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 TK1

Basic gene info.	Gene symbol	TK1
	Gene name	thymidine kinase 1, soluble
	Synonyms	TK2
	Cytomap	UCSC genome browser: 17q23.2-q25.3
	Genomic location	chr17 :76170159-76183285
	Type of gene	protein-coding
	RefGenes	NM_003258.4,
	Ensembl id	ENSG00000167900
	Description	thymidine kinase 1 soluble isoformthymidine kinase, cytosolicthymidine kinase-1
	Modification date	20141207
dbXrefs	MIM : 188300
	HGNC : HGNC
	Ensembl : ENSG00000167900
	HPRD : 01771
	Vega : OTTHUMG00000150674
Protein	UniProt: P04183 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_TK1
	BioGPS: 7083
	Gene Expression Atlas: ENSG00000167900
	The Human Protein Atlas: ENSG00000167900
Pathway	NCI Pathway Interaction Database: TK1
	KEGG: TK1
	REACTOME: TK1
	ConsensusPathDB
	Pathway Commons: TK1
Metabolism	MetaCyc: TK1
	HUMANCyc: TK1
Regulation	Ensembl's Regulation: ENSG00000167900
	miRBase: chr17 :76,170,159-76,183,285
	TargetScan: NM_003258
	cisRED: ENSG00000167900
Context	iHOP: TK1
	cancer metabolism search in PubMed: TK1
	UCL Cancer Institute: TK1
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of TK1 in cancer cell metabolism	1. Brockenbrough JS, Morihara JK, Hawes SE, Stern JE, Rasey JS, et al. (2009) Thymidine kinase 1 and thymidine phosphorylase expression in non-small-cell lung carcinoma in relation to angiogenesis and proliferation. Journal of Histochemistry & Cytochemistry 57: 1087-1097. go to article 2. O’Brien PJ, Lee M, Spilker ME, Zhang CC, Yan Z, et al. (2013) Monitoring metabolic responses to chemotherapy in single cells and tumors using nanostructure-initiator mass spectrometry (NIMS) imaging. Cancer & metabolism 1: 1-14. go to article

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Phenotypic Information for TK1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: TK1
	Familial Cancer Database: TK1

* 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_PYRIMIDINE_METABOLISM KEGG_DRUG_METABOLISM_OTHER_ENZYMES REACTOME_METABOLISM_OF_NUCLEOTIDES REACTOME_PYRIMIDINE_METABOLISM

Others
OMIM	188300; gene.
Orphanet
Disease	KEGG Disease: TK1
	MedGen: TK1 (Human Medical Genetics with Condition)
	ClinVar: TK1
Phenotype	MGI: TK1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: TK1

Mutations for TK1

* 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

- Statistics for Tissue and Mutation type

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- For Inter-chromosomal Variations

* Inter-chromosomal variantions includes 'interchromosomal amplicon to amplicon', 'interchromosomal amplicon to non-amplified dna', 'interchromosomal insertion', 'Interchromosomal unknown type'.

- For Intra-chromosomal Variations

* Intra-chromosomal variantions includes 'intrachromosomal amplicon to amplicon', 'intrachromosomal amplicon to non-amplified dna', 'intrachromosomal deletion', 'intrachromosomal fold-back inversion', 'intrachromosomal inversion', 'intrachromosomal tandem duplication', 'Intrachromosomal unknown type', 'intrachromosomal with inverted orientation', 'intrachromosomal with non-inverted orientation'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
ovary	TK1	chr17	76171285	76171305		chr22	24198303	24198323
pancreas	TK1	chr17	76171363	76171383	RECQL5	chr17	73635230	73635250

cf) Tissue number; Tissue name (1;Breast, 2;Central_nervous_system, 3;Haematopoietic_and_lymphoid_tissue, 4;Large_intestine, 5;Liver, 6;Lung, 7;Ovary, 8;Pancreas, 9;Prostate, 10;Skin, 11;Soft_tissue, 12;Upper_aerodigestive_tract)

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows TK1 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
BE729700	UBTF	1	125	17	42283359	42283484	TK1	124	714	17	76171097	76183116
AW376086	CALCOCO1	21	315	12	54105020	54105313	TK1	307	671	17	76176597	76176963
BG118054	TK1	25	237	17	76170520	76170734	CAMTA1	236	304	1	7100596	7215212

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=2

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=9)	Stat. for Synonymous SNVs (# total SNVs=1)

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
chr17:76181214-76181214	p.Q44L	1
chr17:76171139-76171139	p.E169K	1
chr17:76171144-76171144	p.G167D	1
chr17:76171214-76171214	p.E144K	1
chr17:76171626-76171626	p.G126V	1
chr17:76171657-76171657	p.G116R	1
chr17:76170848-76170848	p.A233T	1
chr17:76171679-76171679	p.F108L	1
chr17:76170913-76170913	p.K211T	1
chr17:76178695-76178695	p.V93A	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			1														2	2	4
# mutation	2			1														2	2	4
nonsynonymous SNV	1			1														2	2	3
synonymous SNV	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
chr17:76171139	p.G116R	1
chr17:76171144	p.D83E	1
chr17:76171657	p.A78T	1
chr17:76178724	p.A233T	1
chr17:76178741	p.K211T	1
chr17:76170848	p.E204D	1
chr17:76170913	p.S194P	1
chr17:76170933	p.V184V	1
chr17:76170965	p.E169E	1
chr17:76170993	p.E169K	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 TK1 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 TK1

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


BIRC5,C17orf89,CCDC137,CENPM,DUS1L,EPR1,GJA10, GPS1,HCCS,JMJD6,MRPL12,MRPL38,P4HB,PCYT2, PIR,PKMYT1,SLC25A10,STRA13,SYNGR2,ALYREF,TK1	ASF1B,BIRC5,CDC45,CDCA5,CENPM,E2F1,EPR1, FAM111B,FEN1,GALE,KIFC1,PKMYT1,POC1A,PYCR1, RAD51,RAD54L,RECQL4,RRM2,TK1,UHRF1,ZWINT

ASF1B,BIRC5,C17orf53,CDC45,CENPM,EIF4A3,EPR1, FEN1,H2AFX,HAUS8,LRRC59,MCM5,MRPL27,RAD51, RRM2,SLC25A19,STRA13,ALYREF,TK1,TUBA1B,WDR34	ASF1B,CDCA5,CDCA8,CENPM,CEP55,CHAF1B,EXO1, FEN1,GINS4,MELK,NCAPH,OIP5,ORC1,POC1A, RAD54L,RNASEH2A,RRM2,SKA3,TK1,TRIP13,TYMS

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 TK1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P04183; -.
Chemistry	ChEMBL	CHEMBL2883; -.
Organism-specific databases	PharmGKB	PA352; -.
Organism-specific databases	CTD	7083; -.

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
DB01692	thymidine kinase 1, soluble	experimental	Dithioerythritol
DB02452	thymidine kinase 1, soluble	experimental	Thymidine-5'-Triphosphate
DB01101	thymidine kinase 1, soluble	approved; investigational	Capecitabine
DB00544	thymidine kinase 1, soluble	approved	Fluorouracil
DB02745	thymidine kinase 1, soluble	experimental	Uridine
DB00495	thymidine kinase 1, soluble	approved	Zidovudine
DB01033	thymidine kinase 1, soluble	approved	Mercaptopurine
DB00563	thymidine kinase 1, soluble	approved	Methotrexate
DB01050	thymidine kinase 1, soluble	approved	Ibuprofen

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Cross referenced IDs for TK1

* 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