process	1
quinone biosynthetic process	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
lipid binding	1
identical protein binding	1
protein dimerization activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
catalytic complex	1

Protein interactions and networks

STRING

1612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COQ9	PDSS1	Q5T2R2	985
COQ9	COQ8A	Q8NI60	985
COQ9	COQ3	Q9NZJ6	984
COQ9	COQ2	Q96H96	984
COQ9	COQ7	Q99807	977
COQ9	COQ5	Q5HYK3	976
COQ9	PDSS2	Q86YH6	968
COQ9	COQ6	Q9Y2Z9	957
COQ9	COQ4	Q9Y3A0	949
COQ9	COQ8B	Q96D53	903
COQ9	APTX	Q7Z2E3	828
COQ9	NDUFA9	Q16795	738
COQ9	ETFDH	Q16134	699
COQ9	COQ10A	Q96MF6	674
COQ9	COQ10B	Q9H8M1	673

IntAct

149 interactions, top by confidence:

A	B	Type	Score
COQ8A	COQ9	psi-mi:“MI:0914”(association)	0.670
COQ9	ACSF2	psi-mi:“MI:0915”(physical association)	0.670
COQ9	COQ8A	psi-mi:“MI:0915”(physical association)	0.670
LYRM7	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
COQ5	COQ9	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: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
COQ9	PLSCR2	psi-mi:“MI:0915”(physical association)	0.560
COQ9	EHHADH	psi-mi:“MI:0915”(physical association)	0.560
COQ9	BMP10	psi-mi:“MI:0915”(physical association)	0.560
COQ9	CCL4L1	psi-mi:“MI:0915”(physical association)	0.560
COQ9	ALDH18A1	psi-mi:“MI:0915”(physical association)	0.560
COQ9	CTXN3	psi-mi:“MI:0915”(physical association)	0.560
COQ9	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
COQ9	ORMDL1	psi-mi:“MI:0915”(physical association)	0.560
COQ9	PPGB	psi-mi:“MI:0915”(physical association)	0.560
MGLL	COQ9	psi-mi:“MI:0915”(physical association)	0.560
COQ9	CYBC1	psi-mi:“MI:0915”(physical association)	0.560
CYB561D2	COQ9	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	COQ9	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (231): COQ9 (Affinity Capture-RNA), COQ9 (Two-hybrid), COQ9 (Reconstituted Complex), COQ7 (Reconstituted Complex), COQ3 (Reconstituted Complex), COQ4 (Reconstituted Complex), COQ5 (Reconstituted Complex), COQ6 (Reconstituted Complex), L2HGDH (Affinity Capture-MS), SPG20 (Affinity Capture-MS), DHRS7B (Affinity Capture-MS), SYNJ2BP (Affinity Capture-MS), RTN4IP1 (Affinity Capture-MS), RAB32 (Affinity Capture-MS), SDR39U1 (Affinity Capture-MS)

ESM2 similar proteins: A5GZW8, A6H773, A6QPI4, D3ZAW2, O14521, O75208, P09925, Q05B67, Q08BI9, Q12887, Q15070, Q15526, Q2KHV4, Q2NL34, Q3B8P0, Q3SYV3, Q3TD49, Q4KLZ1, Q5EA03, Q5G2C6, Q5PQL3, Q5R460, Q5R5H4, Q5R7D0, Q5RC29, Q5RE99, Q5T6X4, Q5XIJ4, Q5XJY4, Q5ZIS0, Q5ZLJ4, Q68FN7, Q68FT1, Q6AZR3, Q6AZV0, Q6DGM2, Q6P355, Q6PCT8, Q800L1, Q8BSF4

Diamond homologs: O13850, O75208, Q2NL34, Q3B8B2, Q5PPX7, Q5RJV0, Q68FT1, Q75CR6, Q8K1Z0, Q8MKN0, Q86HS0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COQ9	“form complex”	“CoQ biosynthetic complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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	6	90.6×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	5
Uncertain significance	151
Likely benign	137
Benign	17

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1027680	NM_020312.4(COQ9):c.73G>A (p.Val25Met)	Pathogenic
1360076	NM_020312.4(COQ9):c.592G>T (p.Glu198Ter)	Pathogenic
1402898	NM_020312.4(COQ9):c.521+1G>A	Pathogenic
1451347	NM_020312.4(COQ9):c.196C>T (p.Gln66Ter)	Pathogenic
192296	NM_020312.4(COQ9):c.521+1del	Pathogenic
1924901	NM_020312.4(COQ9):c.197_198del (p.Gln66fs)	Pathogenic
1931230	NM_020312.4(COQ9):c.679_680del (p.Met227fs)	Pathogenic
1937704	NM_020312.4(COQ9):c.202dup (p.Ala68fs)	Pathogenic
2021204	NM_020312.4(COQ9):c.679dup (p.Met227fs)	Pathogenic
2029732	NM_020312.4(COQ9):c.85C>T (p.Arg29Ter)	Pathogenic
2637678	NM_020312.4(COQ9):c.157C>T (p.Gln53Ter)	Pathogenic
2910403	NM_020312.4(COQ9):c.711+3G>C	Pathogenic
3076335	NM_020312.4(COQ9):c.521+2T>C	Pathogenic
3382518	NM_020312.4(COQ9):c.262G>T (p.Glu88Ter)	Pathogenic
3656843	NM_020312.4(COQ9):c.170C>G (p.Ser57Ter)	Pathogenic
3700330	NM_020312.4(COQ9):c.409_412del (p.Met137fs)	Pathogenic
431	NM_020312.4(COQ9):c.730C>T (p.Arg244Ter)	Pathogenic
4780104	NM_020312.4(COQ9):c.714dup (p.Asn239Ter)	Pathogenic
1324161	NM_020312.4(COQ9):c.74-2A>G	Likely pathogenic
1324162	NM_020312.4(COQ9):c.522-1G>A	Likely pathogenic
3723095	NM_020312.4(COQ9):c.711+2T>G	Likely pathogenic
3769405	NM_020312.4(COQ9):c.242+2T>G	Likely pathogenic
4413300	NM_020312.4(COQ9):c.522-2A>G	Likely pathogenic

SpliceAI

1354 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57451038:A:AG	acceptor_gain	1.0000
16:57451038:AGT:A	acceptor_gain	1.0000
16:57451039:G:GA	acceptor_gain	1.0000
16:57451039:GTG:G	acceptor_gain	1.0000
16:57451206:CAG:C	donor_loss	1.0000
16:57451207:AGGT:A	donor_loss	1.0000
16:57451208:GGT:G	donor_loss	1.0000
16:57451209:G:C	donor_loss	1.0000
16:57451210:T:A	donor_loss	1.0000
16:57458348:GAT:G	donor_gain	1.0000
16:57458351:G:GG	donor_gain	1.0000
16:57459563:A:AG	acceptor_gain	1.0000
16:57459564:G:GG	acceptor_gain	1.0000
16:57459564:GT:G	acceptor_gain	1.0000
16:57459564:GTTT:G	acceptor_gain	1.0000
16:57459564:GTTTA:G	acceptor_gain	1.0000
16:57459716:AGCAG:A	donor_gain	1.0000
16:57459717:GCAG:G	donor_gain	1.0000
16:57459717:GCAGG:G	donor_gain	1.0000
16:57459718:CAGG:C	donor_loss	1.0000
16:57459721:G:GG	donor_gain	1.0000
16:57451033:GTTTC:G	acceptor_loss	0.9900
16:57451034:TTTCA:T	acceptor_loss	0.9900
16:57451035:TTCA:T	acceptor_loss	0.9900
16:57451037:CAGTG:C	acceptor_loss	0.9900
16:57451038:A:G	acceptor_loss	0.9900
16:57451038:AGTG:A	acceptor_gain	0.9900
16:57451039:GT:G	acceptor_gain	0.9900
16:57451039:GTGG:G	acceptor_gain	0.9900
16:57451039:GTGGC:G	acceptor_gain	0.9900

AlphaMissense

2074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57452904:T:A	W116R	0.998
16:57452904:T:C	W116R	0.998
16:57452906:G:C	W116C	0.995
16:57452906:G:T	W116C	0.995
16:57456978:T:C	L190P	0.994
16:57452877:G:C	A107P	0.993
16:57456975:G:C	R189T	0.993
16:57452878:C:A	A107D	0.992
16:57452905:G:C	W116S	0.992
16:57456975:G:T	R189I	0.992
16:57459634:G:C	D261H	0.991
16:57456976:A:C	R189S	0.990
16:57456976:A:T	R189S	0.990
16:57459667:T:C	F272L	0.990
16:57459669:C:A	F272L	0.990
16:57459669:C:G	F272L	0.990
16:57459680:G:C	R276P	0.990
16:57452928:G:A	G124R	0.989
16:57452928:G:C	G124R	0.989
16:57452932:C:A	A125D	0.987
16:57459671:T:C	L273P	0.987
16:57452916:G:C	A120P	0.986
16:57456562:T:A	I146K	0.986
16:57458247:C:A	A203D	0.986
16:57452931:G:C	A125P	0.984
16:57457007:T:A	W200R	0.984
16:57457007:T:C	W200R	0.984
16:57456595:T:C	L157P	0.983
16:57452890:T:A	V111E	0.982
16:57452929:G:A	G124E	0.982

dbSNP variants (sampled 300 via entrez): RS1000544294 (16:57450394 G>A), RS1000578466 (16:57450734 T>C), RS1001171937 (16:57452825 G>A,C), RS1002150901 (16:57458666 G>A), RS1002174450 (16:57451572 G>A,T), RS1002432579 (16:57446022 T>G), RS1002497114 (16:57458421 G>A), RS1002767174 (16:57445847 T>G), RS1002815766 (16:57461708 C>T), RS1002840599 (16:57454323 G>C), RS1002871928 (16:57454722 G>A,T), RS1003197466 (16:57461442 A>G), RS1003877657 (16:57445511 A>G), RS1004224976 (16:57460329 A>T), RS1004523664 (16:57455730 G>T)

Disease associations

OMIM: gene MIM:612837 | disease phenotypes: MIM:614654, MIM:256000

GenCC curated gene-disease

Disease	Classification	Inheritance
encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR
Leigh syndrome	Limited	AR

Mondo (2): encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome (MONDO:0013840), Leigh syndrome (MONDO:0009723)

Orphanet (2): Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome (Orphanet:319678), Leigh syndrome (Orphanet:506)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001511	Intrauterine growth retardation
HP:0001612	Weak cry
HP:0001662	Bradycardia
HP:0001712	Left ventricular hypertrophy
HP:0002045	Hypothermia
HP:0002059	Cerebral atrophy
HP:0002093	Respiratory insufficiency
HP:0002151	Increased circulating lactate concentration
HP:0003128	Lactic acidosis
HP:0003348	Hyperalaninemia
HP:0003623	Neonatal onset
HP:0005484	Secondary microcephaly
HP:0011968	Feeding difficulties
HP:0034369	Decreased level of coenzyme Q10 in skeletal muscle

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
Doxorubicin	affects expression, increases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Irinotecan	decreases expression	1
Leflunomide	decreases expression	1
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone	increases expression	1
Folic Acid	decreases expression	1
Hydrogen Peroxide	increases expression	1
Ivermectin	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2V0	Abcam HEK293T COQ9 KO	Transformed cell line	Female
CVCL_SJ63	HAP1 COQ9 (-) 1	Cancer cell line	Male
CVCL_SJ64	HAP1 COQ9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01721733	PHASE2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	PHASE2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	PHASE2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	PHASE2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	PHASE2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01780168	Not specified	RECRUITING	The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT03137355	Not specified	RECRUITING	The International Registry for Leigh Syndrome
NCT05277363	Not specified	WITHDRAWN	A Study of the Natural Course of SURF1 Deficiency
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06967831	Not specified	RECRUITING	Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells