TIMM22

Summary

TIMM22 (translocase of inner mitochondrial membrane 22, HGNC:17317) is a protein-coding gene on chromosome 17p13, encoding Mitochondrial import inner membrane translocase subunit Tim22 (Q9Y584). Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. It is a selective cancer dependency (DepMap: 53.9% of cell lines).

Multipass transmembrane proteins are brought into mitochondria and inserted into the mitochondrial inner membrane by way of the TIM22 complex. This complex has six subunits and is a twin-pore translocase. The protein encoded by this gene is a subunit of TIM22 and represents the voltage-activated and signal-gated channel.

Source: NCBI Gene 29928 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Moderate, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 46 total — 2 pathogenic
• Phenotypes (HPO): 14
• Cancer dependency (DepMap): dependent in 53.9% of screened cell lines
• MANE Select transcript: NM_013337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17317
Approved symbol	TIMM22
Name	translocase of inner mitochondrial membrane 22
Location	17p13
Locus type	gene with protein product
Status	Approved
Aliases	TIM22
Ensembl gene	ENSG00000177370
Ensembl biotype	protein_coding
OMIM	607251
Entrez	29928

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000327158, ENST00000857801

RefSeq mRNA: 1 — MANE Select: NM_013337 NM_013337

CCDS: CCDS32521

Canonical transcript exons

ENST00000327158 — 4 exons

Exon	Start	End
ENSE00001250075	999512	999584
ENSE00001250082	998779	998975
ENSE00001250095	1001012	1003671
ENSE00001250104	997129	997380

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 85.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.4772 / max 187.1104, expressed in 1814 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158697	32.4772	1814

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	85.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.52	gold quality
heart left ventricle	UBERON:0002084	84.74	gold quality
heart	UBERON:0000948	82.96	gold quality
islet of Langerhans	UBERON:0000006	82.66	gold quality
gastrocnemius	UBERON:0001388	82.50	gold quality
muscle of leg	UBERON:0001383	82.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.30	gold quality
placenta	UBERON:0001987	82.21	gold quality
right atrium auricular region	UBERON:0006631	81.78	gold quality
prefrontal cortex	UBERON:0000451	81.41	gold quality
stromal cell of endometrium	CL:0002255	81.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.18	gold quality
lower esophagus	UBERON:0013473	81.15	gold quality
left adrenal gland	UBERON:0001234	80.85	gold quality
right adrenal gland	UBERON:0001233	80.72	gold quality
skeletal muscle tissue	UBERON:0001134	80.67	gold quality
frontal cortex	UBERON:0001870	80.65	gold quality
mucosa of transverse colon	UBERON:0004991	80.61	gold quality
right adrenal gland cortex	UBERON:0035827	80.53	gold quality
left adrenal gland cortex	UBERON:0035825	80.44	gold quality
cortical plate	UBERON:0005343	80.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.15	gold quality
adrenal gland	UBERON:0002369	80.03	gold quality
anterior cingulate cortex	UBERON:0009835	79.91	gold quality
adult mammalian kidney	UBERON:0000082	79.83	gold quality
superior frontal gyrus	UBERON:0002661	79.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.80	gold quality
cerebral cortex	UBERON:0000956	79.79	gold quality
hypothalamus	UBERON:0001898	79.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.13
E-MTAB-7303	no	603.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting TIMM22, 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-4650-5P	99.98	64.69	999
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-203B-3P	97.82	66.27	979
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-7976	95.75	65.67	1186

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 53.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• in contrast to yeast, only a small fraction of Tim9-Tim10a-Tim10b complex is in a stable association with Tim22. (PMID:14726512)
• The dual function of AGK as lipid kinase and constituent of the TIM22 complex reveals that disturbances in both phospholipid metabolism and mitochondrial protein biogenesis contribute to the pathogenesis of Sengers syndrome. (PMID:28712724)
• Identify AGK as a bona fide subunit of TIM22 providing an exciting and unexpected link between mitochondrial protein import and Sengers syndrome. (PMID:28712726)
• The human TIM22 complex associates with the mitochondrial contact site and cristae organizing system (MICOS) complex. (PMID:31103774)
• Defining the Substrate Spectrum of the TIM22 Complex Identifies Pyruvate Carrier Subunits as Unconventional Cargos. (PMID:32142709)
• Biogenesis of Mitochondrial Metabolite Carriers. (PMID:32645990)
• Cryo-EM structure of the human mitochondrial translocase TIM22 complex. (PMID:32901109)
• Defining the architecture of the human TIM22 complex by chemical crosslinking. (PMID:33125709)
• The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism. (PMID:33476211)
• TIM22 and TIM29 inhibit HBV replication by up-regulating SRSF1 expression. (PMID:38294104)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	TIMM22	ENSDARG00000091413
mus_musculus	Timm22	ENSMUSG00000020843
rattus_norvegicus	Timm22	ENSRNOG00000007988
drosophila_melanogaster	CG31229	FBGN0051229
caenorhabditis_elegans		WBGENE00008164

Protein

Protein identifiers

Mitochondrial import inner membrane translocase subunit Tim22 — Q9Y584 (reviewed: Q9Y584)

Alternative names: Testis-expressed protein 4

All UniProt accessions (1): Q9Y584

UniProt curated annotations — full annotation on UniProt →

Function. Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps.

Subunit / interactions. Component of the TIM22 complex, whose core is composed of TIMM22, associated with peripheral protein FXC1/TIMM10B and the 70 kDa heterohexamer. In most cases, the 70 kDa complex is composed of TIMM9 and TIMM10 (TIMM10A or TIMM10B). A small fraction of the 70 kDa complex is composed of TIMM8 (TIMM8A/DDP1 or TIMM8B/DDP2) and TIMM13. The TIM22 complex also contains AGK and TIMM29. Interacts directly with TIMM9, TIMM10A and FXC1/TIMM10B. Interacts (when oxidized) with TIMM29; interaction is direct.

Subcellular location. Mitochondrion inner membrane.

Post-translational modifications. Disulfide bonds promote efficient assembly of the TIM22 complex.

Disease relevance. Combined oxidative phosphorylation deficiency 43 (COXPD43) [MIM:618851] An autosomal recessive mitochondrial disorder characterized by onset at birth, intrauterine growth retardation, hypotonia, myopathy, feeding difficulties associated with gastroesophageal reflux, and persistently elevated serum lactate and creatine kinase. Brain imaging shows delayed myelination. Muscle biopsy shows decreased activities of mitochondrial respiratory chain complexes I, III, and IV. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Tim17/Tim22/Tim23 family.

RefSeq proteins (1): NP_037469* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039175	TIM22	Family

Pfam: PF02466

UniProt features (13 total): sequence conflict 5, transmembrane region 3, disulfide bond 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7CGP	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y584-F1	79.82	0.44

Functional residue map

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

Disulfide bonds (2): 69–141, 160–179

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-9837999	Mitochondrial protein degradation

MSigDB gene sets: 164 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, IGLESIAS_E2F_TARGETS_UP, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GRADE_COLON_AND_RECTAL_CANCER_DN, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (3): protein insertion into mitochondrial inner membrane (GO:0045039), protein transport (GO:0015031), protein transmembrane transport (GO:0071806)

GO Molecular Function (4): transmembrane protein transporter activity (GO:0008320), mitochondrion targeting sequence binding (GO:0030943), protein transporter activity (GO:0140318), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), TIM22 mitochondrial import inner membrane insertion complex (GO:0042721), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inner mitochondrial membrane organization	1
mitochondrial protein import pathway	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein transport	1
transmembrane transport	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
signal sequence receptor activity	1
transporter activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
inner mitochondrial membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIMM22	TIMM9	Q9Y5J7	897
TIMM22	TIMM10	P62072	895
TIMM22	TIMM23	O14925	838
TIMM22	TIMM29	Q9BSF4	835
TIMM22	TIMM50	Q3ZCQ8	814
TIMM22	YWHAE	P29360	793
TIMM22	BHLHA9	Q7RTU4	770
TIMM22	TRARG1	Q8IXB3	770
TIMM22	PITPNA	Q00169	751
TIMM22	TIMM44	O43615	750
TIMM22	TIMM17A	Q99595	716
TIMM22	SCARF1	Q14162	714
TIMM22	TIMM10B	Q9Y5J6	706
TIMM22	TIMM13	P62206	680
TIMM22	PAFAH1B1	P43034	672

IntAct

12 interactions, top by confidence:

A	B	Type	Score
TIMM9	TIMM10	psi-mi:“MI:0914”(association)	0.830
TIMM10B	TIMM10	psi-mi:“MI:0914”(association)	0.710
CYSRT1	TIMM22	psi-mi:“MI:0915”(physical association)	0.560
REEP4	TIMM22	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	TIMM22	psi-mi:“MI:0915”(physical association)	0.560
TIMM22	TIMM10	psi-mi:“MI:0914”(association)	0.350
TIMM22	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
TIMM22	REEP4	psi-mi:“MI:0915”(physical association)	0.000
TIMM22	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): TIMM22 (Affinity Capture-RNA), TIMM22 (Synthetic Lethality), TIMM22 (Affinity Capture-Western), TIMM22 (Positive Genetic), TIMM22 (Positive Genetic), TIMM22 (Positive Genetic), TIMM22 (Positive Genetic), TIMM22 (Negative Genetic), TIMM22 (Negative Genetic), TIMM22 (Affinity Capture-MS), TIMM22 (Affinity Capture-Western), TIMM22 (Two-hybrid), TIMM22 (Two-hybrid), CYSRT1 (Two-hybrid), TIMM22 (Negative Genetic)

ESM2 similar proteins: A2RVP7, A2VDV9, A4IFL0, O14925, O35093, O35094, O35857, O43615, O60830, P0CR88, P0CR89, P59670, Q02921, Q2HJE9, Q2KHV4, Q2UAP8, Q38820, Q3B8P0, Q3ZBE6, Q4V8S3, Q5BIN4, Q5M7K0, Q5R5H4, Q5RDD0, Q5REX0, Q5SRD1, Q5U4F4, Q5U4U5, Q5XH94, Q5XJY4, Q5ZLL0, Q6BZY4, Q6GQ39, Q6INU6, Q6NWD4, Q7T2P6, Q86UB9, Q9C1E8, Q9CQ85, Q9CYV5

Diamond homologs: A0A1D8PI78, A1XJK0, A2RVP7, P0CR88, P0CR89, P87146, Q12328, Q2UAP8, Q54K35, Q54QM0, Q5BIN4, Q5M7K0, Q5U4U5, Q6BT35, Q6BZY4, Q6CRJ6, Q6FT37, Q75E80, Q8IN78, Q9C1E8, Q9CQ85, Q9JKW1, Q9NAQ9, Q9Y584, Q9Z0V7, Q6NKU9, Q94EH2, O35092, O44477, O48528, O60830, Q2HJE9, Q99595, Q9Z0V8, P39515, P59670, P87130, Q9LN27, Q9LNQ1, Q9LYG1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TIMM22	“form complex”	“TIM22 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1808625	GRCh37/hg19 17p13.3(chr17:526-1690452)x1	Pathogenic
869638	NM_013337.4(TIMM22):c.75C>A (p.Tyr25Ter)	Pathogenic

SpliceAI

620 predictions. Top by Δscore:

Variant	Effect	Δscore
17:997378:G:GT	donor_gain	1.0000
17:997380:GGTG:G	donor_loss	1.0000
17:997381:G:GA	donor_loss	1.0000
17:998877:G:GT	donor_gain	1.0000
17:998905:G:GT	donor_gain	1.0000
17:998906:A:T	donor_gain	1.0000
17:998937:G:GT	donor_gain	1.0000
17:998971:AATCT:A	donor_gain	1.0000
17:998972:ATCT:A	donor_gain	1.0000
17:998973:TCT:T	donor_gain	1.0000
17:998974:CT:C	donor_gain	1.0000
17:998974:CTGTA:C	donor_loss	1.0000
17:998975:TGTA:T	donor_loss	1.0000
17:998976:G:C	donor_loss	1.0000
17:998976:G:GG	donor_gain	1.0000
17:998977:TAAGT:T	donor_loss	1.0000
17:998978:AA:A	donor_loss	1.0000
17:999507:CACA:C	acceptor_loss	1.0000
17:999510:A:AG	acceptor_gain	1.0000
17:999510:A:C	acceptor_loss	1.0000
17:999511:G:GA	acceptor_gain	1.0000
17:999511:GT:G	acceptor_gain	1.0000
17:999511:GTACC:G	acceptor_gain	1.0000
17:997342:A:T	donor_gain	0.9900
17:997346:C:G	donor_gain	0.9900
17:997359:GC:G	donor_gain	0.9900
17:997378:G:T	donor_gain	0.9900
17:997382:T:G	donor_loss	0.9900
17:998777:A:AG	acceptor_gain	0.9900
17:998777:AG:A	acceptor_gain	0.9900

AlphaMissense

1246 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:998791:G:A	G84E	1.000
17:999564:G:A	G163E	1.000
17:1001036:G:A	G178D	0.999
17:1001045:G:A	G181D	0.999
17:1001047:T:C	F182L	0.999
17:1001049:T:A	F182L	0.999
17:1001049:T:G	F182L	0.999
17:1001051:C:A	A183D	0.999
17:1001054:C:A	A184D	0.999
17:998779:G:A	G80E	0.999
17:998785:T:A	V82D	0.999
17:998790:G:A	G84R	0.999
17:998790:G:C	G84R	0.999
17:998797:C:A	A86E	0.999
17:998803:G:A	G88E	0.999
17:998917:C:A	A126D	0.999
17:998929:C:A	A130D	0.999
17:998938:G:A	G133E	0.999
17:998946:T:C	F136L	0.999
17:998948:T:A	F136L	0.999
17:998948:T:G	F136L	0.999
17:999548:A:C	S158R	0.999
17:999550:T:A	S158R	0.999
17:999550:T:G	S158R	0.999
17:999552:G:A	G159D	0.999
17:999554:T:C	C160R	0.999
17:999576:G:A	G167D	0.999
17:1001038:T:C	C179R	0.998
17:997371:T:C	C77R	0.998
17:998794:G:A	G85D	0.998

dbSNP variants (sampled 300 via entrez): RS1000283021 (17:996868 C>A,G), RS1000336020 (17:996656 G>A), RS1000952754 (17:995909 A>C), RS1001180088 (17:1002225 G>GA), RS1001232458 (17:1001982 T>C), RS1001368886 (17:1003695 A>G), RS1001534298 (17:998318 A>G), RS1001587870 (17:1003994 C>T), RS1001693508 (17:997245 G>A), RS1001915590 (17:999995 G>C), RS1002263335 (17:999788 C>G,T), RS1002855395 (17:1003278 G>A), RS1003694354 (17:1002488 C>T), RS1003873827 (17:998350 G>A), RS1004257510 (17:998832 G>A,T)

Disease associations

OMIM: gene MIM:607251 | disease phenotypes: MIM:618851

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial disease	Moderate	Autosomal recessive
combined oxidative phosphorylation deficiency 43	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (2): combined oxidative phosphorylation deficiency 43 (MONDO:0030017), mitochondrial disease (MONDO:0044970)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001319	Neonatal hypotonia
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0002020	Gastroesophageal reflux
HP:0002151	Increased circulating lactate concentration
HP:0002188	Delayed CNS myelination
HP:0002587	Projectile vomiting
HP:0003236	Elevated circulating creatine kinase concentration
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0008807	Acetabular dysplasia
HP:0008872	Feeding difficulties in infancy
HP:0011923	Decreased activity of mitochondrial complex I
HP:0011924	Decreased activity of mitochondrial complex III

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
arsenite	increases methylation	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Dexamethasone	increases expression, affects cotreatment	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Paclitaxel	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	decreases expression	1
Lactic Acid	decreases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	EARLY_PHASE1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies