VARS2

Summary

VARS2 (valyl-tRNA synthetase 2, mitochondrial, HGNC:21642) is a protein-coding gene on chromosome 6p21.33, encoding Valine–tRNA ligase, mitochondrial (Q5ST30). Catalyzes the attachment of valine to tRNA(Val) in a two-step reaction: valine is first activated by ATP to form Val-AMP and then transferred to the acceptor end of tRNA(Val). It is a selective cancer dependency (DepMap: 64.5% of cell lines).

This gene encodes a mitochondrial aminoacyl-tRNA synthetase, which catalyzes the attachment of valine to tRNA(Val) for mitochondrial translation. Mutations in this gene cause combined oxidative phosphorylation deficiency-20, and are also associated with early-onset mitochondrial encephalopathies. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 57176 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 529 total — 16 pathogenic, 17 likely-pathogenic
• Cancer dependency (DepMap): dependent in 64.5% of screened cell lines
• MANE Select transcript: NM_020442

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21642
Approved symbol	VARS2
Name	valyl-tRNA synthetase 2, mitochondrial
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434L1435, KIAA1885, G7a
Ensembl gene	ENSG00000137411
Ensembl biotype	protein_coding
OMIM	612802
Entrez	57176

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000321897, ENST00000421263, ENST00000428017, ENST00000467717, ENST00000469358, ENST00000473916, ENST00000476162, ENST00000477052, ENST00000490699, ENST00000541562, ENST00000625423, ENST00000672801, ENST00000676266, ENST00000897142, ENST00000897143, ENST00000924206, ENST00000924207, ENST00000924208, ENST00000947399

RefSeq mRNA: 3 — MANE Select: NM_020442 NM_001167733, NM_001167734, NM_020442

CCDS: CCDS34387, CCDS54981

Canonical transcript exons

ENST00000383369 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0208 / max 132.3323, expressed in 1732 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66837	6.3256	1690
66838	1.0259	606
203939	0.3824	152
66843	0.1294	27
66840	0.0699	22
203940	0.0444	13
66842	0.0230	8
66841	0.0204	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.98	gold quality
cerebellar hemisphere	UBERON:0002245	94.97	gold quality
cerebellar cortex	UBERON:0002129	94.94	gold quality
cerebellum	UBERON:0002037	94.92	gold quality
lower esophagus mucosa	UBERON:0035834	93.57	gold quality
ventricular zone	UBERON:0003053	92.10	gold quality
ganglionic eminence	UBERON:0004023	92.08	gold quality
cortical plate	UBERON:0005343	91.93	gold quality
apex of heart	UBERON:0002098	91.05	gold quality
right frontal lobe	UBERON:0002810	90.51	gold quality
esophagus mucosa	UBERON:0002469	90.50	gold quality
right lobe of liver	UBERON:0001114	90.47	gold quality
sural nerve	UBERON:0015488	90.37	gold quality
caudate nucleus	UBERON:0001873	89.80	gold quality
nucleus accumbens	UBERON:0001882	89.80	gold quality
putamen	UBERON:0001874	89.79	gold quality
amygdala	UBERON:0001876	89.53	gold quality
temporal lobe	UBERON:0001871	89.46	gold quality
pituitary gland	UBERON:0000007	89.39	gold quality
mucosa of transverse colon	UBERON:0004991	89.32	gold quality
metanephros cortex	UBERON:0010533	89.26	gold quality
anterior cingulate cortex	UBERON:0009835	89.15	gold quality
adenohypophysis	UBERON:0002196	89.03	gold quality
hypothalamus	UBERON:0001898	88.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.76	gold quality
Ammon’s horn	UBERON:0001954	88.49	gold quality
brain	UBERON:0000955	88.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.40	gold quality
cortex of kidney	UBERON:0001225	88.38	gold quality
primary visual cortex	UBERON:0002436	88.38	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting VARS2, 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-548AR-3P	99.85	71.26	3889
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-6891-3P	95.80	65.76	683

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 64.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Data indicate that variations in the levels of VARS2L between tissue types and patients could underlie the difference in clinical presentation between individuals homoplasmic for the 1624C>T MTTV (equivalent to mt-tRNAVal C25U) mutation. (PMID:18400783)
• VARS2 V552V may be considered as a prognostic factor for survival in patients with early breast cancer. (PMID:20503108)
• VARS2 polymorphism significantly associated with chronic hepatitis B in Korean population. (PMID:25404243)
• VARS2 mutation underlies a novel autosomal recessive syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism. (PMID:29137650)
• this gene should be considered in early-onset mitochondrial encephalomyopathies or encephalocardiomyopathies. (PMID:29314548)
• The novel compound heterozygous pathogenic VARS2 mutations c.643 C > T (p. His215Tyr) and c.1354 A > G (p. Met452Val) has been reported in a female infant. These heterozygous mutations were carried individually by the proband’s parents and elder sister. (PMID:30458719)
• report two additional cases of two non-related young girls from Sardinia, born from non-consanguineous and healthy parents, carrying the aforesaid homozygous VARS2 variant. At onset both the patients presented with worsening psychomotor delay, muscle hypotonia and brisk tendon reflexes (PMID:31064326)
• Study shows A combination of two novel VARS2 variants causes a mitochondrial disorder associated with failure to thrive and pulmonary hypertension (PMID:31529142)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vars2	ENSDARG00000056717
mus_musculus	Vars2	ENSMUSG00000038838
rattus_norvegicus	Vars2	ENSRNOG00000000833

Paralogs (7): LARS2 (ENSG00000011376), IARS2 (ENSG00000067704), LARS1 (ENSG00000133706), MARS1 (ENSG00000166986), IARS1 (ENSG00000196305), VARS1 (ENSG00000204394), MARS2 (ENSG00000247626)

Protein

Protein identifiers

Valine–tRNA ligase, mitochondrial — Q5ST30 (reviewed: Q5ST30)

Alternative names: Valyl-tRNA synthetase, Valyl-tRNA synthetase-like

All UniProt accessions (4): Q5ST30, A0A0A0MTG1, A2ABL6, B7ZCJ6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the attachment of valine to tRNA(Val) in a two-step reaction: valine is first activated by ATP to form Val-AMP and then transferred to the acceptor end of tRNA(Val).

Subcellular location. Mitochondrion.

Disease relevance. Combined oxidative phosphorylation deficiency 20 (COXPD20) [MIM:615917] A disorder due to mitochondrial respiratory chain complex defects. Clinical features are variable and include muscle weakness with hypotonia, central neurological disease with progressive external ophthalmoplegia, ptosis and ataxia, delayed psychomotor development, cardiomyopathy, abnormal liver function, facial dysmorphism, microcephaly and epilepsy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class-I aminoacyl-tRNA synthetase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5ST30-1	1	yes
Q5ST30-2	2
Q5ST30-3	3
Q5ST30-4	4

RefSeq proteins (3): NP_001161205, NP_001161206, NP_065175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001412	aa-tRNA-synth_I_CS	Conserved_site
IPR002300	aa-tRNA-synth_Ia	Domain
IPR002303	Valyl-tRNA_ligase	Family
IPR009008	Val/Leu/Ile-tRNA-synth_edit	Homologous_superfamily
IPR009080	tRNAsynth_Ia_anticodon-bd	Homologous_superfamily
IPR013155	M/V/L/I-tRNA-synth_anticd-bd	Domain
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR033705	Anticodon_Ia_Val	Domain

Pfam: PF00133, PF08264

Catalyzed reactions (Rhea), 1 shown:

• tRNA(Val) + L-valine + ATP = L-valyl-tRNA(Val) + AMP + diphosphate (RHEA:10704)

UniProt features (25 total): sequence variant 11, sequence conflict 4, splice variant 3, short sequence motif 2, transit peptide 1, chain 1, region of interest 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5ST30-F1	87.96	0.70

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): 661

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-379726	Mitochondrial tRNA aminoacylation
R-HSA-379724	tRNA Aminoacylation
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 184 (showing top): GOBP_AMINO_ACID_ACTIVATION, GOBP_TRNA_METABOLIC_PROCESS, GOBP_TRANSLATION, KEGG_AMINOACYL_TRNA_BIOSYNTHESIS, IK2_01, GOBP_REGULATION_OF_TRANSLATIONAL_FIDELITY, REACTOME_MITOCHONDRIAL_TRNA_AMINOACYLATION, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GAVIN_FOXP3_TARGETS_CLUSTER_P6, LEE_RECENT_THYMIC_EMIGRANT, SANSOM_APC_TARGETS_REQUIRE_MYC, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_AMINOACYL_TRNA_DEACYLASE_ACTIVITY, ARNT_01

GO Biological Process (4): valyl-tRNA aminoacylation (GO:0006438), translation (GO:0006412), tRNA aminoacylation for protein translation (GO:0006418), aminoacyl-tRNA metabolism involved in translational fidelity (GO:0106074)

GO Molecular Function (7): aminoacyl-tRNA deacylase activity (GO:0002161), valine-tRNA ligase activity (GO:0004832), ATP binding (GO:0005524), nucleotide binding (GO:0000166), aminoacyl-tRNA ligase activity (GO:0004812), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (2): mitochondrion (GO:0005739), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
tRNA Aminoacylation	1
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity, acting on a tRNA	2
cytoplasm	2
tRNA aminoacylation for protein translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
tRNA aminoacylation	1
tRNA metabolic process	1
regulation of translational fidelity	1
carboxylic ester hydrolase activity	1
aminoacyl-tRNA metabolism involved in translational fidelity	1
deacylase activity	1
aminoacyl-tRNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ligase activity, forming carbon-oxygen bonds	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2401 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VARS2	RARS2	Q5T160	884
VARS2	WARS2	Q9UGM6	879
VARS2	LARS1	Q9P2J5	875
VARS2	WARS1	P23381	857
VARS2	KARS1	Q15046	855
VARS2	PARS2	Q7L3T8	847
VARS2	MARS2	Q96GW9	846
VARS2	MARS1	P56192	844
VARS2	EARS2	Q5JPH6	842
VARS2	QARS1	P47897	840
VARS2	AARS1	P49588	837
VARS2	CARS2	Q9HA77	829
VARS2	TARS2	Q9BW92	827
VARS2	CARS1	P49589	821
VARS2	TARS3	A2RTX5	818

IntAct

57 interactions, top by confidence:

A	B	Type	Score
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
VARS2	ABI1	psi-mi:“MI:0915”(physical association)	0.560
VARS2	ABI3	psi-mi:“MI:0915”(physical association)	0.560
NCK2	VARS2	psi-mi:“MI:0915”(physical association)	0.560
SORBS3	VARS2	psi-mi:“MI:0915”(physical association)	0.560
VARS2	ABI2	psi-mi:“MI:0915”(physical association)	0.560
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
UCK2	IAH1	psi-mi:“MI:0914”(association)	0.530
VARS2	ABI2	psi-mi:“MI:0915”(physical association)	0.370
NDUFS7		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
HTRA2	VWA8	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
AVPR2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
TACSTD2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350
MRPS24	NUDT19	psi-mi:“MI:0914”(association)	0.350
FPR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
BCL2L12	PRORP	psi-mi:“MI:0914”(association)	0.350
KISS1	KLHL26	psi-mi:“MI:0914”(association)	0.350
YARS2	VWA8	psi-mi:“MI:0914”(association)	0.350
AMACR	VWA8	psi-mi:“MI:0914”(association)	0.350
AK4	VWA8	psi-mi:“MI:0914”(association)	0.350
KISS1	HSPA5	psi-mi:“MI:0914”(association)	0.350

BioGRID (132): VARS2 (Two-hybrid), VARS2 (Two-hybrid), VARS2 (Two-hybrid), MAL2 (Two-hybrid), CMTM5 (Two-hybrid), VARS2 (Affinity Capture-MS), VARS2 (Affinity Capture-MS), VARS2 (Affinity Capture-MS), VARS2 (Affinity Capture-MS), VARS2 (Proximity Label-MS), VARS2 (Proximity Label-MS), VARS2 (Proximity Label-MS), VARS2 (Proximity Label-MS), VARS2 (Affinity Capture-MS), VARS2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2MDK8, A0PJX2, A2ACG1, B3DLB3, D3ZBP4, F1MH07, O75038, P0C869, P0DPD7, P0DPE1, P10688, P10895, P21671, P21709, P51178, Q0IID2, Q1LWV7, Q2KJ24, Q3U2A8, Q4KM32, Q4R380, Q4R6L3, Q5RET0, Q5RKI3, Q5ST30, Q5TM74, Q60750, Q684M2, Q68DD2, Q6MG21, Q6NVG1, Q6ZSI9, Q767M3, Q86U10, Q86XP0, Q8C9V1, Q8K3R3, Q8NFF5, Q8R3B1, Q8SPR7

Diamond homologs: A3N2F0, A4G1V2, A5ITI8, A5UBZ9, A5UEN9, A6QHJ8, A6SUQ8, A6U2D1, A7HJX5, A7X383, A8F8Q3, A8Z2I4, A9BIJ7, B0BR94, B0RVI4, B2SPF0, B3GYI3, B7GH39, C4V924, O75005, P07806, P26640, P28350, P43834, P49696, P93736, Q01PF1, Q04462, Q0AIF2, Q0VSA8, Q2FG72, Q2FXR8, Q2YB22, Q3A253, Q3AF87, Q3BP98, Q3JC50, Q3SL86, Q3U2A8, Q474E1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
QRICH1	“up-regulates quantity by expression”	VARS2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	17
Uncertain significance	233
Likely benign	143
Benign	66

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1357313	NM_020442.6(VARS2):c.3004C>T (p.Arg1002Ter)	Pathogenic
141424	NM_020442.6(VARS2):c.1045G>A (p.Ala349Thr)	Pathogenic
141427	NM_020442.6(VARS2):c.1010C>T (p.Thr337Ile)	Pathogenic
1420183	NM_020442.6(VARS2):c.2749C>T (p.Arg917Ter)	Pathogenic
1940105	NM_020442.6(VARS2):c.1563G>A (p.Trp521Ter)	Pathogenic
2272875	NM_020442.6(VARS2):c.1219C>T (p.Arg407Ter)	Pathogenic
2423916	NC_000006.11:g.(?30890861)(30892357_?)del	Pathogenic
2581609	NM_020442.6(VARS2):c.420del (p.Met141fs)	Pathogenic
2784529	NM_020442.6(VARS2):c.571C>T (p.Gln191Ter)	Pathogenic
3255217	NM_020442.6(VARS2):c.667G>T (p.Glu223Ter)	Pathogenic
4699300	NM_020442.6(VARS2):c.2782C>T (p.Arg928Ter)	Pathogenic
4733523	NM_020442.6(VARS2):c.1650G>A (p.Trp550Ter)	Pathogenic
4777421	NM_020442.6(VARS2):c.1562G>A (p.Trp521Ter)	Pathogenic
4848726	NM_020442.6(VARS2):c.1443del (p.Phe481fs)	Pathogenic
933236	NM_020442.6(VARS2):c.1060G>A (p.Asp354Asn)	Pathogenic
997679	NM_020442.6(VARS2):c.2758T>C (p.Tyr920His)	Pathogenic
1029203	NM_020442.6(VARS2):c.2869_2876dup (p.Leu961fs)	Likely pathogenic
1217942	NM_020442.6(VARS2):c.251_270del (p.Tyr84fs)	Likely pathogenic
1333424	NM_020442.6(VARS2):c.2692G>T (p.Glu898Ter)	Likely pathogenic
1483787	NM_020442.6(VARS2):c.1556+1G>A	Likely pathogenic
1708949	NM_020442.6(VARS2):c.1583G>A (p.Trp528Ter)	Likely pathogenic
1805727	NM_020442.6(VARS2):c.1066C>T (p.Arg356Ter)	Likely pathogenic
2443654	NM_020442.6(VARS2):c.3090+2T>A	Likely pathogenic
2577131	NM_020442.6(VARS2):c.1480-2A>G	Likely pathogenic
2788715	NM_020442.6(VARS2):c.671+1G>A	Likely pathogenic
2999211	NM_020442.6(VARS2):c.753+2T>A	Likely pathogenic
3349642	NM_020442.6(VARS2):c.1624del (p.His542fs)	Likely pathogenic
3764574	NM_020442.6(VARS2):c.1258G>A (p.Gly420Arg)	Likely pathogenic
3767165	NM_020442.6(VARS2):c.1349del (p.Gly450fs)	Likely pathogenic
3780784	NM_020442.6(VARS2):c.2785+1G>A	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000838947 (6:30914276 G>A), RS1001893588 (6:30915474 G>A), RS1002241847 (6:30915932 G>A), RS1002261656 (6:30917622 G>A), RS1002475154 (6:30915633 C>G,T), RS1003302718 (6:30923733 T>C), RS1003417363 (6:30923995 A>C,G), RS1004072472 (6:30923360 C>T), RS1004872003 (6:30916570 T>C), RS1004903354 (6:30916891 A>T), RS1005577614 (6:30919920 G>A,T), RS1005658139 (6:30912991 A>G), RS1005766564 (6:30920982 G>A,T), RS1006522742 (6:30922584 AGGTTTGCAG>A), RS1006661418 (6:30914317 C>T)

Disease associations

OMIM: gene MIM:612802 | disease phenotypes: MIM:615917, MIM:609060

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation defect type 20	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (3): combined oxidative phosphorylation defect type 20 (MONDO:0014397), mitochondrial disease (MONDO:0044970), hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (MONDO:0012191)

Orphanet (3): Combined oxidative phosphorylation defect type 20 (Orphanet:420728), Mitochondrial disease (Orphanet:68380), Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (Orphanet:137681)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563797	Combined Oxidative Phosphorylation Deficiency 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
bisphenol S	affects expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Coumestrol	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases methylation	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	decreases expression, increases abundance	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