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Aliases for RRM2 Gene

Aliases for RRM2 Gene

  • Ribonucleotide Reductase Regulatory Subunit M2 2 3 5
  • Ribonucleotide Reductase M2 Polypeptide 2 3
  • Ribonucleotide Reductase Small Subunit 3 4
  • Ribonucleotide Reductase Small Chain 3 4
  • EC 1.17.4.1 4 61
  • RR2 3 4
  • Ribonucleoside-Diphosphate Reductase Subunit M2 3
  • RR2M 3
  • R2 3

External Ids for RRM2 Gene

Previous GeneCards Identifiers for RRM2 Gene

  • GC02P010047
  • GC02P010314
  • GC02P010267
  • GC02P010284
  • GC02P010213
  • GC02P010262

Summaries for RRM2 Gene

Entrez Gene Summary for RRM2 Gene

  • This gene encodes one of two non-identical subunits for ribonucleotide reductase. This reductase catalyzes the formation of deoxyribonucleotides from ribonucleotides. Synthesis of the encoded protein (M2) is regulated in a cell-cycle dependent fashion. Transcription from this gene can initiate from alternative promoters, which results in two isoforms that differ in the lengths of their N-termini. Related pseudogenes have been identified on chromosomes 1 and X. [provided by RefSeq, Sep 2009]

CIViC summary for RRM2 Gene

GeneCards Summary for RRM2 Gene

RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) is a Protein Coding gene. Diseases associated with RRM2 include Pancreas Adenocarcinoma. Among its related pathways are superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis and Glutathione metabolism. GO annotations related to this gene include oxidoreductase activity and ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor. An important paralog of this gene is RRM2B.

UniProtKB/Swiss-Prot for RRM2 Gene

  • Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling.

Gene Wiki entry for RRM2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RRM2 Gene

Genomics for RRM2 Gene

Regulatory Elements for RRM2 Gene

Enhancers for RRM2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02G010119 1.8 FANTOM5 ENCODE dbSUPER 13.8 +0.1 107 6.1 CREB3L1 ZFP64 DMAP1 YY1 ZNF143 ZNF263 SP3 NFYC MEF2D ZNF610 RRM2 ENSG00000233502 CYS1 SNORA80B HPCAL1 LOC101929691 TAF1B ODC1 C2orf48
GH02G011103 0.8 ENCODE 5.1 +981.9 981866 2.0 ZFP64 ZNF121 ZNF316 GATA3 ARID3A FOS ETV6 RELB CREM MAFK RRM2 GC02P011102 FLJ33534
GH02G010143 0.7 ENCODE 5.2 +22.2 22203 1.3 CTCF NFIB NFRKB ZNF175 NFIC ZKSCAN8 ZNF584 CUX1 ZNF600 HNRNPL RRM2 C2orf48 ENSG00000206647 GC02M010155
GH02G010134 0.4 FANTOM5 3.7 +12.1 12112 0.3 POLR2A ENSG00000206647 RRM2 C2orf48 TAF1B
GH02G010125 1 Ensembl ENCODE 0.7 +4.0 4021 1.3 CTCF SMAD5 ZBED1 RAD21 FOSL1 ZNF121 JUND POLR2A HNF4A FOS SNORA80B LOC101929691 RRM2 C2orf48
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around RRM2 on UCSC Golden Path with GeneCards custom track

Promoters for RRM2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000112727 372 1801 HNRNPUL1 ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B CBX5 ZNF143
ENSR00000289709 1672 401 TBP JUND CEBPB FOS ZNF384 HNRNPL RBFOX2

Genomic Location for RRM2 Gene

Chromosome:
2
Start:
10,122,328 bp from pter
End:
10,131,419 bp from pter
Size:
9,092 bases
Orientation:
Plus strand

Genomic View for RRM2 Gene

Genes around RRM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RRM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RRM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RRM2 Gene

Proteins for RRM2 Gene

  • Protein details for RRM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P31350-RIR2_HUMAN
    Recommended name:
    Ribonucleoside-diphosphate reductase subunit M2
    Protein Accession:
    P31350
    Secondary Accessions:
    • B2R9B5
    • J3KP43
    • Q5WRU7

    Protein attributes for RRM2 Gene

    Size:
    389 amino acids
    Molecular mass:
    44878 Da
    Cofactor:
    Name=Fe cation; Xref=ChEBI:CHEBI:24875;
    Quaternary structure:
    • Heterodimer of a large and a small subunit.
    Miscellaneous:
    • Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2.
    SequenceCaution:
    • Sequence=DA477511; Type=Frameshift; Positions=87; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RRM2 Gene

    Alternative splice isoforms for RRM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RRM2 Gene

Selected DME Specific Peptides for RRM2 Gene

P31350:
  • VEGIFFSG
  • EARCFYGF
  • EYQRMGV
  • AEASFWTAEE
  • RFVIFPI
  • ALPVKLIGMNC
  • EEVDLSKD
  • KPSEERVREII
  • MPGLTFSNELI
  • GKTNFFEK
  • LFNAIET
  • LAFFAASDGIV
  • ENIHSEMYSLL
  • HSEMYSLLIDTY
  • YIEFVAD
  • KKADWALRWI
  • FAAVEGI
  • SNELISRDEGLH
  • NPFDFMENISL
  • MYKKAEASFWT
  • SDGIVNENL
  • AFAAVEG
  • HVLAFFA
  • FYGFQIA
  • FLTEALP

Post-translational modifications for RRM2 Gene

  • Phosphorylation on Ser-20 relieves the inhibitory effect on Wnt signaling.
  • Ubiquitination at Lys23, isoforms=261, Lys217, and Lys311
  • Modification sites at PhosphoSitePlus

Other Protein References for RRM2 Gene

Antibody Products

Domains & Families for RRM2 Gene

Suggested Antigen Peptide Sequences for RRM2 Gene

Graphical View of Domain Structure for InterPro Entry

P31350

UniProtKB/Swiss-Prot:

RIR2_HUMAN :
  • Belongs to the ribonucleoside diphosphate reductase small chain family.
Family:
  • Belongs to the ribonucleoside diphosphate reductase small chain family.
genes like me logo Genes that share domains with RRM2: view

No data available for Gene Families for RRM2 Gene

Function for RRM2 Gene

Molecular function for RRM2 Gene

GENATLAS Biochemistry:
ribonucleotide diphosphate reductase M2 polypeptide,pyrimidine biosynthetic pathway
UniProtKB/Swiss-Prot CatalyticActivity:
2-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin.
UniProtKB/Swiss-Prot Function:
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling.

Enzyme Numbers (IUBMB) for RRM2 Gene

Gene Ontology (GO) - Molecular Function for RRM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor NAS,IBA 1627826
GO:0005515 protein binding IPI 22632967
GO:0008199 ferric iron binding IEA --
GO:0016491 oxidoreductase activity IEA --
GO:0042803 protein homodimerization activity IEA --
genes like me logo Genes that share ontologies with RRM2: view
genes like me logo Genes that share phenotypes with RRM2: view

Animal Models for RRM2 Gene

MGI Knock Outs for RRM2:
  • Rrm2 tm1b(KOMP)Wtsi

Animal Model Products

miRNA for RRM2 Gene

miRTarBase miRNAs that target RRM2

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for RRM2

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RRM2 Gene

Localization for RRM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RRM2 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RRM2 gene
Compartment Confidence
nucleus 5
cytosol 5
peroxisome 2
mitochondrion 1
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for RRM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005971 ribonucleoside-diphosphate reductase complex IEA --
genes like me logo Genes that share ontologies with RRM2: view

Pathways & Interactions for RRM2 Gene

genes like me logo Genes that share pathways with RRM2: view

UniProtKB/Swiss-Prot P31350-RIR2_HUMAN

  • Pathway: Genetic information processing; DNA replication.

SIGNOR curated interactions for RRM2 Gene

Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for RRM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle TAS --
GO:0006260 DNA replication IEA --
GO:0009262 deoxyribonucleotide metabolic process IEA --
GO:0009263 deoxyribonucleotide biosynthetic process ISS,IBA --
GO:0015949 nucleobase-containing small molecule interconversion TAS --
genes like me logo Genes that share ontologies with RRM2: view

Drugs & Compounds for RRM2 Gene

(28) Drugs for RRM2 Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cladribine Approved, Investigational Pharma Target, inhibitor Apoptosis inducer in CLL cells 73
Gemcitabine Approved Pharma inhibitor, Biomarker Ribonucleotide reductase and DNA synthesis inhibitor, Nucleoside Analogs 2018
Hydroxyurea Approved Pharma inhibitor 223
Gallium nitrate Approved, Investigational Pharma Target, inhibitor 6
Clofarabine Approved, Investigational Pharma inhibitor, binder Antimetabolite,inhibit DNA polymerase and ribonucleotide reductase 159

(9) Additional Compounds for RRM2 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
dADP
  • 2'-Deoxyadenosine-5'-diphosphate
  • dADP
  • Deoxyadenosine diphosphate
2793-06-8
dcdp
  • 2'-Deoxy-Cytidine 5'-pyrophosphate
  • 2'-Deoxy-Cytidine pyrophosphate
  • 2'-Deoxycytidine 5'-diphosphate
  • 2'-Deoxycytidine diphosphate
  • 2'-Deoxycytidine-5'-diphosphate
800-73-7
dGDP
  • 2'-Deoxy-GDP
  • 2'-Deoxyguanosine-5'-diphosphate
  • 5'-dGDP
  • Deoxyguanosine 5'-diphosphate
  • Deoxyguanosine diphosphate
3493-09-2
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
15438-31-0

(5) ApexBio Compounds for RRM2 Gene

Compound Action Cas Number
Clofarabine Antimetabolite,inhibit DNA polymerase and ribonucleotide reductase 123318-82-1
Fludarabine Phosphate (Fludara) Inhibits STAT1 activation and DNA synthesis 75607-67-9
Gemcitabine 95058-81-4
Hydroxyurea 127-07-1
Triapine Ribonucleotide reductase inhibitor 236392-56-6
genes like me logo Genes that share compounds with RRM2: view

Transcripts for RRM2 Gene

Unigene Clusters for RRM2 Gene

Ribonucleotide reductase M2:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for RRM2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for RRM2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b · 3c ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10
SP1: - - -
SP2: - -
SP3: - -
SP4: -
SP5: - -

Relevant External Links for RRM2 Gene

GeneLoc Exon Structure for
RRM2
ECgene alternative splicing isoforms for
RRM2

Expression for RRM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RRM2 Gene

mRNA differential expression in normal tissues according to GTEx for RRM2 Gene

This gene is overexpressed in Esophagus - Mucosa (x4.6).

Protein differential expression in normal tissues from HIPED for RRM2 Gene

This gene is overexpressed in Ovary (53.3) and Breast (13.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for RRM2 Gene



Protein tissue co-expression partners for RRM2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of RRM2 Gene:

RRM2

SOURCE GeneReport for Unigene cluster for RRM2 Gene:

Hs.226390

Evidence on tissue expression from TISSUES for RRM2 Gene

  • Skin(4.8)
  • Nervous system(4.6)
  • Muscle(4.5)
  • Intestine(3.7)
  • Kidney(3.7)
  • Liver(3.5)
  • Blood(3.4)
  • Stomach(3.2)
  • Lung(2.5)
  • Heart(2.2)
  • Lymph node(2)
genes like me logo Genes that share expression patterns with RRM2: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for RRM2 Gene

Orthologs for RRM2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for RRM2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RRM2 34
  • 96.44 (n)
dog
(Canis familiaris)
Mammalia RRM2 34 35
  • 91.52 (n)
cow
(Bos Taurus)
Mammalia RRM2 34 35
  • 91.43 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 91 (a)
OneToMany
-- 35
  • 91 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia RRM2 35
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rrm2 34 16 35
  • 88.17 (n)
rat
(Rattus norvegicus)
Mammalia LOC100359539 34
  • 86.89 (n)
chicken
(Gallus gallus)
Aves RRM2 34 35
  • 79.67 (n)
lizard
(Anolis carolinensis)
Reptilia RRM2 35
  • 84 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rrm2.2 34
  • 77.75 (n)
African clawed frog
(Xenopus laevis)
Amphibia rrm2-prov 34
zebrafish
(Danio rerio)
Actinopterygii rrm2 34 35 35
  • 84 (a)
LOC100330864 34
  • 74.78 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.12256 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006818 34
  • 70.62 (n)
fruit fly
(Drosophila melanogaster)
Insecta RnrS 36 34 35
  • 70.52 (n)
worm
(Caenorhabditis elegans)
Secernentea rnr-2 36 34 35
  • 64.9 (n)
F19G12.2 36 35
  • 59 (a)
F58F9.1 35
  • 13 (a)
ManyToMany
Y57G11C.21 35
  • 9 (a)
ManyToMany
F54H12.2 35
  • 6 (a)
ManyToMany
K09F6.5 35
  • 5 (a)
ManyToMany
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AAL136C 34
  • 67.18 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RNR2 34 35 37
  • 64.39 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F15103g 34
  • 64.18 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons TSO2 34
  • 62.04 (n)
rice
(Oryza sativa)
Liliopsida Os06g0127900 34
  • 62.48 (n)
Os.9043 34
barley
(Hordeum vulgare)
Liliopsida Hv.2712 34
corn
(Zea mays)
Liliopsida Zm.5996 34
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2425 35
  • 70 (a)
OneToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU07887 34
  • 65.96 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes suc22 34
  • 64.69 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4812 34
Species where no ortholog for RRM2 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RRM2 Gene

ENSEMBL:
Gene Tree for RRM2 (if available)
TreeFam:
Gene Tree for RRM2 (if available)

Paralogs for RRM2 Gene

Paralogs for RRM2 Gene

(2) SIMAP similar genes for RRM2 Gene using alignment to 2 proteins:

Pseudogenes.org Pseudogenes for RRM2 Gene

genes like me logo Genes that share paralogs with RRM2: view

Variants for RRM2 Gene

Sequence variations from dbSNP and Humsavar for RRM2 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs1000349879 -- 10,120,711(+) GGGGG(C/T)AGGAG upstream-variant-2KB
rs1000548204 -- 10,131,664(+) AACCC(A/G)GGAGG downstream-variant-500B
rs1000931076 -- 10,124,201(+) CCTGG(A/G)TTCAA intron-variant
rs1001662393 -- 10,121,078(+) GCTTT(A/C)GTGTG upstream-variant-2KB
rs1001724121 -- 10,128,836(+) TGAAC(A/T)TTTTT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RRM2 Gene

Variant ID Type Subtype PubMed ID
dgv3715n100 CNV gain 25217958

Variation tolerance for RRM2 Gene

Residual Variation Intolerance Score: 27.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.69; 14.64% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RRM2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RRM2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RRM2 Gene

Disorders for RRM2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for RRM2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
pancreas adenocarcinoma
  • pancreatic adenocarcinoma
- elite association - COSMIC cancer census association via MalaCards
Search RRM2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for RRM2

Genetic Association Database (GAD)
RRM2
Human Genome Epidemiology (HuGE) Navigator
RRM2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RRM2
genes like me logo Genes that share disorders with RRM2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RRM2 Gene

Publications for RRM2 Gene

  1. Characterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses. (PMID: 11978970) Zhou B. … Yen Y. (Cytogenet. Cell Genet. 2001) 3 4 22 64
  2. Expression of nucleoside transporters, deoxycitidine kinase, ribonucleotide reductase regulatory subunits, and gemcitabine catabolic enzymes in primary ovarian cancer. (PMID: 19639316) Ferrandina G. … Del Tacca M. (Cancer Chemother. Pharmacol. 2010) 3 22 64
  3. Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase. (PMID: 20159953) Niida H. … Nakanishi M. (Genes Dev. 2010) 3 22 64
  4. Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection. (PMID: 20587610) Ucisik-Akkaya E. … Dorak M.T. (Mol. Hum. Reprod. 2010) 3 46 64
  5. Hepatitis B virus activates deoxynucleotide synthesis in nondividing hepatocytes by targeting the R2 gene. (PMID: 20155784) Cohen D. … Shaul Y. (Hepatology 2010) 3 22 64

Products for RRM2 Gene

Sources for RRM2 Gene

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