Cancer Cell Metabolism Database ~~ Bioinformatics and Systems Medicine Laboratory ~~

Cancer Cell Metabolism Gene Database

Cancer Cell Metabolism Gene DB

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	Gene Summary
	Phenotypic Information (metabolism pathway, cancer, disease, phenome)
	Mutations : SVs, CNVs, SNVs
	Gene expression: GE, Protein, DEGE, CNV vs GE
	Gene-Gene Network Information: Co-Expression Network, Interacting Genes & KEGG
	Pharmacological Information: Drug-Gene Network
	Cross referenced IDs

Gene Summary for RRM2

Basic gene info.	Gene symbol	RRM2
	Gene name	ribonucleotide reductase M2
	Synonyms	R2\|RR2\|RR2M
	Cytomap	UCSC genome browser: 2p25-p24
	Genomic location	chr2 :10262862-10271546
	Type of gene	protein-coding
	RefGenes	NM_001034.3, NM_001165931.1,
	Ensembl id	ENSG00000171848
	Description	ribonucleoside-diphosphate reductase subunit M2ribonucleotide reductase M2 polypeptideribonucleotide reductase small chainribonucleotide reductase small subunit
	Modification date	20141222
dbXrefs	MIM : 180390
	HGNC : HGNC
	Ensembl : ENSG00000171848
	HPRD : 01587
	Vega : OTTHUMG00000090449
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_RRM2
	BioGPS: 6241
	Gene Expression Atlas: ENSG00000171848
	The Human Protein Atlas: ENSG00000171848
Pathway	NCI Pathway Interaction Database: RRM2
	KEGG: RRM2
	REACTOME: RRM2
	ConsensusPathDB
	Pathway Commons: RRM2
Metabolism	MetaCyc: RRM2
	HUMANCyc: RRM2
Regulation	Ensembl's Regulation: ENSG00000171848
	miRBase: chr2 :10,262,862-10,271,546
	TargetScan: NM_001034
	cisRED: ENSG00000171848
Context	iHOP: RRM2
	cancer metabolism search in PubMed: RRM2
	UCL Cancer Institute: RRM2
Assigned class in ccmGDB	C

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Phenotypic Information for RRM2(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: RRM2
	Familial Cancer Database: RRM2

* This gene is included in those cancer gene databases.


Oncogene ¹	Tumor Suppressor gene ²	Cancer Gene Census ³	CancerGenes ⁴	Network of Cancer Gene ⁵	Significant driver gene in	Therapeutic Vulnerabilities in Cancer¹

cf) number; DB name
1 Oncogene; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
2 Tumor Suppressor gene; https://bioinfo.uth.edu/TSGene/,
3 Cancer Gene Census; http://www.nature.com/nrc/journal/v4/n3/abs/nrc1299.html,
4 CancerGenes; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
5 Network of Cancer Gene; http://ncg.kcl.ac.uk/index.php,
1Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
KEGG_PURINE_METABOLISM KEGG_PYRIMIDINE_METABOLISM KEGG_GLUTATHIONE_METABOLISM REACTOME_METABOLISM_OF_NUCLEOTIDES

Others
OMIM
Orphanet
Disease	KEGG Disease: RRM2
	MedGen: RRM2 (Human Medical Genetics with Condition)
	ClinVar: RRM2
Phenotype	MGI: RRM2 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: RRM2

Mutations for RRM2

* Under tables are showing count per each tissue to give us broad intuition about tissue specific mutation patterns.You can go to the detailed page for each mutation database's web site.

Structural Variants in COSMIC : go to COSMIC mutation histogram

There's no structural variation information in COSMIC data for this gene.

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows RRM2 related fusion information.

ID	Head Gene						Tail Gene
Accession	Gene_a	qStart_a	qEnd_a	Chromosome_a	tStart_a	tEnd_a	Gene_a	qStart_a	qEnd_a	Chromosome_a	tStart_a	tEnd_a
BQ379268	ADD1	36	92	4	2931732	2931788	RRM2	81	300	2	10263875	10264958
DB124334	CDH3	1	437	16	68678846	68679282	RRM2	434	555	2	10263171	10263621
AA826373	RRM2	1	389	2	10271152	10271540	NCKAP1	384	515	2	183866687	183866901

Other DBs for Structural Variants

Structural Variants in Ensembl: go to Ensembl Structural variation

Structural Variants in dbVar: go to dbVar

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Copy Number Variations in COSMIC : go to COSMIC mutation CNV/Expr

There's no copy number variation information in COSMIC data for this gene.

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SNV Counts per Each Loci in COSMIC data : go to COSMIC point mutation

: Non-synonymous mutation, : Synonymous mutation, Circle size denotes number of samples.
Maximum mutation count=2

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=24)	Stat. for Synonymous SNVs (# total SNVs=7)

Stat. for Deletions (# total SNVs=2)	Stat. for Insertions (# total SNVs=0)
	There's no inserted snv.

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Top 10 SNVs Having the Most Samples in COSMIC data

* When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site,primary_histology,mutation(aa),pubmedID.

GRCh37 position	Mutation(aa)	Unique sampleID count
chr2:10269209-10269209	p.M315I	2
chr2:10262969-10262969	p.Q15R	2
chr2:10263526-10263526	p.A63S	1
chr2:10269168-10269168	p.E302K	1
chr2:10263631-10263631	p.E98Q	1
chr2:10269488-10269488	p.S382Y	1
chr2:10264939-10264941	p.L179delL	1
chr2:10263530-10263530	p.G66fs*8	1
chr2:10263864-10263864	p.V107A	1
chr2:10264949-10264949	p.D181H	1

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SNV Counts per Each Loci in TCGA data

: non-synonymous mutation, : synonymous mutation, Circle size denotes number of samples.
maximum mutation count=1

Point Mutation/ Tissue ID	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20
# sample	3	2	1	4	1				1			5	1				2	3		7
# mutation	3	2	1	4	1				1			6	1				2	3		7
nonsynonymous SNV	2	1		4	1				1			5	1				1	3		7
synonymous SNV	1	1	1									1					1

cf) Tissue ID; Tissue type (1; BLCA[Bladder Urothelial Carcinoma], 2; BRCA[Breast invasive carcinoma], 3; CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], 4; COAD[Colon adenocarcinoma], 5; GBM[Glioblastoma multiforme], 6; Glioma Low Grade, 7; HNSC[Head and Neck squamous cell carcinoma], 8; KICH[Kidney Chromophobe], 9; KIRC[Kidney renal clear cell carcinoma], 10; KIRP[Kidney renal papillary cell carcinoma], 11; LAML[Acute Myeloid Leukemia], 12; LUAD[Lung adenocarcinoma], 13; LUSC[Lung squamous cell carcinoma], 14; OV[Ovarian serous cystadenocarcinoma ], 15; PAAD[Pancreatic adenocarcinoma], 16; PRAD[Prostate adenocarcinoma], 17; SKCM[Skin Cutaneous Melanoma], 18:STAD[Stomach adenocarcinoma], 19:THCA[Thyroid carcinoma], 20:UCEC[Uterine Corpus Endometrial Carcinoma])

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Top 10 SNVs Having the Most Samples in TCGA data

* We represented just top 10 SNVs. When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site, primary_histology, mutation(aa), pubmedID.

Genomic Position	Mutation(aa)	Unique sampleID count
chr2:10263127	p.D89G,RRM2	1
chr2:10264910	p.M315I,RRM2	1
chr2:10269234	p.V107A,RRM2	1
chr2:10263530	p.T318A,RRM2	1
chr2:10267090	p.S118S,RRM2	1
chr2:10269260	p.I324V,RRM2	1
chr2:10263558	p.M332I,RRM2	1
chr2:10267220	p.E122K,RRM2	1
chr2:10269373	p.E344Q,RRM2	1
chr2:10263601	p.F133V,RRM2	1

Other DBs for Point Mutations

Point Mutation Table of Ensembl: go to Ensembl variation table

Mutation of cBioPortal: go to cBioPortal's Cross-cancer alteration summary

Copy Number for RRM2 in TCGA

* Copy number data were extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered on Jan-05-2015. Function ProcessCNAData in TCGA-Assembler package was used to obtain gene-level copy number value which is calculated as the average copy number of the genomic region of a gene.

cf) Tissue ID[Tissue type]: BLCA[Bladder Urothelial Carcinoma], BRCA[Breast invasive carcinoma], CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], COAD[Colon adenocarcinoma], GBM[Glioblastoma multiforme], Glioma Low Grade, HNSC[Head and Neck squamous cell carcinoma], KICH[Kidney Chromophobe], KIRC[Kidney renal clear cell carcinoma], KIRP[Kidney renal papillary cell carcinoma], LAML[Acute Myeloid Leukemia], LUAD[Lung adenocarcinoma], LUSC[Lung squamous cell carcinoma], OV[Ovarian serous cystadenocarcinoma ], PAAD[Pancreatic adenocarcinoma], PRAD[Prostate adenocarcinoma], SKCM[Skin Cutaneous Melanoma], STAD[Stomach adenocarcinoma], THCA[Thyroid carcinoma], UCEC[Uterine Corpus Endometrial Carcinoma]

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Gene Expression for RRM2

Gene Expression in Cancer Cell-lines (CCLE)

* CCLE gene expression data were extracted from CCLE_Expression_Entrez_2012-10-18.res: Gene-centric RMA-normalized mRNA expression data.

Differential Gene Expression in Primary Tumors (TCGA)

* Normalized gene expression data of RNASeqV2 was extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered at Jan-05-2015. Only eight cancer types have enough normal control samples for differential expression analysis.
(t test, adjusted p<0.05 (using Benjamini-Hochberg FDR))

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CNV vs Gene Expression Plot

* This plots show the correlation between CNV and gene expression.

: Open all plots for all cancer types

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Gene-Gene Network Information

Co-Expressed gene's network Plot

* Co-Expression network figures were drawn using R package igraph. Only the top 20 genes with the highest correlations were shown.
Red circle: input gene, orange circle: cell metabolism gene, sky circle: other gene

: Open all plots for all cancer types


ANKRD46,ARFGEF1,ATP6V1C1,AZIN1,TRIQK,CPNE3,DPY19L4, EBAG9,RMDN1,FAM91A1,KIAA0196,MTDH,RRM2B,SPAG1, STAU2,EMC2,UBE2W,UBR5,VPS13B,WWP1,ZNF252P	AHCYL2,CAB39,CUL5,EFR3A,EGLN1,FBXL17,FBXO3, FYTTD1,HCN1,IBTK,IDE,KIAA0232,KPNA1,PPTC7, RPS6KA3,RRM2B,STAU2,STRN3,SYNJ2BP,USP38,WDR47

ATP6V1C1,ANKUB1,CPNE3,FAM91A1,GRM5,GUCA1C,IL1RL1, KHDC1L,KIAA0196,KRT1,MTDH,NBN,OR10H4,OSGIN2, PCDH9,PLGLA,RIPK2,RRM2B,STK3,TRAM1,UTS2B	PXYLP1,ALDH7A1,CCDC112,CNOT7,CPNE3,HSDL2,KCNE2, LINC01512,LRPPRC,MEST,METTL15,PLEKHG7,PRSS30P,RRM2B, SKAP2,SLC12A2,STARD7,THNSL1,UPRT,WARS2,ZBTB44

Co-Expressed gene's Protein-protein interaction Network Plot

: Open all plots for all cancer types

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Interacting Genes (from Pathway Commons)

: Open all interacting genes' information including KEGG pathway for all interacting genes from DAVID

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Pharmacological Information for RRM2

Cross-referenced pharmacological DB IDs from Uniprot

DB Category

DB Name

DB's ID and Url link

Drug-Gene Interaction Network

* Gene Centered Interaction Network.

* Drug Centered Interaction Network.

DrugBank ID	Target Name	Drug Groups	Generic Name	Drug Centered Network	Drug Structure
DB00242	ribonucleotide reductase M2	approved; investigational	Cladribine
DB05260	ribonucleotide reductase M2	approved; investigational	Gallium nitrate
DB00987	ribonucleotide reductase M2	approved; investigational	Cytarabine
DB01101	ribonucleotide reductase M2	approved; investigational	Capecitabine
DB00544	ribonucleotide reductase M2	approved	Fluorouracil
DB00130	ribonucleotide reductase M2	approved; nutraceutical; investigational	L-Glutamine
DB00441	ribonucleotide reductase M2	approved	Gemcitabine
DB00515	ribonucleotide reductase M2	approved	Cisplatin
DB01050	ribonucleotide reductase M2	approved	Ibuprofen

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Cross referenced IDs for RRM2

* We obtained these cross-references from Uniprot database. It covers 150 different DBs, 18 categories. http://www.uniprot.org/help/cross_references_section

: Open all cross reference information