RRM2B

Summary

RRM2B (ribonucleotide reductase regulatory TP53 inducible subunit M2B, HGNC:17296) is a protein-coding gene on chromosome 8q22.3, encoding Ribonucleoside-diphosphate reductase subunit M2 B (Q7LG56). Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner.

This gene encodes the small subunit of a p53-inducible ribonucleotide reductase. This heterotetrameric enzyme catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. The product of this reaction is necessary for DNA synthesis. Mutations in this gene have been associated with autosomal recessive mitochondrial DNA depletion syndrome, autosomal dominant progressive external ophthalmoplegia-5, and mitochondrial neurogastrointestinal encephalopathy. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 50484 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial DNA depletion syndrome 8a (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 431 total — 17 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 189
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17296
Approved symbol	RRM2B
Name	ribonucleotide reductase regulatory TP53 inducible subunit M2B
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	p53R2
Ensembl gene	ENSG00000048392
Ensembl biotype	protein_coding
OMIM	604712
Entrez	50484

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000251810, ENST00000395910, ENST00000395912, ENST00000517517, ENST00000519125, ENST00000519317, ENST00000519962, ENST00000522368, ENST00000522394, ENST00000523957, ENST00000854932, ENST00000930763, ENST00000930764, ENST00000930765, ENST00000941786

RefSeq mRNA: 3 — MANE Select: NM_015713 NM_001172477, NM_001172478, NM_015713

CCDS: CCDS34932, CCDS55267

Canonical transcript exons

ENST00000251810 — 9 exons

Exon	Start	End
ENSE00000926193	102218814	102218947
ENSE00000926194	102224046	102224140
ENSE00001019056	102204502	102208285
ENSE00001161985	102238827	102238961
ENSE00001799324	102224885	102225018
ENSE00003465301	102212776	102212889
ENSE00003508149	102214054	102214158
ENSE00003547865	102232149	102232304
ENSE00003595771	102225918	102226034

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 96.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.3780 / max 361.4076, expressed in 1807 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94261	15.2822	1776
94259	2.7736	1149
94260	1.7893	1038
94262	1.5975	903
94257	1.3969	648
94258	0.9157	540
94256	0.6227	291

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.73	gold quality
oocyte	CL:0000023	95.51	gold quality
deltoid	UBERON:0001476	93.67	gold quality
islet of Langerhans	UBERON:0000006	93.33	gold quality
quadriceps femoris	UBERON:0001377	93.31	gold quality
vastus lateralis	UBERON:0001379	93.09	gold quality
germinal epithelium of ovary	UBERON:0001304	92.80	gold quality
tibialis anterior	UBERON:0001385	92.45	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.45	gold quality
palpebral conjunctiva	UBERON:0001812	92.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.97	gold quality
skeletal muscle tissue	UBERON:0001134	91.87	gold quality
calcaneal tendon	UBERON:0003701	91.85	gold quality
visceral pleura	UBERON:0002401	91.78	gold quality
substantia nigra pars compacta	UBERON:0001965	91.62	gold quality
epithelial cell of pancreas	CL:0000083	91.58	silver quality
lateral nuclear group of thalamus	UBERON:0002736	91.09	gold quality
skeletal muscle organ	UBERON:0014892	91.00	gold quality
muscle of leg	UBERON:0001383	90.63	gold quality
gastrocnemius	UBERON:0001388	90.63	gold quality
left ventricle myocardium	UBERON:0006566	90.62	gold quality
muscle tissue	UBERON:0002385	90.60	gold quality
heart right ventricle	UBERON:0002080	90.55	gold quality
biceps brachii	UBERON:0001507	89.46	gold quality
renal medulla	UBERON:0000362	89.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.31	gold quality
stromal cell of endometrium	CL:0002255	89.16	gold quality
myocardium	UBERON:0002349	89.14	silver quality
lateral globus pallidus	UBERON:0002476	89.03	gold quality
tibia	UBERON:0000979	88.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	724.29
E-ANND-3	yes	8.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, EGR1, GLI1, MTA1, NFKB1, POU2F1, TP53, TP73

miRNA regulators (miRDB)

176 targeting RRM2B, 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-4425	100.00	67.59	1049
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• p53R2-dependent DNA synthesis plays a pivotal role in cell survival by repairing damaged DNA (PMID:11719458)
• Expression of p53R2, newly p53 target in oral normal epithelium, epithelial dysplasia and squamous cell carcinoma. (PMID:12565178)
• Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits. (PMID:12615712)
• UV-induced activation of p53R2 transcription and binding of p53R2 to hRRM1 to form RR holoenzyme are impaired in the p53-mutant cell line PC3. (PMID:14583450)
• Four regulatory-region variants were found, of which three were single nucleotide polymorphisms (SNPs) (nt 1 789 C/G, nt 1 928 A/G, 1 933 T/C), and one was 20 bp insertion which replaced a ATTTT between nt 1831 and 1835. (PMID:16127747)
• we developed a p53R2-dependent luciferase reporter gene assay, and demonstrated dose-dependent luminescence caused by adriamycin in two human cell lines that express wild-type p53, MCF-7 and HepG2 (PMID:16236544)
• RRM2 and p53R2 subunits share the same binding site on RRM1 (PMID:16376858)
• Expressions of p53 and p53R2 proteins should be useful for determining the tumor properties, including prognosis, in patients with esophageal squamous cell carcinoma. (PMID:16778101)
• Catalytic properties are assessed. (PMID:16846634)
• ectopic expression of human papillomavirus 16 E6 impaired p53R2 induction after DNA damage in human fibroblasts (PMID:16872707)
• Mutation of RRM2B is associated with mitochondrial Diseases (PMID:17486094)
• p53R2 expression is reduced after X-ray irradiation following the transfection of p53R2 siRNAin esophageal squamous cell carcinoma. This could potentially improve efficacy of radiotheraepy. (PMID:17671702)
• a protective function of the p53R2 ribonucleotide reductase subunit in prevention or repair of NO-mediated genotoxic injury. (PMID:18474260)
• Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exons 6, 8, and 9, confirming that RRM2B mutations are important causes of MDS. (PMID:18504129)
• analysis of the effects of p53R2 silencing on DNA damage in LNCaP cells (PMID:18505925)
• p53R2 constitutes a potential target for anticancer drugs as well as a diagnostic marker in cancer. (PMID:18760875)
• The redox property, structure, and function of hRRM2 and p53R2, are studied. (PMID:19082948)
• This report describes two brothers, both deceased in infancy, with severe depletion of mitochondrial DNA (mtDNA) in muscle tissue. A novel missense mutation in the RRM2B gene, encoding the p53R2 subunit, was identified (PMID:19138848)
• A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. (PMID:19664747)
• This study expands the clinical spectrum of impaired RIR2B function. (PMID:19667227)
• The X-ray crystal structure of human p53R2 is determined to 2.6 A, in which monomers A and B exhibit mono- and binuclear iron occupancy, respectively. Sequence-structure-function correlations that differentiate p53R2 and RRM2 are revealed. (PMID:19728742)
• This study correlates the distinct catalytic mechanisms of the small subunits hp53R2 and hRRM2 with a hydrogen-bonding network. (PMID:20484015)
• p53R2 may suppress cancer cell proliferation; plays critical roles not only in DNA damage repair but also in proliferation of cancer cells (PMID:21216934)
• oss of p53R2 affects ribonucleotide reduction only in resting cells and leads to a decrease of dNTP catabolism by substrate cycles that counterweigh the loss of anabolic activity (PMID:21297166)
• Evidence that disease pathogenesis may be caused by defective RNR assembly is given. (PMID:21378381)
• Increased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. (PMID:21451941)
• this study provides functional evidence that mitochondria is one of p53R2-targeted organelles and suggests an unexpected function of p53R2, which is beyond known ribonucleotide reductase function on dNTP synthesis, in mitochondrial homeostatic control. (PMID:21640705)
• Adult-onset progressive external ophthalmoplegia due to RRM2B mutations is associated with a benign myopathic phenotype and characterized by muscle-restricted, mitochondrial DNA deletions. (PMID:21646632)
• p53R2 expression seems more important than that of hRRM2 in prognosis of early-stage lung cancer. (PMID:21965764)
• In nontransformed cells only during quiescence, protein p53R2 is required for maintenance of mitochondrial DNA and for optimal DNA repair after ultraviolet damage. (PMID:22847445)
• These results confirm a role for p53R2 in both Clofarabine and decitabine mechanism of action (PMID:22884950)
• p53R2 is directly regulated by p53 and also by a MEK2 (ERK kinase 2/MAP kinase kinase 2)-dependent pathway. (PMID:22895183)
• Propose p53R2 as a therapeutic target to enhance the effectiveness of chemotherapy in patients with p53R2-positive melanoma. (PMID:22902076)
• p53R2 could regulate matrix synthesis via Akt phosphorylation during chondrocyte mechanotransduction. Down-regulation of p53R2 may be a new therapeutic approach in OA therapy. (PMID:22954457)
• RRM2B is highly induced in a p53-dependent manner during senescence and is expressed at higher levels in senescent precancerous human prostatic intraepithelial neoplasm lesions compared to adjacent normal prostate glands. (PMID:23139867)
• RRM2B expression may discriminate cervical cancer phenotype and radiochemotherapy outcome (PMID:23552804)
• Ribonucleotide reductase M2B inhibits cell migration and spreading by early growth response protein 1-mediated phosphatase and tensin homolog/Akt1 pathway in hepatocellular carcinoma. (PMID:24214128)
• we found no support of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy. (PMID:24215511)
• in Turkish population p53R2 genotype distributions between head and neck squamous epithelial cell cancer patients and control groups were not statistically significantly different. (PMID:24861915)
• Data indicate that forkhead transcription factorsF OXO3 directly bound to and transcriptionally activated the promoter of ribonucleotide reductase subunit RRM2B, and induced the expression of RRM2B at RNA and protein levels. (PMID:24947616)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrm2b	ENSDARG00000033367
mus_musculus	Rrm2b	ENSMUSG00000022292
rattus_norvegicus	Rrm2b	ENSRNOG00000025454
drosophila_melanogaster	RnrS	FBGN0011704
caenorhabditis_elegans		WBGENE00004392

Paralogs (1): RRM2 (ENSG00000171848)

Protein

Protein identifiers

Ribonucleoside-diphosphate reductase subunit M2 B — Q7LG56 (reviewed: Q7LG56)

Alternative names: TP53-inducible ribonucleotide reductase M2 B, p53-inducible ribonucleotide reductase small subunit 2-like protein

All UniProt accessions (3): Q7LG56, E5RG52, H0YAV1

UniProt curated annotations — full annotation on UniProt →

Function. Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage.

Subunit / interactions. Heterotetramer with large (RRM1) subunit. Interacts with p53/TP53. Interacts with RRM1 in response to DNA damage.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed at a high level in skeletal muscle and at a weak level in thymus. Expressed in epithelial dysplasias and squamous cell carcinoma.

Disease relevance. Mitochondrial DNA depletion syndrome 8A (MTDPS8A) [MIM:612075] A disorder due to mitochondrial dysfunction characterized by various combinations of neonatal hypotonia, neurological deterioration, respiratory distress, lactic acidosis, and renal tubulopathy. The disease is caused by variants affecting the gene represented in this entry. Mitochondrial DNA depletion syndrome 8B (MTDPS8B) [MIM:612075] A disease due to mitochondrial dysfunction and characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy. The disease is caused by variants affecting the gene represented in this entry. Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 5 (PEOA5) [MIM:613077] A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. The disease is caused by variants affecting the gene represented in this entry. Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction (RCDFRD) [MIM:268315] An autosomal recessive disease characterized by visual impairment due to rod-cone dystrophy, sensorineural hearing loss, and Fanconi-type renal dysfunction resulting in rickets-like skeletal changes. Death may occur in childhood or young adulthood due to renal failure. Disease onset is before age 5 years. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 iron ions per subunit.

Induction. In response to DNA damage in a wild-type p53/TP53-dependent manner.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the ribonucleoside diphosphate reductase small chain family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q7LG56-1	1	yes
Q7LG56-2	2, Long form
Q7LG56-3	3, Short form gamma
Q7LG56-4	4, Short form beta
Q7LG56-5	5, Short form
Q7LG56-6	6

RefSeq proteins (3): NP_001165948, NP_001165949, NP_056528* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000358	RNR_small_fam	Family
IPR009078	Ferritin-like_SF	Homologous_superfamily
IPR012348	RNR-like	Homologous_superfamily
IPR030475	RNR_small_AS	Active_site
IPR033909	RNR_small	Family

Pfam: PF00268

Enzyme classification (BRENDA):

• EC 1.17.4.1 — ribonucleoside-diphosphate reductase (BRENDA: 56 organisms, 130 substrates, 474 inhibitors, 39 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CDP	0.0005–0.31	14
ADP	0.0078–0.3	6
GDP	0.0012–0.37	4
UDP	0.08–1.2	4
ATP	0.07	1
DATP	0.003	1
DTTP	0.0015	1
GLUTAREDOXIN	0.0001	1
GLUTAREDOXIN 1	0.006	1
THIOREDOXIN	0.003	1

Catalyzed reactions (Rhea), 1 shown:

• a 2’-deoxyribonucleoside 5’-diphosphate + [thioredoxin]-disulfide + H2O = a ribonucleoside 5’-diphosphate + [thioredoxin]-dithiol (RHEA:23252)

UniProt features (52 total): helix 18, sequence variant 13, binding site 7, splice variant 6, turn 2, strand 2, chain 1, region of interest 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4DJN	X-RAY DIFFRACTION	2.2
3HF1	X-RAY DIFFRACTION	2.6
2VUX	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7LG56-F1	85.73	0.76

Functional residue map

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

Catalytic / active sites (1): 138

Ligand- & substrate-binding residues (7): 100; 131; 131; 134; 194; 228; 231

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-499943	Interconversion of nucleotide di- and triphosphates
R-HSA-5628897	TP53 Regulates Metabolic Genes

MSigDB gene sets: 553 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_RESPONSE_TO_AMINE, GOBP_MITOCHONDRIAL_DNA_METABOLIC_PROCESS, GOLDRATH_IMMUNE_MEMORY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, KAUFFMANN_DNA_REPAIR_GENES, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (16): DNA synthesis involved in DNA repair (GO:0000731), kidney development (GO:0001822), renal system process (GO:0003014), mitochondrial DNA replication (GO:0006264), DNA repair (GO:0006281), response to oxidative stress (GO:0006979), ribonucleoside diphosphate metabolic process (GO:0009185), deoxyribonucleoside triphosphate metabolic process (GO:0009200), deoxyribonucleotide biosynthetic process (GO:0009263), 2’-deoxyribonucleotide biosynthetic process (GO:0009265), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), response to amine (GO:0014075), positive regulation of G0 to G1 transition (GO:0070318), negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902254), DNA damage response (GO:0006974), positive regulation of mitotic cell cycle phase transition (GO:1901992)

GO Molecular Function (5): ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor (GO:0004748), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (7): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), ribonucleoside-diphosphate reductase complex (GO:0005971), nucleus (GO:0005634), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of nucleotides	1
Transcriptional Regulation by TP53	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
2’-deoxyribonucleotide metabolic process	2
cytoplasm	2
intracellular membrane-bounded organelle	2
DNA repair	1
DNA biosynthetic process	1
animal organ development	1
renal system development	1
system process	1
mitochondrion	1
DNA-templated DNA replication	1
mitochondrial DNA metabolic process	1
DNA metabolic process	1
DNA damage response	1
response to stress	1
nucleoside diphosphate metabolic process	1
biosynthetic process	1
deoxyribonucleotide metabolic process	1
nucleotide biosynthetic process	1
deoxyribose phosphate biosynthetic process	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
response to nitrogen compound	1
G0 to G1 transition	1
regulation of G0 to G1 transition	1
positive regulation of cell cycle process	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
negative regulation of signal transduction by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
negative regulation of intrinsic apoptotic signaling pathway	1
cellular response to stress	1
mitotic cell cycle phase transition	1
positive regulation of mitotic cell cycle	1
positive regulation of cell cycle phase transition	1
regulation of mitotic cell cycle phase transition	1
ribonucleoside-diphosphate reductase activity	1
protein binding	1
cation binding	1

Protein interactions and networks

STRING

2294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRM2B	RRM1	P23921	996
RRM2B	POLG	P54098	942
RRM2B	POLG2	Q9UHN1	930
RRM2B	TP53	P04637	923
RRM2B	DGUOK	P78532	911
RRM2B	MPV17	P39210	901
RRM2B	SUCLA2	Q9P2R7	901
RRM2B	RRM2	P31350	893
RRM2B	TWNK	Q96RR1	880
RRM2B	SLC25A4	P12235	838
RRM2B	TYMP	P19971	798
RRM2B	SUCLG1	P53597	771
RRM2B	TK2	O00142	713
RRM2B	PYCR2	Q96C36	655
RRM2B	MDM2	Q00987	641

IntAct

46 interactions, top by confidence:

A	B	Type	Score
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
RRM2B	RRM2B	psi-mi:“MI:0915”(physical association)	0.670
RRM2	HSPA8	psi-mi:“MI:0914”(association)	0.640
ORC4	RRM2B	psi-mi:“MI:0915”(physical association)	0.600
RRM2B	ORC4	psi-mi:“MI:0915”(physical association)	0.600
RRM2B	RNF41	psi-mi:“MI:0915”(physical association)	0.560
RRM2	CDC27	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
RRM1	GLRX3	psi-mi:“MI:0914”(association)	0.530
GMFB	GMFG	psi-mi:“MI:0914”(association)	0.530
RRM2	RRM2B	psi-mi:“MI:0914”(association)	0.530
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
OPALIN	BTAF1	psi-mi:“MI:0914”(association)	0.530
RRM2B	ATM	psi-mi:“MI:0915”(physical association)	0.500
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
RRM2B	ATRIP	psi-mi:“MI:0915”(physical association)	0.400
MDM2	RRM2B	psi-mi:“MI:0915”(physical association)	0.400
RRM2B	TP53	psi-mi:“MI:0914”(association)	0.350
ATM	RRM1	psi-mi:“MI:0914”(association)	0.350
RRM2B	NBN	psi-mi:“MI:0914”(association)	0.350
EPHA1	MYO1B	psi-mi:“MI:0914”(association)	0.350
FGFR2	LANCL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (92): RRM2B (Two-hybrid), RRM2B (Two-hybrid), RRM2 (Affinity Capture-MS), INPPL1 (Affinity Capture-MS), RRM2B (Affinity Capture-MS), RRM2B (Biochemical Activity), RRM2B (Affinity Capture-MS), RRM2B (Affinity Capture-MS), RNF41 (Two-hybrid), RRM2 (Affinity Capture-MS), RRM2B (Affinity Capture-MS), INPPL1 (Affinity Capture-MS), RRM2B (Affinity Capture-MS), TPM2 (Affinity Capture-MS), RRM2B (Affinity Capture-MS)

ESM2 similar proteins: A6MZM2, G1SKZ8, G1TSG1, O48650, O60739, P35268, P41568, P42678, P47198, P47826, P48597, P50886, P50894, P53026, P53027, P55769, P55770, P56330, P61220, P62084, P62906, P62907, P67984, P67985, Q0D5W6, Q28IL6, Q3B8S0, Q4R4X9, Q4R5C6, Q4R5I3, Q4R5P3, Q4R741, Q5E9E6, Q5R9G0, Q5XH16, Q6P8E9, Q6PC69, Q6PEE3, Q7LG56, Q7ZYS8

Diamond homologs: A0A7H0DN21, O15910, O46310, O57175, P07201, P09938, P0C8I0, P0C8I1, P0C8I2, P0DKH2, P0DKH3, P0DSS7, P0DSS8, P11157, P11158, P20493, P26713, P28847, P29883, P31350, P32209, P36603, P42170, P42492, P42521, P48592, P49723, P49730, P50649, P50650, P50651, P79733, Q4KLN6, Q4R741, Q4R7Q7, Q5R9G0, Q60561, Q6PEE3, Q6R7K3, Q6UDJ1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	RRM2B	phosphorylation
“UV stress”	up-regulates	RRM2B
RRM2B	“up-regulates activity”	RRM1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G2/M Checkpoints	5	19.2×	3e-04
Regulation of TP53 Activity	5	19.0×	3e-04
Cell Cycle Checkpoints	7	17.7×	4e-05
G2/M DNA damage checkpoint	5	17.2×	3e-04
Regulation of TP53 Activity through Phosphorylation	5	16.8×	3e-04
Transcriptional Regulation by TP53	5	8.9×	3e-03
Cell Cycle	7	7.2×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein-containing complex assembly	5	11.9×	5e-03
DNA repair	6	8.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	21
Uncertain significance	175
Likely benign	101
Benign	47

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1201518	NM_015713.5(RRM2B):c.550+1G>A	Pathogenic
215092	NM_015713.5(RRM2B):c.599G>A (p.Gly200Glu)	Pathogenic
215099	NM_015713.5(RRM2B):c.205-2A>G	Pathogenic
2709678	NM_015713.5(RRM2B):c.504del (p.Ala169fs)	Pathogenic
2966802	NM_015713.5(RRM2B):c.158G>A (p.Trp53Ter)	Pathogenic
30432	NM_015713.5(RRM2B):c.950del (p.Ser316_Leu317insTer)	Pathogenic
30433	NM_015713.5(RRM2B):c.965dup (p.Asn322fs)	Pathogenic
3614432	NM_015713.5(RRM2B):c.432_435del (p.Tyr145fs)	Pathogenic
3653141	NM_015713.5(RRM2B):c.439A>T (p.Arg147Ter)	Pathogenic
4845340	NM_015713.5(RRM2B):c.414_415del (p.Tyr138_Ser139delinsTer)	Pathogenic
5386	NM_015713.5(RRM2B):c.850C>T (p.Gln284Ter)	Pathogenic
5387	NM_015713.5(RRM2B):c.322-2A>G	Pathogenic
5388	NM_015713.5(RRM2B):c.580G>A (p.Glu194Lys)	Pathogenic
5390	NM_015713.5(RRM2B):c.707G>T (p.Cys236Phe)	Pathogenic
5391	NM_015713.5(RRM2B):c.979C>T (p.Arg327Ter)	Pathogenic
5394	NM_015713.5(RRM2B):c.362G>A (p.Arg121His)	Pathogenic
830053	NM_015713.5(RRM2B):c.527_528insG (p.Ile176fs)	Pathogenic
1030272	NM_015713.5(RRM2B):c.48+268_48+269delinsAA	Likely pathogenic
132112	NM_015713.5(RRM2B):c.328C>T (p.Arg110Cys)	Likely pathogenic
132123	NM_015713.5(RRM2B):c.846G>C (p.Met282Ile)	Likely pathogenic
1524868	NM_015713.5(RRM2B):c.455+1G>A	Likely pathogenic
215100	NM_015713.5(RRM2B):c.208G>T (p.Asp70Tyr)	Likely pathogenic
216993	NM_015713.5(RRM2B):c.635_636insAAG (p.Gly212_Leu213insSer)	Likely pathogenic
2687854	NM_015713.5(RRM2B):c.184T>N (p.Ser62Xaa)	Likely pathogenic
2719924	NM_015713.5(RRM2B):c.684+1G>A	Likely pathogenic
2834623	NM_015713.5(RRM2B):c.205-1G>C	Likely pathogenic
3062047	NM_015713.5(RRM2B):c.472G>A (p.Ala158Thr)	Likely pathogenic
3064800	NM_015713.5(RRM2B):c.94G>T (p.Glu32Ter)	Likely pathogenic
3068322	NM_015713.5(RRM2B):c.49-2A>G	Likely pathogenic
3250467	NM_015713.5(RRM2B):c.540del (p.Lys180fs)	Likely pathogenic

SpliceAI

1139 predictions. Top by Δscore:

Variant	Effect	Δscore
8:102208146:T:TA	donor_gain	1.0000
8:102208164:T:C	donor_gain	1.0000
8:102212770:CATTA:C	donor_loss	1.0000
8:102212771:ATTAC:A	donor_loss	1.0000
8:102212772:TTACC:T	donor_loss	1.0000
8:102212773:TA:T	donor_loss	1.0000
8:102212774:ACCTT:A	donor_loss	1.0000
8:102212885:AACTC:A	acceptor_gain	1.0000
8:102212887:CTC:C	acceptor_gain	1.0000
8:102212888:TCCT:T	acceptor_loss	1.0000
8:102212889:CCTGG:C	acceptor_loss	1.0000
8:102212890:C:CA	acceptor_loss	1.0000
8:102212895:A:AC	acceptor_gain	1.0000
8:102212902:C:CT	acceptor_gain	1.0000
8:102212903:A:T	acceptor_gain	1.0000
8:102214043:T:TA	donor_gain	1.0000
8:102214044:C:A	donor_gain	1.0000
8:102218812:A:AC	donor_gain	1.0000
8:102218813:C:CC	donor_gain	1.0000
8:102224044:A:AC	donor_gain	1.0000
8:102224045:C:CC	donor_gain	1.0000
8:102224139:CC:C	acceptor_gain	1.0000
8:102224140:CC:C	acceptor_gain	1.0000
8:102224880:AATAC:A	donor_loss	1.0000
8:102224881:ATAC:A	donor_loss	1.0000
8:102224882:TACC:T	donor_loss	1.0000
8:102224883:ACC:A	donor_loss	1.0000
8:102225015:CCAC:C	acceptor_gain	1.0000
8:102225016:CAC:C	acceptor_gain	1.0000
8:102225016:CACC:C	acceptor_gain	1.0000

AlphaMissense

2342 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:102218892:A:C	F202L	0.999
8:102218892:A:T	F202L	0.999
8:102218894:A:G	F202L	0.999
8:102232163:A:G	W64R	0.999
8:102232163:A:T	W64R	0.999
8:102218814:T:A	E228D	0.998
8:102218814:T:G	E228D	0.998
8:102218904:G:C	F198L	0.998
8:102218904:G:T	F198L	0.998
8:102218906:A:G	F198L	0.998
8:102224940:G:C	H134D	0.998
8:102208198:A:G	Y331H	0.997
8:102208217:A:C	F324L	0.997
8:102208217:A:T	F324L	0.997
8:102208219:A:G	F324L	0.997
8:102208220:G:C	F323L	0.997
8:102208220:G:T	F323L	0.997
8:102208222:A:G	F323L	0.997
8:102214152:G:C	H231D	0.997
8:102218818:T:A	D227V	0.997
8:102218818:T:G	D227A	0.997
8:102218819:C:G	D227H	0.997
8:102218926:G:T	A191D	0.997
8:102224947:C:A	E131D	0.997
8:102224947:C:G	E131D	0.997
8:102224948:T:A	E131V	0.997
8:102225921:A:C	N106K	0.997
8:102225921:A:T	N106K	0.997
8:102232161:C:A	W64C	0.997
8:102232161:C:G	W64C	0.997

dbSNP variants (sampled 300 via entrez): RS1000042495 (8:102239407 G>A,T), RS1000056293 (8:102233266 T>C,G), RS1000258970 (8:102208993 T>G), RS1000311198 (8:102208626 T>C,G), RS1000352405 (8:102219618 G>T), RS1000384955 (8:102219237 C>A,G), RS1000568235 (8:102221976 G>A), RS1000634609 (8:102226345 A>T), RS1000730872 (8:102228480 C>T), RS1000919508 (8:102215023 T>A,C,G), RS1000992716 (8:102213163 G>A), RS1001065537 (8:102206612 T>G), RS1001183151 (8:102228207 G>A), RS1001205975 (8:102239367 T>C), RS1001277887 (8:102213438 T>C)

Disease associations

OMIM: gene MIM:604712 | disease phenotypes: MIM:612075, MIM:268315, MIM:613077

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial DNA depletion syndrome 8a	Definitive	Autosomal recessive
progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5	Strong	Autosomal dominant
autosomal dominant progressive external ophthalmoplegia	Supportive	Autosomal dominant
mitochondrial neurogastrointestinal encephalomyopathy	Supportive	Autosomal recessive
adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy	Supportive	Autosomal dominant
Kearns-Sayre syndrome	Supportive	Autosomal recessive

Mondo (12): mitochondrial DNA depletion syndrome 8a (MONDO:0012792), rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction (MONDO:0010000), progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 (MONDO:0013117), idiopathic camptocormia (MONDO:0015271), mitochondrial disease (MONDO:0044970), progressive external ophthalmoplegia (MONDO:0005181), sensorineural hearing loss disorder (MONDO:0020678), adult Fanconi syndrome (MONDO:0060778), autosomal dominant progressive external ophthalmoplegia (MONDO:0008003), mitochondrial neurogastrointestinal encephalomyopathy (MONDO:0017575), adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy (MONDO:0018002), Kearns-Sayre syndrome (MONDO:0010787)

Orphanet (4): Mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy (Orphanet:255235), Idiopathic camptocormia (Orphanet:1320), Mitochondrial disease (Orphanet:68380), Progressive external ophthalmoplegia (Orphanet:520820)

HPO phenotypes

189 total (30 of 189 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000017	Nocturia
HP:0000044	Hypogonadotropic hypogonadism
HP:0000114	Proximal tubulopathy
HP:0000218	High palate
HP:0000338	Hypomimic face
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000496	Abnormality of eye movement
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000543	Optic disc pallor
HP:0000544	External ophthalmoplegia
HP:0000565	Esotropia
HP:0000580	Pigmentary retinopathy
HP:0000590	Progressive external ophthalmoplegia
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000648	Optic atrophy
HP:0000716	Depression
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000815	Hypergonadotropic hypogonadism
HP:0000819	Diabetes mellitus

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004147_19	Chronic obstructive pulmonary disease	4.000000e-06
GCST005993_57	Mean corpuscular hemoglobin	3.000000e-10
GCST006011_27	Mean corpuscular volume	3.000000e-15
GCST006585_1724	Blood protein levels	1.000000e-10
GCST006585_2401	Blood protein levels	7.000000e-31
GCST008940_2	Chromosomal aberration frequency (total)	1.000000e-06
GCST90002403_636	Red blood cell count	3.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0009860	chromosomal aberration frequency
EFO:0004305	erythrocyte count

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D007625	Kearns-Sayre Syndrome	C05.651.460.700.500; C10.292.562.750.250.500; C10.597.622.447.511.500; C10.668.491.500.700.500; C11.590.472.250.500; C11.768.585.658.500.627; C14.280.238.510; C18.452.660.560.700.500; C23.550.291.500.688.500; C23.888.592.636.447.511.500
D017246	Ophthalmoplegia, Chronic Progressive External	C05.651.460.700; C10.292.562.750.250; C10.597.622.447.511; C10.668.491.500.700; C11.590.472.250; C18.452.660.560.700; C23.550.291.500.688; C23.888.592.636.447.511
C537968	Camptocormia (supp.)
C567768	Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Dominant, 5 (supp.)
C563575	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 1 (supp.)
C564829	Rod-Cone Dystrophy, Sensorineural Deafness, and Fanconi-Type Renal Dysfunction (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095215 (PROTEIN COMPLEX GROUP), CHEMBL3301398 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,524 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL231616	TRIAPINE	3	4,524

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1265138	Efficacy	3	cladribine;cytarabine	Leukemia;Myeloid;Acute

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1265138	RRM2B	3	1.75	1	cladribine;cytarabine
rs2607659	RRM2B		0.00	0
rs16918482	RRM2B		0.00	0
rs2607658	RRM2B		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.17.4.1 Ribonucleoside-diphosphate reductases

ChEMBL bioactivities

346 potent at pChembl≥5 of 385 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CHEMBL336289
9.15	IC50	0.7	nM	CHEMBL96993
9.00	IC50	1	nM	CHEMBL98729
8.70	IC50	2	nM	CHEMBL1169533
8.52	IC50	3	nM	CHEMBL133754
8.52	IC50	3	nM	CHEMBL305199
8.40	IC50	4	nM	CHEMBL95998
8.30	IC50	5	nM	CHEMBL95766
8.30	IC50	5	nM	CHEMBL335164
8.22	IC50	6	nM	CHEMBL134961
8.19	IC50	6.4	nM	CHEMBL120710
8.15	IC50	7	nM	CHEMBL133827
8.15	IC50	7	nM	CHEMBL37210
8.12	IC50	7.5	nM	CHEMBL431851
7.82	IC50	15	nM	CHEMBL71945
7.75	IC50	18	nM	CHEMBL443029
7.70	IC50	20	nM	CHEMBL6001460
7.70	IC50	20	nM	CHEMBL1169532
7.66	IC50	22	nM	CHEMBL96993
7.66	IC50	22	nM	CHEMBL439791
7.66	IC50	22	nM	CHEMBL120060
7.62	IC50	24	nM	CHEMBL305229
7.57	IC50	27	nM	CHEMBL131682
7.52	IC50	30	nM	CHEMBL5941178
7.52	IC50	30	nM	CHEMBL5913113
7.47	IC50	34	nM	CHEMBL414818
7.44	IC50	36	nM	CHEMBL118524
7.43	IC50	37	nM	CHEMBL98729
7.40	IC50	40	nM	CHEMBL5958580
7.40	IC50	40	nM	CHEMBL5777432
7.40	IC50	40	nM	CHEMBL132130
7.37	IC50	43	nM	CHEMBL99950
7.30	IC50	50	nM	CHEMBL5813221
7.30	IC50	50	nM	CHEMBL5797621
7.30	IC50	50	nM	CHEMBL6028518
7.30	IC50	50	nM	CHEMBL5987707
7.26	IC50	55	nM	CHEMBL1169533
7.22	IC50	60	nM	CHEMBL5775741
7.22	IC50	60	nM	CHEMBL5869217
7.22	IC50	60	nM	CHEMBL5844268
7.22	IC50	60	nM	CHEMBL5793033
7.22	IC50	60	nM	CHEMBL5960405
7.22	IC50	60	nM	CHEMBL5824595
7.22	IC50	60	nM	CHEMBL5935086
7.22	IC50	60	nM	CHEMBL6057994
7.22	IC50	60	nM	CHEMBL5813221
7.22	IC50	60	nM	CHEMBL5988394
7.22	IC50	60	nM	CHEMBL6019064
7.22	IC50	60	nM	CHEMBL6058380
7.22	IC50	60	nM	CHEMBL5857144

PubChem BioAssay actives

52 with measured affinity, of 369 total; 46 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4,4-dimethylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0006	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0007	uM
1-[(1S)-2-[[(1S)-1-carboxy-3-methylbutyl]amino]-1-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-oxoethyl]cyclopentane-1-carboxylic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0010	uM
(2R)-2-[[(2R)-3-carboxy-2-[[(2S)-2-[[(2R)-2-[[(2R,6S)-2,6-dimethylcyclohexyl]carbamoylamino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0020	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0030	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-5,5-dimethyl-4-oxohexanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0030	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0040	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4,4-dimethylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0050	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-4-oxo-5-(pentan-3-ylcarbamoylamino)heptanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0050	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-[[(2S)-1-hydroxy-4,4-dimethylpentan-2-yl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0060	uM
1-[(1S)-2-[[(1S)-1-carboxy-3-methylbutyl]amino]-1-[[(2S)-2-[[(2S)-2-(2-ethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-oxoethyl]cyclopent-3-ene-1-carboxylic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0064	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-(heptan-4-ylcarbamoylamino)-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0070	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S,5S)-6,6-dimethyl-4-oxo-2-(2-oxo-2-pyrrolidin-1-ylethyl)-5-(pentan-3-ylcarbamoylamino)heptanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0070	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-[methyl(3-phenylpropanoyl)amino]butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0075	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0150	uM
(3S)-4-[[(3R)-2,2-dimethylpentan-3-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0180	uM
(2R)-2-[[(2R)-3-carboxy-2-[[(2S)-2-[[(2R)-2-[[(2S,6S)-2,6-dimethylcyclohexyl]carbamoylamino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid;(2R)-2-[[(2R)-3-carboxy-2-[[(2S)-2-[[(2R)-2-[[(2R,6R)-2,6-dimethylcyclohexyl]carbamoylamino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0200	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0220	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-cyclohexyl-2-(3-phenylpropanoylamino)acetyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0220	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0240	uM
(3S)-4-[[(2R)-3,3-dimethylbutan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0270	uM
(3S)-4-[[(2S)-1-hydroxy-4,4-dimethylpentan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0340	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(3-phenylpropanoylamino)butanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0360	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-(2,2-dimethylpropylamino)-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0400	uM
(3S)-4-[[(1S)-1-carboxy-3-methylbutyl]amino]-3-[[(2S)-2-[[(2S)-2-(2-ethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2,2-dimethyl-4-oxobutanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0430	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-(3-phenylpropanoylamino)pentanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0610	uM
(3S)-4-(3,3-dimethylbutylamino)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.1000	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.1800	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.3400	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-(3-methylbutylamino)-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.3500	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-(propan-2-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.4400	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-(cyclohexylcarbamoylamino)-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.5000	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-(2-ethylbutanoylamino)-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.8600	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-[[(2R)-2-methyl-3-phenylpropanoyl]amino]butanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.8600	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.8800	uM
(3S)-3-[[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]-2-phenylacetyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-cyclohexylpropanoyl]amino]-4-[[(1S)-1-carboxy-2-phenylethyl]amino]-4-oxobutanoic acid	242343: Inhibition of mammalian ribonucleotide reductase in a standard dTTP-dependent GDP reductase assay	ic50	1.9000	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-(2-methylpropylamino)-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	1.9000	uM
(3S)-4-[[(3S)-2,2-dimethylpentan-3-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	2.0000	uM
(4S)-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxopropan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[3-(9H-fluoren-9-ylmethoxy)-3-oxo-2-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoic acid	242343: Inhibition of mammalian ribonucleotide reductase in a standard dTTP-dependent GDP reductase assay	ic50	2.4000	uM
(3S)-3-[[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[3-(9H-fluoren-9-ylmethoxy)-3-oxo-2-phenylpropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-cyclohexylpropanoyl]amino]-4-[[(1S)-1-carboxy-2-phenylethyl]amino]-4-oxobutanoic acid	242343: Inhibition of mammalian ribonucleotide reductase in a standard dTTP-dependent GDP reductase assay	ic50	2.4000	uM
(3S)-4-[[(2S)-3,3-dimethylbutan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	2.7000	uM
1-[(1S)-1-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)-methylamino]-3-methylbutanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-[[(2S)-1-hydroxy-4,4-dimethylpentan-2-yl]amino]-2-oxoethyl]cyclopentane-1-carboxylic acid	41530: Inhibitory activity against HSV-1 in baby hamster kidney cell	ec50	3.1000	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	4.0000	uM
1-[(1S)-1-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-[[(2S)-1-hydroxy-4,4-dimethylpentan-2-yl]amino]-2-oxoethyl]cyclopentane-1-carboxylic acid	41531: Inhibitory activity against HSV-2 in baby hamster kidney cell	ec50	6.5000	uM
1-[(1S)-1-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)-methylamino]-3-methylbutanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-[[(2S)-1-hydroxy-4-methylpentan-2-yl]amino]-2-oxoethyl]cyclopentane-1-carboxylic acid	41530: Inhibitory activity against HSV-1 in baby hamster kidney cell	ec50	7.3000	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-2-(3-phenylpropanoylamino)propanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	8.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects cotreatment, increases expression	9
Cisplatin	affects cotreatment, increases expression, decreases expression, affects reaction	7
sodium arsenite	affects expression, decreases expression, increases expression	6
Aflatoxin B1	increases expression, affects expression	6
Doxorubicin	affects expression, affects binding, decreases reaction, increases reaction, increases expression (+1 more)	5
Fluorouracil	increases expression, decreases response to substance, affects reaction	4
Resveratrol	affects cotreatment, increases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	increases abundance, decreases expression, affects cotreatment, affects expression	2
Methyl Methanesulfonate	increases expression	2
Methylnitronitrosoguanidine	increases expression, increases reaction, affects expression, affects localization, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tunicamycin	increases expression	2
Valproic Acid	increases expression, affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cyclosporine	increases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
ginger extract	increases abundance, affects cotreatment, affects expression	1
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
chloroacetaldehyde	affects expression	1
methylmercuric chloride	increases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
benzo(b)fluoranthene	affects cotreatment, increases expression	1

ChEMBL screening assays

47 unique, capped per target: 44 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1775985	Binding	Inhibition of human recombinant ribonucleotide reductase M2/M1 expressed in Escherichia coli BL21 (DE3) after 30 mins by [3H]CDP reduction method	Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3’-C-methyl-ribonucleosides as antitumor agents. — Eur J Med Chem
CHEMBL652605	Functional	Inhibitory activity against HSV-1 in baby hamster kidney cell	Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: a new class of antiviral agents. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1E3	Abcam HCT 116 RRM2B KO	Cancer cell line	Male
CVCL_B2EA	Abcam HeLa RRM2B KO	Cancer cell line	Female
CVCL_TJ77	HAP1 RRM2B (-) 1	Cancer cell line	Male
CVCL_TJ78	HAP1 RRM2B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

201 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
NCT01655212	PHASE3	TERMINATED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial
NCT02005822	PHASE3	COMPLETED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
NCT03374514	PHASE3	UNKNOWN	Cochlear Electrical Impedance and the Effect of Topical Dexamethasone on Cochlear Implant Surgery
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
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
NCT02497690	PHASE2	COMPLETED	Effectiveness of Therapy Via Telemedicine Following Cochlear Implants
NCT03107871	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
NCT04120116	PHASE2	COMPLETED	FX-322 in Adults With Stable Sensorineural Hearing Loss
NCT05061758	PHASE2	WITHDRAWN	A Trial of LY3056480 in Patients With SNLH
NCT07364747	PHASE2	RECRUITING	Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial
NCT02427178	PHASE1	WITHDRAWN	MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study
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