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 PDK3

Basic gene info.	Gene symbol	PDK3
	Gene name	pyruvate dehydrogenase kinase, isozyme 3
	Synonyms	CMTX6\|GS1-358P8.4
	Cytomap	UCSC genome browser: Xp22.11
	Genomic location	chrX :24483343-24552542
	Type of gene	protein-coding
	RefGenes	NM_001142386.2, NM_005391.4,
	Ensembl id	ENSG00000067992
	Description	[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrialpyruvate dehydrogenase kinase, isoenzyme 3pyruvate dehydrogenase, lipoamide, kinase isozyme 3, mitochondrial
	Modification date	20141207
dbXrefs	MIM : 300906
	HGNC : HGNC
	Ensembl : ENSG00000067992
	HPRD : 03956
	Vega : OTTHUMG00000021269
Protein	UniProt: Q15120 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PDK3
	BioGPS: 5165
	Gene Expression Atlas: ENSG00000067992
	The Human Protein Atlas: ENSG00000067992
Pathway	NCI Pathway Interaction Database: PDK3
	KEGG: PDK3
	REACTOME: PDK3
	ConsensusPathDB
	Pathway Commons: PDK3
Metabolism	MetaCyc: PDK3
	HUMANCyc: PDK3
Regulation	Ensembl's Regulation: ENSG00000067992
	miRBase: chrX :24,483,343-24,552,542
	TargetScan: NM_001142386
	cisRED: ENSG00000067992
Context	iHOP: PDK3
	cancer metabolism search in PubMed: PDK3
	UCL Cancer Institute: PDK3
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of PDK3 in cancer cell metabolism	1. Kluza J, Corazao-Rozas P, Touil Y, Jendoubi M, Maire C, et al. (2012) Inactivation of the HIF-1α/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidants. Cancer research 72: 5035-5047. go to article 2. Prigione A, Rohwer N, Hoffmann S, Mlody B, Drews K, et al. (2014) HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1–3 and PKM2. Stem Cells 32: 364-376. go to article

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Phenotypic Information for PDK3(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PDK3
	Familial Cancer Database: PDK3

* 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
REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE REACTOME_PYRUVATE_METABOLISM

Others
OMIM	300905; phenotype. 300906; gene.
Orphanet	352675; X-linked Charcot-Marie-Tooth disease type 6.
Disease	KEGG Disease: PDK3
	MedGen: PDK3 (Human Medical Genetics with Condition)
	ClinVar: PDK3
Phenotype	MGI: PDK3 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PDK3

Mutations for PDK3

* 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 PDK3 related fusion information.

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

AV755280

PDK3

149

24518545

24518622

PDK3

150

505

24517518

24517868

BU674003

PDK3

220

24568381

24568583

PDK3

219

341

24568157

24568279

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=7

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=42)	Stat. for Synonymous SNVs (# total SNVs=14)

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
chr23:24537111-24537111	p.E219E	4
chr23:24552052-24552052	p.S362T	2
chr23:24521580-24521580	p.R153W	2
chr23:24521596-24521596	p.R158H	2
chr23:24546235-24546235	p.R299C	2
chr23:24544369-24544369	p.H243R	2
chr23:24545733-24545733	p.E265K	1
chr23:24512948-24512948	p.L66F	1
chr23:24521544-24521544	p.P141S	1
chr23:24537110-24537110	p.E219A	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=4

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		11					1			4	3	2		1	5	3	1	10
# mutation		1		6					1			4	3	2		1	5	3	1	11
nonsynonymous SNV				5					1			3	3	2			4	2	1	8
synonymous SNV		1		2								1				1	1	1		3

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
chrX:24537111	p.E219E,PDK3	5
chrX:24546235	p.R299C,PDK3	3
chrX:24552052	p.S362T,PDK3	2
chrX:24557271	p.D140H,PDK3	1
chrX:24516996	p.F324L,PDK3	1
chrX:24537108	p.P141S,PDK3	1
chrX:24549803	p.S331S,PDK3	1
chrX:24521458	p.N157D,PDK3	1
chrX:24521470	p.L170L,PDK3	1
chrX:24537120	p.S362S,PDK3	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 PDK3 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 PDK3

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


BCAR4,ABRACL,FAM171A1,FOXC1,HORMAD1,ID4,LMAN1L, NUDT3,OGFRL1,OR5AU1,PDK3,PIR,PRM1,PRM2, PTCHD1,RIPK2,RNASE13,SLC26A7,STATH,TNP2,TPPP2	ABI2,B3GALNT1,CXADR,DSC2,EXPH5,ITGA2,KLHL42, LRRC8D,MTMR1,OAT,PDK3,PRKCI,RBBP4,PTBP3, SLC11A2,SLC9A7,SRPK1,SUDS3,TRIM59,ZNF286A,ZNF93

AIFM1,APEX2,APOO,DKC1,ELK1,FANCB,FTSJ1, HCCS,HPRT1,NDUFB11,NKAP,NSDHL,PDK3,JADE3, PRPS1,PRPS2,SMS,SUV39H1,TIMM8A,TMLHE,VBP1	CALM1,CDS2,EFR3A,EXOC6B,FREM1,HOXC10,HOXC4, IRS4,KCTD4,MEGF9,MYLK3,NR1D1,NRBP1,OR51E1, PDK3,PSG5,RARB,RPS6KA5,SEC23A,TAC3,ZACN

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 PDK3

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	ChEMBL	CHEMBL2096665; -.
Organism-specific databases	PharmGKB	PA33156; -.
Organism-specific databases	CTD	5165; -.

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
DB03758	pyruvate dehydrogenase kinase, isozyme 3	experimental	Radicicol
DB03760	pyruvate dehydrogenase kinase, isozyme 3	experimental	Dihydrolipoic Acid

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Cross referenced IDs for PDK3

* 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