Inborn mitochondrial myopathy

disease

On this page

Also known as mitochondrial myopathy

Summary

Inborn mitochondrial myopathy (MONDO:0009637) is a disease (an umbrella term covering 24 Mondo subtypes) caused by FDX2 (GenCC Strong), with 13 cohort genes and 40 clinical trials. Top therapeutic interventions include omaveloxolone, elamipretide, and nicotinamide riboside.

At a glance

Causal gene: FDX2 (GenCC Strong)
Umbrella term: 24 Mondo subtypes
Cohort genes: 13
ClinVar variants: 27
Clinical trials: 40

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inborn mitochondrial myopathy
Mondo ID	MONDO:0009637
MeSH	D017240
Orphanet	206966
DOID	DOID:699
ICD-11	601991549
NCIT	C101328
UMLS	C0162670
MedGen	56484
GARD	0020371
MedDRA	10027710
Is cancer (heuristic)	no

Also known as: mitochondrial myopathy

Data availability: 27 ClinVar variants · 1 GenCC gene-disease record · 2 cell lines.

Disease family

An umbrella term covering 24 Mondo subtypes.

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

Related subtypes (5): autosomal dominant centronuclear myopathy, congenital fiber-type disproportion myopathy, myofibrillar myopathy, nemaline myopathy, autosomal dominant nebulin-related 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

27 retrieved; paginated sample, class counts are floors:

6 benign/likely benign, 6 uncertain significance, 4 conflicting classifications of pathogenicity, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 2 not provided, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
977147	NM_018116.4(MSTO1):c.706G>C (p.Asp236His)	MSTO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18249	NM_001151.4(SLC25A4):c.368C>A (p.Ala123Asp)	SLC25A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
219191	NM_178526.5(SLC25A42):c.871A>G (p.Asn291Asp)	SLC25A42	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
623644	NM_001397406.1(FDX2):c.422C>T (p.Pro141Leu)	FDX2	Likely pathogenic	criteria provided, single submitter
691525	NM_015340.4(LARS2):c.308G>A (p.Arg103His)	LARS2	Likely pathogenic	criteria provided, single submitter
9617	NC_012920.1(MT-TE):m.14709T>C	MT-TE	Likely pathogenic	reviewed by expert panel
9556	NC_012920.1(MT-TW):m.5521G>A	MT-TW	Likely pathogenic	reviewed by expert panel
143059	NM_001397406.1(FDX2):c.1A>T (p.Met1Leu)	FDX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
226694	NM_015340.4(LARS2):c.1552G>A (p.Asp518Asn)	LARS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
684407	NM_018116.4(MSTO1):c.651C>G (p.Phe217Leu)	MSTO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
972913	NM_004614.5(TK2):c.659T>C (p.Leu220Pro)	TK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
370063	NC_012920.1(MT-CYB):m.15096T>C	MT-CYB	Uncertain significance	no assertion criteria provided
162369	NC_012920.1(MT-TA):m.5631G>A	MT-TA	Uncertain significance	reviewed by expert panel
162370	NC_012920.1(MT-TA):m.5610G>A	MT-TA	Uncertain significance	reviewed by expert panel
9625	NC_012920.1(MT-TA):m.5591G>A	MT-TA	Uncertain significance	reviewed by expert panel
9587	NC_012920.1(MT-TL2):m.12320A>G	MT-TL2	Uncertain significance	reviewed by expert panel
9578	NC_012920.1(MT-TM):m.4409T>C	MT-TM	Uncertain significance	reviewed by expert panel
138857	NM_025215.6(PUS1):c.345C>T (p.Asp115=)	LOC132090059	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138859	NM_025215.6(PUS1):c.397G>A (p.Asp133Asn)	LOC132090059	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138853	NM_025215.6(PUS1):c.999G>C (p.Leu333=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138854	NM_025215.6(PUS1):c.1197C>T (p.Phe399=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138858	NM_025215.6(PUS1):c.364C>A (p.Arg122=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
215035	NM_025215.6(PUS1):c.621G>A (p.Thr207=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
512031	NM_025215.6(PUS1):c.1065G>T (p.Pro355=)	PUS1	Likely benign	criteria provided, multiple submitters, no conflicts
721364	NM_025215.6(PUS1):c.1047C>T (p.Asn349=)	PUS1	Likely benign	criteria provided, multiple submitters, no conflicts
4279939	NM_001031734.3:c.115G>T	FDX2	not provided	no classification provided
3766418	NM_178526.5(SLC25A42):c.809C>A (p.Thr270Lys)	SLC25A42	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 18 · 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
FDX2	Strong	Autosomal recessive	mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC25A4	Orphanet:1369	Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome
SLC25A4	Orphanet:254892	Autosomal dominant progressive external ophthalmoplegia
TK2	Orphanet:254875	Mitochondrial DNA depletion syndrome, myopathic form
TK2	Orphanet:254886	Autosomal recessive progressive external ophthalmoplegia
PUS1	Orphanet:2598	Mitochondrial myopathy and sideroblastic anemia
LARS2	Orphanet:528091	Hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome
LARS2	Orphanet:642945	Perrault syndrome type 1
LARS2	Orphanet:642976	Perrault syndrome type 2
MSTO1	Orphanet:502423	Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome
MT-CYB	Orphanet:104	Leber hereditary optic neuropathy
MT-CYB	Orphanet:137675	Histiocytoid cardiomyopathy
MT-CYB	Orphanet:1460	Isolated complex III deficiency
MT-TE	Orphanet:254864	Mitochondrial myopathy with reversible cytochrome C oxidase deficiency
MT-TE	Orphanet:2596	Myopathy and diabetes mellitus
MT-TL2	Orphanet:2131	Alternating hemiplegia of childhood
MT-TL2	Orphanet:663	Mitochondrial DNA-related progressive external ophthalmoplegia
MT-TW	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TW	Orphanet:550	MELAS

Cohort genes → proteins

13 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FDX2	HGNC:30546	ENSG00000267673	Q6P4F2	Ferredoxin-2, mitochondrial	gencc,clinvar
SLC25A4	HGNC:10990	ENSG00000151729	P12235	ADP/ATP translocase 1	clinvar
TK2	HGNC:11831	ENSG00000166548	O00142	Thymidine kinase 2, mitochondrial	clinvar
PUS1	HGNC:15508	ENSG00000177192	Q9Y606	Pseudouridylate synthase 1 homolog	clinvar
LARS2	HGNC:17095	ENSG00000011376	Q15031	Leucine–tRNA ligase, mitochondrial	clinvar
SLC25A42	HGNC:28380	ENSG00000181035	Q86VD7	Mitochondrial coenzyme A transporter SLC25A42	clinvar
MSTO1	HGNC:29678	ENSG00000125459	Q9BUK6	Protein misato homolog 1	clinvar
MT-CYB	HGNC:7427	ENSG00000198727	P00156	Cytochrome b	clinvar
MT-TA	HGNC:7475	ENSG00000210127		mitochondrially encoded tRNA-Ala (GCN)	clinvar
MT-TE	HGNC:7479	ENSG00000210194		mitochondrially encoded tRNA-Glu (GAA/G)	clinvar
MT-TL2	HGNC:7491	ENSG00000210191		mitochondrially encoded tRNA-Leu (CUN) 2	clinvar
MT-TM	HGNC:7492	ENSG00000210112		mitochondrially encoded tRNA-Met (AUA/G)	clinvar
MT-TW	HGNC:7501	ENSG00000210117		mitochondrially encoded tRNA-Trp (UGA/G)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FDX2	Ferredoxin-2, mitochondrial	Electron donor, of the core iron-sulfur cluster (ISC) assembly complex, that acts to reduce the persulfide into sulfide during [2Fe-2S] clusters assembly on the scaffolding protein ISCU.
SLC25A4	ADP/ATP translocase 1	ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell.
TK2	Thymidine kinase 2, mitochondrial	Phosphorylates thymidine, deoxycytidine, and deoxyuridine in the mitochondrial matrix.
PUS1	Pseudouridylate synthase 1 homolog	Pseudouridylate synthase that catalyzes pseudouridylation of tRNAs and mRNAs.
LARS2	Leucine–tRNA ligase, mitochondrial	Catalyzes the attachment of leucine to its cognate tRNA.
SLC25A42	Mitochondrial coenzyme A transporter SLC25A42	Mitochondrial carrier mediating the transport of coenzyme A (CoA) in mitochondria in exchange for intramitochondrial (deoxy)adenine nucleotides and adenosine 3’,5’-diphosphate.
MSTO1	Protein misato homolog 1	Involved in the regulation of mitochondrial distribution and morphology.
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.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 10 · Druggable fraction: 0.23

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
Other/Unknown	10	1.4×	0.309
Kinase	1	2.1×	0.380
Enzyme (other)	2	1.8×	0.380

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FDX2	Other/Unknown	no		2Fe-2S_ferredoxin-type, Adrenodoxin-like, Beta-grasp_dom_sf
SLC25A4	Other/Unknown	no		MCP, ADT_euk_type, MCP_transmembrane
TK2	Kinase	yes	2.7.1.21	DCK/DGK, P-loop_NTPase, DNK_dom
PUS1	Enzyme (other)	yes	5.4.99.B22	PsdUridine_synth_TruA, TruA/RsuA/RluB/E/F_N, PsdUridine_synth_TruA_C
LARS2	Enzyme (other)	yes	6.1.1.4	aa-tRNA-synth_I_CS, aa-tRNA-synth_Ia, Leu-tRNA-ligase
SLC25A42	Other/Unknown	no		MCP, GDC-like, DNA_mismatch_repair_CS
MSTO1	Other/Unknown	no		Misato_II_tubulin-like, DML1/Misato_tubulin, Tubulin/FtsZ_GTPase_sf
MT-CYB	Other/Unknown	no		Cyt_b/b6_N, Cyt_b/b6_C, Di-haem_cyt_TM
MT-TA	Other/Unknown	no
MT-TE	Other/Unknown	no
MT-TL2	Other/Unknown	no
MT-TM	Other/Unknown	no
MT-TW	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

9 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	6
sural nerve	3
prefrontal cortex	2
adrenal tissue	2
skeletal muscle tissue	2
caudate nucleus	2
anterior cingulate cortex	1
frontal cortex	1
heart right ventricle	1
left ventricle myocardium	1
calcaneal tendon	1
granulocyte	1
lower esophagus mucosa	1
mucosa of transverse colon	1
oocyte	1
ventricular zone	1
gastrocnemius	1
right lobe of liver	1
vena cava	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FDX2	134	ubiquitous	marker	prefrontal cortex, frontal cortex, anterior cingulate cortex
SLC25A4	292	ubiquitous	marker	left ventricle myocardium, heart right ventricle, apex of heart
TK2	280	ubiquitous	marker	calcaneal tendon, sural nerve, adrenal tissue
PUS1	229	ubiquitous	marker	granulocyte, mucosa of transverse colon, lower esophagus mucosa
LARS2	285	ubiquitous	yes	ventricular zone, oocyte, adrenal tissue
SLC25A42	225	ubiquitous	marker	right lobe of liver, gastrocnemius, vena cava
MSTO1	134	tissue_specific	marker	left testis, right testis, testis
MT-CYB	134	ubiquitous	marker	apex of heart, pituitary gland, zone of skin
MT-TA	118		yes	skeletal muscle tissue, duodenum, apex of heart
MT-TE	118	broad	marker	skeletal muscle tissue, sural nerve, apex of heart
MT-TL2	118	broad	yes	apex of heart, putamen, caudate nucleus
MT-TM	118		marker	prefrontal cortex, apex of heart, caudate nucleus
MT-TW	114	ubiquitous	yes	sural nerve, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LARS2	3,406
MT-CYB	3,317
SLC25A4	3,085
PUS1	2,688
FDX2	2,374
TK2	2,031
SLC25A42	1,892
MSTO1	1,025
MT-TA	0
MT-TE	0

Intra-cohort edges

A	B	Sources
PUS1	SLC25A42	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 5 · No structure: 5

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PUS1	Q9Y606	6
FDX2	Q6P4F2	5
MT-CYB	P00156	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A4	P12235	92.07
SLC25A42	Q86VD7	90.95
LARS2	Q15031	90.57
TK2	O00142	85.01
MSTO1	Q9BUK6	83.83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 36. Enrichment computed across 13 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial Uncoupling	1	815.7×	0.027	SLC25A4
Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization	1	543.8×	0.027	SLC25A4
Electron transport from NADPH to Ferredoxin	1	407.9×	0.027	FDX2
Defective CYP11A1 causes AICSR	1	326.3×	0.027	FDX2
Interactions of Vpr with host cellular proteins	1	203.9×	0.027	SLC25A4
Nucleotide salvage	1	163.1×	0.027	TK2
tRNA modification in the mitochondrion	1	148.3×	0.027	PUS1
Pyrimidine salvage	1	148.3×	0.027	TK2
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	135.9×	0.027	SLC25A4
Mitochondrial iron-sulfur cluster biogenesis	1	116.5×	0.027	FDX2
Pregnenolone biosynthesis	1	116.5×	0.027	FDX2
Vitamin B5 (pantothenate) metabolism	1	108.8×	0.027	SLC25A42
Mitochondrial tRNA aminoacylation	1	74.2×	0.037	LARS2
Complex III assembly	1	62.8×	0.040	MT-CYB
Endogenous sterols	1	56.3×	0.040	FDX2
Metabolism	3	5.0×	0.040	SLC25A4, TK2, SLC25A42
Host Interactions of HIV factors	1	48.0×	0.044	SLC25A4
Metabolism of nucleotides	1	42.9×	0.044	TK2
tRNA modification in the nucleus and cytosol	1	41.8×	0.044	PUS1
tRNA Aminoacylation	1	40.8×	0.044	LARS2
Transport of vitamins, nucleosides, and related molecules	1	38.8×	0.044	SLC25A4
Protein localization	1	27.2×	0.059	SLC25A4
Metabolism of water-soluble vitamins and cofactors	1	25.9×	0.059	SLC25A42
Mitochondrial protein import	1	24.0×	0.061	SLC25A4
HIV Infection	1	17.0×	0.081	SLC25A4
Metabolism of vitamins and cofactors	1	16.6×	0.081	SLC25A42
Mitochondrial translation termination	1	15.7×	0.083	MT-CYB
Respiratory electron transport	1	13.6×	0.092	MT-CYB
Aerobic respiration and respiratory electron transport	1	12.7×	0.095	SLC25A4
Translation	1	8.9×	0.129	LARS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ADP transport	2	526.6×	3e-04	SLC25A4, SLC25A42
coenzyme A transmembrane transport	1	2106.5×	0.005	SLC25A42
deoxycytidine metabolic process	1	2106.5×	0.005	TK2
AMP transport	1	2106.5×	0.005	SLC25A42
response to D-galactosamine	1	2106.5×	0.005	MT-CYB
leucyl-tRNA aminoacylation	1	1053.2×	0.006	LARS2
response to cobalamin	1	1053.2×	0.006	MT-CYB
pyrimidine nucleoside salvage	1	1053.2×	0.006	TK2
thymidine metabolic process	1	1053.2×	0.006	TK2
mitochondrial tRNA pseudouridine synthesis	1	702.2×	0.007	PUS1
P450-containing electron transport chain	1	702.2×	0.007	FDX2
electron transport coupled proton transport	1	526.6×	0.008	MT-CYB
positive regulation of mitochondrial fusion	1	421.3×	0.008	MSTO1
[4Fe-4S] cluster assembly	1	421.3×	0.008	FDX2
mitochondrial ADP transmembrane transport	1	421.3×	0.008	SLC25A4
tRNA pseudouridine synthesis	1	351.1×	0.009	PUS1
response to mercury ion	1	300.9×	0.010	MT-CYB
pantothenate metabolic process	1	263.3×	0.011	SLC25A42
mitochondrion distribution	1	263.3×	0.011	MSTO1
mitochondrial ATP transmembrane transport	1	234.1×	0.011	SLC25A4
response to glucagon	1	210.7×	0.011	MT-CYB
mRNA pseudouridine synthesis	1	210.7×	0.011	PUS1
electron transport chain	1	191.5×	0.011	FDX2
response to copper ion	1	191.5×	0.011	MT-CYB
ATP transport	1	175.5×	0.011	SLC25A42
[2Fe-2S] cluster assembly	1	175.5×	0.011	FDX2
regulation of mitochondrial membrane permeability	1	175.5×	0.011	SLC25A4
mitochondrial electron transport, ubiquinol to cytochrome c	1	162.0×	0.012	MT-CYB
response to hyperoxia	1	140.4×	0.013	MT-CYB
positive regulation of mitophagy	1	140.4×	0.013	SLC25A4

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Elamipretide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Nicotinamide Riboside.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 12

Druggability breadth: 4 of 13 evidence-associated genes (31%) 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
TK2	SORIVUDINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TK2	1	4
FDX2	0	0
SLC25A4	0	0
PUS1	0	0
LARS2	0	0
SLC25A42	0	0
MSTO1	0	0
MT-CYB	0	0
MT-TA	0	0
MT-TE	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SORIVUDINE	4	TK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
TK2	17	Binding:17
PUS1	6	Binding:6
SLC25A4	1	Binding:1
LARS2	1	ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TK2	2.7.1.21	thymidine kinase
PUS1	5.4.99.B22
LARS2	6.1.1.4	leucine-tRNA ligase

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
SORIVUDINE	4	TK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TK2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PUS1
D	Druggable family + AlphaFold only, no drug	1	LARS2
E	Difficult family or no structure, no drug	10	FDX2, SLC25A4, SLC25A42, MSTO1, MT-CYB, MT-TA, MT-TE, MT-TL2, MT-TM, MT-TW

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FDX2	0	—
SLC25A4	1	—
PUS1	6	—
LARS2	1	—
SLC25A42	0	—
MSTO1	0	—
MT-CYB	0	—
MT-TA	0	—
MT-TE	0	—
MT-TL2	0	—
MT-TM	0	—
MT-TW	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 40.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	20
PHASE2	9
PHASE1	6
PHASE3	2
PHASE1/PHASE2	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03323749	PHASE3	TERMINATED	A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT05267574	PHASE2/PHASE3	TERMINATED	An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead)
NCT05590468	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate Vitamin B3 Derivative to Treat Mitochondrial Myopathy
NCT06754098	PHASE2	RECRUITING	Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency
NCT00457314	PHASE2	UNKNOWN	The Effects of Exercise Versus Inactivity on People With Mitochondrial Muscle Disease
NCT02255422	PHASE2	COMPLETED	RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR
NCT02367014	PHASE1/PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04535609	PHASE2	COMPLETED	An Efficacy and Safety Study of 24 Week Treatment With Mavodelpar (REN001) in Primary Mitochondrial Myopathy Patients
NCT04641962	PHASE2	TERMINATED	A Study to Evaluate ASP0367 in Participants With Primary Mitochondrial Myopathy
NCT05962333	PHASE2	UNKNOWN	Effect and Safety MABs Administration m.3243A>G Mutation Carriers
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT03862846	PHASE1	TERMINATED	A Study of the Safety of REN001 in Patients With Primary Mitochondrial Myopathy
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT05063721	PHASE1	COMPLETED	MABs Therapy m.3243A>G Mutation Carriers
NCT05199740	Not specified	RECRUITING	mtDNA Mutation Load Analysis in Mesoangioblasts
NCT05346627	Not specified	RECRUITING	Home Based Personalized Training and Video Consultation in Mitochondrial Myopathies: Study of Efficacy and Tolerance.
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT07450690	Not specified	RECRUITING	Exercise Training Effects on Muscle Function in Adults With Mitochondrial Myopathy
NCT07478172	Not specified	RECRUITING	Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
NCT00004353	Not specified	COMPLETED	Study of the Metabolism of Pyruvate and Related Problems in Patients With Lactic Acidemia
NCT00004770	Not specified	COMPLETED	Pilot Compassionate Use Study of Thioctic Acid Treatment in Mitochondrial Myopathy
NCT02375438	Not specified	COMPLETED	Nutritional Assessment in Mitochondrial Cytopathy
NCT02895789	Not specified	COMPLETED	Oxidative Capacity and Exercise Tolerance in Ambulatory SMA
NCT03432871	Not specified	COMPLETED	Nicotinamide Riboside and Mitochondrial Biogenesis
NCT03513835	Not specified	COMPLETED	Diagnostic Screening Tests and Potential Biomarkers in Mitochondrial Myopathies
NCT03728777	Not specified	COMPLETED	Resveratrol Supplementation in Patients With Mitochondrial Myopathies and Skeletal Muscle Fatty Acid Oxidation Disorders
NCT03973203	Not specified	COMPLETED	Niacin Supplementation in Healthy Controls and Mitochondrial Myopathy Patients
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NCT05012358	Not specified	COMPLETED	Genomic Profiling of Mitochondrial Disease - Imaging Analysis for Precise Mitochondrial Medicine
NCT05199246	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Lower-limb Powered Dermoskeleton in Patients With Neuromuscular Disorders
NCT05200702	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Knee-hip Powered Soft Exoskeleton in Patients With Neuromuscular Disorders
NCT06080568	Not specified	COMPLETED	Human Mitochondrial Stress-driven Obesity Resistance
NCT06080581	Not specified	COMPLETED	Mitochondrial Dysfunctions Driving Insulin Resistance
NCT06080594	Not specified	COMPLETED	Exercise-mediated Rescue of Mitochondrial Dysfunctions Driving Insulin Resistance

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OMAVELOXOLONE	4	1
ELAMIPRETIDE	3	2
NICOTINAMIDE RIBOSIDE	3	2
SONLICROMANOL	3	2
LIPOIC ACID, ALPHA	3	1
RESVERATROL	3	1
MAVODELPAR	2	3
BOCIDELPAR	2	1
DOXECITINE	2	1
DOXRIBTIMINE	2	1
NAPAZIMONE	2	1
CHEMBL1234071	0	1
THIOCTIC ACID	0	1

Cohort genes: FDX2, SLC25A4, TK2, PUS1, LARS2, SLC25A42, MSTO1, MT-CYB, MT-TA, MT-TE, MT-TL2, MT-TM, MT-TW
Drugs: Omaveloxolone, Elamipretide, Nicotinamide Riboside, Sonlicromanol, Lipoic Acid, Alpha, Resveratrol