mitochondrial myopathy with reversible cytochrome C oxidase deficiency

Summary

mitochondrial myopathy with reversible cytochrome C oxidase deficiency (MONDO:0010780) is a disease with 10 cohort genes. The dominant Reactome pathway is Mitochondrial translation termination (8 cohort genes).

At a glance

• Cohort genes: 10
• ClinVar variants: 17
• Phenotypes (HPO): 24

Clinical features

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0001290	Generalized hypotonia	Very frequent (80-99%)
HP:0001324	Muscle weakness	Very frequent (80-99%)
HP:0003198	Myopathy	Very frequent (80-99%)
HP:0003200	Ragged-red muscle fibers	Very frequent (80-99%)
HP:0003688	Cytochrome C oxidase-negative muscle fibers	Very frequent (80-99%)
HP:0009051	Increased muscle glycogen content	Very frequent (80-99%)
HP:0009058	Increased muscle lipid content	Very frequent (80-99%)
HP:0001265	Hyporeflexia	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)
HP:0004900	Severe lactic acidosis	Frequent (30-79%)
HP:0008180	Mildly elevated creatine kinase	Frequent (30-79%)
HP:0011923	Decreased activity of mitochondrial complex I	Frequent (30-79%)
HP:0000158	Macroglossia	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000707	Abnormality of the nervous system	Occasional (5-29%)
HP:0001392	Abnormality of the liver	Occasional (5-29%)
HP:0001626	Abnormality of the cardiovascular system	Occasional (5-29%)
HP:0002033	Poor suck	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0003234	Decreased circulating carnitine concentration	Occasional (5-29%)
HP:0004887	Respiratory failure requiring assisted ventilation	Occasional (5-29%)
HP:0005946	Ventilator dependence with inability to wean	Occasional (5-29%)
HP:0011470	Nasogastric tube feeding in infancy	Occasional (5-29%)
HP:0002194	Delayed gross motor development	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial myopathy with reversible cytochrome C oxidase deficiency
Mondo ID	MONDO:0010780
OMIM	500009
Orphanet	254864
ICD-11	723205095
UMLS	C3151898
MedGen	463248
GARD	0017227
Is cancer (heuristic)	no

Also known as: benign COX deficiency · infantile reversible cytochrome C oxidase deficiency myopathy · mitochondrial myopathy with reversible complex IV deficiency · mitochondrial myopathy with reversible COX deficiency · mitochondrial myopathy, infantile, transient · MMIT · reversible infantile cytochrome C oxidase deficiency · reversible infantile respiratory chain deficiency

Data availability: 17 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › congenital structural myopathy › inborn mitochondrial myopathy › mitochondrial myopathy with reversible cytochrome C oxidase deficiency

Related subtypes (23): myopathy, lactic acidosis, and sideroblastic anemia, mitochondrial encephalomyopathy, progressive external ophthalmoplegia, mitochondrial myopathy with a defect in mitochondrial-protein transport, Barth syndrome, mitochondrial myopathy with diabetes, lethal infantile mitochondrial myopathy, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, mitochondrial trifunctional protein deficiency, adenosine monophosphate deaminase deficiency, congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome, autosomal dominant mitochondrial myopathy with exercise intolerance, fatal infantile encephalocardiomyopathy, mitochondrial myopathy-lactic acidosis-deafness syndrome, mitochondrial neurogastrointestinal encephalomyopathy, adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy, maternally-inherited progressive external ophthalmoplegia, mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy, mitochondrial complex II deficiency, nuclear type, mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome, X-linked recessive mitochondrial myopathy, mitochondrial complex I deficiency, nuclear type 1, COX deficiency, benign infantile mitochondrial myopathy

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

17 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1710006	NC_012920.1(MT-CO2):m.8156del	MT-CO2	Likely pathogenic	criteria provided, single submitter
9681	NC_012920.1(MT-CYB):m.15150G>A	MT-CYB	Likely pathogenic	reviewed by expert panel
692374	NC_012920.1(MT-ND1):m.3571del	MT-ND1	Likely pathogenic	reviewed by expert panel
693440	NC_012920.1(MT-ND5):m.12425del	MT-ND5	Likely pathogenic	reviewed by expert panel
9618	NC_012920.1(MT-TE):m.14674T>C	MT-TE	Likely pathogenic	reviewed by expert panel
692961	NC_012920.1(MT-ATP6):m.8719G>A	MT-ATP6	Uncertain significance	reviewed by expert panel
692624	NC_012920.1(MT-CO1):m.6145G>A	MT-CO1	Uncertain significance	reviewed by expert panel
692717	NC_012920.1(MT-CO1):m.7222A>G	MT-CO1	Uncertain significance	reviewed by expert panel
9657	NC_012920.1(MT-CO3):m.9379G>A	MT-CO3	Uncertain significance	reviewed by expert panel
9678	NC_012920.1(MT-CYB):m.15615G>A	MT-CYB	Uncertain significance	reviewed by expert panel
9679	NC_012920.1(MT-CYB):m.14846G>A	MT-CYB	Uncertain significance	reviewed by expert panel
9683	NC_012920.1(MT-CYB):m.15579A>G	MT-CYB	Uncertain significance	reviewed by expert panel
692361	NC_012920.1(MT-ND1):m.3502T>C	MT-ND1	Uncertain significance	reviewed by expert panel
692585	NC_012920.1(MT-ND2):m.5367_5385del	MT-ND2	Uncertain significance	reviewed by expert panel
693492	NC_012920.1(MT-ND5):m.12858C>A	MT-ND5	Uncertain significance	criteria provided, single submitter
30003	NC_012920.1(MT-TE):m.14674T>G	MT-TE	Uncertain significance	reviewed by expert panel
618220	NC_012920.1(MT-TE):m.14701C>T	MT-TE	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 37 · 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
TRMU	Supportive	Mitochondrial	mitochondrial myopathy with reversible cytochrome C oxidase deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRMU	Orphanet:217371	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
TRMU	Orphanet:254864	Mitochondrial myopathy with reversible cytochrome C oxidase deficiency
TRMU	Orphanet:90641	Rare mitochondrial non-syndromic sensorineural deafness
MT-ATP6	Orphanet:104	Leber hereditary optic neuropathy
MT-ATP6	Orphanet:225154	Familial infantile bilateral striatal necrosis
MT-ATP6	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP6	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ATP6	Orphanet:320360	MT-ATP6-related mitochondrial spastic paraplegia
MT-ATP6	Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy
MT-ATP6	Orphanet:644	NARP syndrome
MT-CO1	Orphanet:104	Leber hereditary optic neuropathy
MT-CO1	Orphanet:254905	Isolated cytochrome C oxidase deficiency
MT-CO1	Orphanet:550	MELAS
MT-CO1	Orphanet:90641	Rare mitochondrial non-syndromic sensorineural deafness
MT-CO1	Orphanet:99845	Genetic recurrent myoglobinuria
MT-CO2	Orphanet:254905	Isolated cytochrome C oxidase deficiency
MT-CO2	Orphanet:550	MELAS
MT-CO3	Orphanet:104	Leber hereditary optic neuropathy
MT-CO3	Orphanet:254905	Isolated cytochrome C oxidase deficiency
MT-CO3	Orphanet:550	MELAS
MT-CO3	Orphanet:99845	Genetic recurrent myoglobinuria
MT-CYB	Orphanet:104	Leber hereditary optic neuropathy
MT-CYB	Orphanet:137675	Histiocytoid cardiomyopathy
MT-CYB	Orphanet:1460	Isolated complex III deficiency
MT-ND1	Orphanet:104	Leber hereditary optic neuropathy
MT-ND1	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ND1	Orphanet:2609	Isolated complex I deficiency
MT-ND1	Orphanet:550	MELAS
MT-ND2	Orphanet:104	Leber hereditary optic neuropathy
MT-ND2	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ND2	Orphanet:2609	Isolated complex I deficiency
MT-ND5	Orphanet:104	Leber hereditary optic neuropathy
MT-ND5	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ND5	Orphanet:550	MELAS
MT-ND5	Orphanet:551	MERRF
MT-TE	Orphanet:254864	Mitochondrial myopathy with reversible cytochrome C oxidase deficiency
MT-TE	Orphanet:2596	Myopathy and diabetes mellitus

Cohort genes → proteins

10 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRMU	HGNC:25481	ENSG00000100416	O75648	Mitochondrial tRNA-specific 2-thiouridylase 1	gencc
MT-ATP6	HGNC:7414	ENSG00000198899	P00846	ATP synthase F(0) complex subunit a	clinvar
MT-CO1	HGNC:7419	ENSG00000198804	P00395	Cytochrome c oxidase subunit 1	clinvar
MT-CO2	HGNC:7421	ENSG00000198712	P00403	Cytochrome c oxidase subunit 2	clinvar
MT-CO3	HGNC:7422	ENSG00000198938	P00414	Cytochrome c oxidase subunit 3	clinvar
MT-CYB	HGNC:7427	ENSG00000198727	P00156	Cytochrome b	clinvar
MT-ND1	HGNC:7455	ENSG00000198888	P03886	NADH-ubiquinone oxidoreductase chain 1	clinvar
MT-ND2	HGNC:7456	ENSG00000198763	P03891	NADH-ubiquinone oxidoreductase chain 2	clinvar
MT-ND5	HGNC:7461	ENSG00000198786	P03915	NADH-ubiquinone oxidoreductase chain 5	clinvar
MT-TE	HGNC:7479	ENSG00000210194		mitochondrially encoded tRNA-Glu (GAA/G)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRMU	Mitochondrial tRNA-specific 2-thiouridylase 1	Catalyzes the 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln).
MT-ATP6	ATP synthase F(0) complex subunit a	Subunit a, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of th…
MT-CO1	Cytochrome c oxidase subunit 1	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
MT-CO2	Cytochrome c oxidase subunit 2	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
MT-CO3	Cytochrome c oxidase subunit 3	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
MT-CYB	Cytochrome b	Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain.
MT-ND1	NADH-ubiquinone oxidoreductase chain 1	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.
MT-ND2	NADH-ubiquinone oxidoreductase chain 2	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.
MT-ND5	NADH-ubiquinone oxidoreductase chain 5	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 8 · Druggable fraction: 0.2

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
Enzyme (other)	2	2.4×	0.200
Other/Unknown	8	1.4×	0.200

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRMU	Enzyme (other)	yes	2.1.1.61	MnmA-like, Rossmann-like_a/b/a_fold, MnmA-like_central_sf
MT-ATP6	Other/Unknown	no		ATP_synth_F0_asu, ATP_synth_F0_asu_AS, F0_ATP_A_sf
MT-CO1	Enzyme (other)	yes	7.1.1.9	Cyt_C_Oxase_1, Cyt_c_Oxase_su1_BS, Cyt_c_oxase-like_su1_dom
MT-CO2	Other/Unknown	no		Copper_CuA, CcO_II-like_C, Cupredoxin
MT-CO3	Other/Unknown	no		Cyt_c_oxidase-like_su3, Cyt_c_oxidase_su3_a-hlx, Cyt_c/ubiquinol_Oxase_su3
MT-CYB	Other/Unknown	no		Cyt_b/b6_N, Cyt_b/b6_C, Di-haem_cyt_TM
MT-ND1	Other/Unknown	no		NADH_UbQ_OxRdtase_su1/FPO, NADH_UbQ_OxRdtase_su1_CS
MT-ND2	Other/Unknown	no		ND/Mrp_TM, NADH_UbQ_OxRdtase_chain2, NADH_DH_su2_C
MT-ND5	Other/Unknown	no		Proton_antipo_N, ND/Mrp_TM, NU5C-like
MT-TE	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

10 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	3
rectum	3
left uterine tube	2
granulocyte	2
zone of skin	2
adipose tissue	2
metanephros cortex	1
right hemisphere of cerebellum	1
descending thoracic aorta	1
mucosa of stomach	1
stromal cell of endometrium	1
transverse colon	1
endocervix	1
pituitary gland	1
frontal cortex	1
gastrocnemius	1
right uterine tube	1
heart right ventricle	1
lateral nuclear group of thalamus	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRMU	259	ubiquitous	marker	apex of heart, right hemisphere of cerebellum, metanephros cortex
MT-ATP6	134	ubiquitous	marker	mucosa of stomach, left uterine tube, descending thoracic aorta
MT-CO1	134	ubiquitous	marker	granulocyte, stromal cell of endometrium, rectum
MT-CO2	134	ubiquitous	marker	granulocyte, rectum, transverse colon
MT-CO3	134	ubiquitous	marker	zone of skin, endocervix, rectum
MT-CYB	134	ubiquitous	marker	apex of heart, pituitary gland, zone of skin
MT-ND1	134	ubiquitous	marker	adipose tissue, gastrocnemius, frontal cortex
MT-ND2	134	broad	marker	adipose tissue, right uterine tube, left uterine tube
MT-ND5	247	ubiquitous	marker	heart right ventricle, postcentral gyrus, lateral nuclear group of thalamus
MT-TE	118	broad	marker	skeletal muscle tissue, sural nerve, apex of heart

Protein interactions among cohort

Intra-cohort edges: 27.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-CO1	3,547
MT-ND1	3,537
MT-CYB	3,317
MT-CO2	3,057
MT-ATP6	2,869
MT-ND5	2,825
MT-ND2	2,658
MT-CO3	1,791
TRMU	1,739
MT-TE	0

Intra-cohort edges

A	B	Sources
MT-ATP6	MT-CO1	string_interaction
MT-ATP6	MT-CO2	string_interaction
MT-ATP6	MT-CO3	string_interaction
MT-ATP6	MT-CYB	string_interaction
MT-ATP6	MT-ND1	string_interaction
MT-ATP6	MT-ND2	string_interaction
MT-ATP6	MT-ND5	string_interaction
MT-CO1	MT-CO2	string_interaction
MT-CO1	MT-CO3	string_interaction
MT-CO1	MT-CYB	string_interaction
MT-CO1	MT-ND1	string_interaction
MT-CO1	MT-ND2	string_interaction
MT-CO1	MT-ND5	string_interaction
MT-CO2	MT-CO3	intact, string_interaction
MT-CO2	MT-CYB	string_interaction
MT-CO2	MT-ND2	string_interaction
MT-CO2	MT-ND5	string_interaction
MT-CO3	MT-CYB	string_interaction
MT-CO3	MT-ND1	string_interaction
MT-CO3	MT-ND2	string_interaction
MT-CO3	MT-ND5	string_interaction
MT-CYB	MT-ND1	string_interaction
MT-CYB	MT-ND2	string_interaction
MT-CYB	MT-ND5	string_interaction
MT-ND1	MT-ND2	string_interaction
MT-ND1	MT-ND5	string_interaction
MT-ND2	MT-ND5	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-ATP6	P00846	10
MT-ND2	P03891	7
MT-ND5	P03915	7
MT-CYB	P00156	5
MT-ND1	P03886	5
MT-CO2	P00403	4
MT-CO1	P00395	3
MT-CO3	P00414	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRMU	O75648	89.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 10 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial translation termination	8	97.6×	6e-15	MT-ATP6, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND5
Respiratory electron transport	7	74.0×	4e-12	MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND5
Mitochondrial protein degradation	6	76.1×	2e-10	MT-ATP6, MT-CO1, MT-CO2, MT-ND1, MT-ND2, MT-ND5
Complex IV assembly	3	76.1×	3e-05	MT-CO1, MT-CO2, MT-CO3
Cytoprotection by HMOX1	3	61.4×	5e-05	MT-CO1, MT-CO2, MT-CO3
Complex I biogenesis	3	55.2×	5e-05	MT-ND1, MT-ND2, MT-ND5
TP53 Regulates Metabolic Genes	3	43.3×	9e-05	MT-CO1, MT-CO2, MT-CO3
tRNA modification in the mitochondrion	1	115.3×	0.019	TRMU
Formation of ATP by chemiosmotic coupling	1	63.4×	0.031	MT-ATP6
Complex III assembly	1	48.8×	0.037	MT-CYB
tRNA processing	1	39.6×	0.039	TRMU
Cristae formation	1	38.5×	0.039	MT-ATP6
Mitochondrial biogenesis	1	18.7×	0.072	MT-ATP6
Aerobic respiration and respiratory electron transport	1	9.8×	0.125	MT-ATP6
Organelle biogenesis and maintenance	1	7.3×	0.154	MT-ATP6
Metabolism of RNA	1	4.6×	0.221	TRMU
Metabolism of proteins	1	1.4×	0.555	MT-ATP6
Metabolism	1	1.3×	0.555	MT-ATP6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to hypoxia	6	63.8×	3e-09	MT-CO1, MT-CO2, MT-CYB, MT-ND1, MT-ND2, MT-ND5
cellular respiration	4	192.1×	5e-08	MT-CO1, MT-CO2, MT-CO3, MT-CYB
proton motive force-driven mitochondrial ATP synthesis	4	117.0×	3e-07	MT-ATP6, MT-ND1, MT-ND2, MT-ND5
aerobic respiration	4	110.1×	3e-07	MT-CO1, MT-ND1, MT-ND2, MT-ND5
mitochondrial electron transport, cytochrome c to oxygen	3	255.3×	1e-06	MT-CO1, MT-CO2, MT-CO3
mitochondrial respiratory chain complex I assembly	3	137.0×	6e-06	MT-ND1, MT-ND2, MT-ND5
electron transport coupled proton transport	2	936.2×	7e-06	MT-CYB, MT-ND5
mitochondrial electron transport, NADH to ubiquinone	3	119.5×	7e-06	MT-ND1, MT-ND2, MT-ND5
response to copper ion	2	340.4×	5e-05	MT-CO1, MT-CYB
response to hyperoxia	2	249.7×	9e-05	MT-ATP6, MT-CYB
ATP synthesis coupled electron transport	1	1872.4×	0.002	MT-CO2
response to D-galactosamine	1	1872.4×	0.002	MT-CYB
response to cobalamin	1	936.2×	0.003	MT-CYB
response to ethanol	2	32.6×	0.004	MT-CO2, MT-CYB
tRNA wobble position uridine thiolation	1	468.1×	0.005	TRMU
respiratory chain complex IV assembly	1	267.5×	0.007	MT-CO3
response to mercury ion	1	267.5×	0.007	MT-CYB
response to hydroperoxide	1	187.2×	0.010	MT-ND1
response to glucagon	1	187.2×	0.010	MT-CYB
mitochondrial electron transport, ubiquinol to cytochrome c	1	144.0×	0.011	MT-CYB
response to xenobiotic stimulus	2	15.3×	0.011	MT-CYB, MT-ND1
respiratory electron transport chain	1	93.6×	0.016	MT-CO1
proton motive force-driven ATP synthesis	1	89.2×	0.017	MT-ATP6
response to cadmium ion	1	81.4×	0.017	MT-CYB
response to electrical stimulus	1	72.0×	0.019	MT-CO1
animal organ regeneration	1	66.9×	0.019	MT-CYB
response to hydrogen peroxide	1	52.0×	0.023	MT-ND5
reactive oxygen species metabolic process	1	52.0×	0.023	MT-ND2
lactation	1	46.8×	0.025	MT-CO2
cerebellum development	1	39.8×	0.028	MT-CO1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 9

Druggability breadth: 7 of 10 evidence-associated genes (70%) 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
MT-CO2	CELECOXIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MT-CO2	6	4
TRMU	0	0
MT-ATP6	0	0
MT-CO1	0	0
MT-CO3	0	0
MT-CYB	0	0
MT-ND1	0	0
MT-ND2	0	0
MT-ND5	0	0
MT-TE	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CELECOXIB	4	MT-CO2
ROFECOXIB	4	MT-CO2
DICLOFENAC	4	MT-CO2
INDOMETHACIN	4	MT-CO2
VALDECOXIB	4	MT-CO2
TOLFENAMIC ACID	2	MT-CO2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
MT-CO2	47	Binding:41, ADMET:5, Toxicity:1
MT-CO1	19	Binding:12, Functional:4, ADMET:2, Toxicity:1
MT-ND1	5	Binding:5
MT-ND2	4	Binding:4
MT-ND5	4	Binding:4
MT-ATP6	1	Binding:1
MT-CO3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TRMU	2.1.1.61	tRNA 5-(aminomethyl)-2-thiouridylate-methyltransferase
MT-CO1	7.1.1.9	cytochrome-c oxidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

6 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)
CELECOXIB	4	MT-CO2
ROFECOXIB	4	MT-CO2
DICLOFENAC	4	MT-CO2
INDOMETHACIN	4	MT-CO2
VALDECOXIB	4	MT-CO2
TOLFENAMIC ACID	2	MT-CO2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MT-CO2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MT-CO1
D	Druggable family + AlphaFold only, no drug	1	TRMU
E	Difficult family or no structure, no drug	7	MT-ATP6, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND5, MT-TE

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MT-CO1	19	MT-CO2
MT-CO3	1	MT-CO2
TRMU	0	—
MT-ATP6	1	—
MT-CYB	0	—
MT-ND1	5	—
MT-ND2	4	—
MT-ND5	4	—
MT-TE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.