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 RRM1

Basic gene info.	Gene symbol	RRM1
	Gene name	ribonucleotide reductase M1
	Synonyms	R1\|RIR1\|RR1
	Cytomap	UCSC genome browser: 11p15.5
	Genomic location	chr11 :4115923-4160106
	Type of gene	protein-coding
	RefGenes	NM_001033.3,
	Ensembl id	ENSG00000167325
	Description	ribonucleoside-diphosphate reductase large subunitribonucleoside-diphosphate reductase subunit M1ribonucleotide reductase M1 polypeptideribonucleotide reductase, R1 subunit
	Modification date	20141207
dbXrefs	MIM : 180410
	HGNC : HGNC
	Ensembl : ENSG00000167325
	HPRD : 01588
	Vega : OTTHUMG00000133361
Protein	UniProt: P23921 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_RRM1
	BioGPS: 6240
	Gene Expression Atlas: ENSG00000167325
	The Human Protein Atlas: ENSG00000167325
Pathway	NCI Pathway Interaction Database: RRM1
	KEGG: RRM1
	REACTOME: RRM1
	ConsensusPathDB
	Pathway Commons: RRM1
Metabolism	MetaCyc: RRM1
	HUMANCyc: RRM1
Regulation	Ensembl's Regulation: ENSG00000167325
	miRBase: chr11 :4,115,923-4,160,106
	TargetScan: NM_001033
	cisRED: ENSG00000167325
Context	iHOP: RRM1
	cancer metabolism search in PubMed: RRM1
	UCL Cancer Institute: RRM1
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of RRM1 in cancer cell metabolism	1. Nakano Y, Tanno S, Koizumi K, Nishikawa T, Nakamura K, et al. (2007) Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells. British journal of cancer 96: 457-463. go to article 2. Germano A, Rapa I, Volante M, De Francia S, Migliore C, et al. (2015) RRM1 modulates mitotane activity in adrenal cancer cells interfering with its metabolization. Molecular and cellular endocrinology 401: 105-110. go to article

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Phenotypic Information for RRM1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: RRM1
	Familial Cancer Database: RRM1

* 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	180410; gene.
Orphanet
Disease	KEGG Disease: RRM1
	MedGen: RRM1 (Human Medical Genetics with Condition)
	ClinVar: RRM1
Phenotype	MGI: RRM1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: RRM1

Mutations for RRM1

* 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 RRM1 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
AU125246	PHF23	1	229	17	7139380	7139608	RRM1	230	882	11	4144413	4150383
H90823	RRM1	1	152	11	4125333	4125639	RRM1	146	401	11	4125492	4125742

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

Mutation type/ Tissue ID

brca

cns

cerv

endome

haematopo

kidn

Lintest

liver

lung

ovary

pancre

prost

skin

stoma

thyro

urina

Total # sample

GAIN (# sample)

LOSS (# sample)

cf) Tissue ID; Tissue type (1; Breast, 2; Central_nervous_system, 3; Cervix, 4; Endometrium, 5; Haematopoietic_and_lymphoid_tissue, 6; Kidney, 7; Large_intestine, 8; Liver, 9; Lung, 10; NS, 11; Ovary, 12; Pancreas, 13; Prostate, 14; Skin, 15; Stomach, 16; Thyroid, 17; Urinary_tract)

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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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=29)	Stat. for Synonymous SNVs (# total SNVs=9)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=0)
There's no deleted snv.	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
chr11:4127339-4127339	p.T58A	3
chr11:4159457-4159457	p.T741T	3
chr11:4148290-4148290	p.R499H	2
chr11:4159466-4159466	p.A744A	2
chr11:4142895-4142895	p.D313G	1
chr11:4159522-4159522	p.V763A	1
chr11:4133141-4133141	p.P167S	1
chr11:4156448-4156448	p.A713V	1
chr11:4142904-4142904	p.K316T	1
chr11:4159538-4159538	p.E768D	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=2

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	1	2		4			1		2			7	2	1			5	8		3
# mutation	1	2		4			1		2			9	2	1			5	9		4
nonsynonymous SNV	1	2		4			1		2			8	2	1			3	6		2
synonymous SNV												1					2	3		2

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
chr11:4148290	p.R499H	2
chr11:4144429	p.G259D	1
chr11:4153577	p.L584L	1
chr11:4133248	p.P274Q	1
chr11:4159538	p.L611L	1
chr11:4144499	p.V13V	1
chr11:4123242	p.P294L	1
chr11:4153625	p.R627S	1
chr11:4133255	p.I22F	1
chr11:4144502	p.D313G	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 RRM1 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 RRM1

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


CDK2,CKAP2L,CKAP5,DHX9,ECT2,HELLS,IPO7, KIF11,KIF18A,KNTC1,LMNB1,MCM6,MSH6,NUP98, NUSAP1,PRIM1,RACGAP1,RRM1,SMC2,WDR76,ZNF367	ABCB7,COPS2,COX15,CSNK2A1,CSRP2BP,DDX6,DYM, EIF4B,EPRS,ST13P4,IPO5,LRPPRC,MTIF2,NBAS, RPA1,RRM1,TNPO3,TOMM70A,UBE4B,YME1L1,ZFYVE9

BUB1B,CDC7,CDCA5,CHEK1,E2F8,EXO1,FEN1, HELLS,KIF11,KIF15,KIF18A,MCM10,MCM6,NCAPD3, NCAPG,NCAPH,PLK4,RACGAP1,RRM1,SGOL1,ZWINT	ATAD2,BRCA1,BUB1B,CDCA5,CENPI,CKAP2L,DIAPH3, EXO1,FAM111B,FEN1,GINS4,HELLS,KIF11,KIF23, LMNB1,MTHFD1,NCAPD3,NCAPG2,NCAPH,RRM1,SMC2

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 RRM1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P23921; -.
Chemistry	ChEMBL	CHEMBL2095215; -.
Chemistry	GuidetoPHARMACOLOGY	2630; -.
Organism-specific databases	PharmGKB	PA298; -.
Organism-specific databases	CTD	6240; -.

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 M1	approved; investigational	Cladribine
DB00441	ribonucleotide reductase M1	approved	Gemcitabine
DB00631	ribonucleotide reductase M1	approved; investigational	Clofarabine
DB01005	ribonucleotide reductase M1	approved	Hydroxyurea
DB01073	ribonucleotide reductase M1	approved	Fludarabine
DB00987	ribonucleotide reductase M1	approved; investigational	Cytarabine
DB01101	ribonucleotide reductase M1	approved; investigational	Capecitabine
DB00544	ribonucleotide reductase M1	approved	Fluorouracil
DB00130	ribonucleotide reductase M1	approved; nutraceutical; investigational	L-Glutamine
DB00515	ribonucleotide reductase M1	approved	Cisplatin

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Cross referenced IDs for RRM1

* 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