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 PPARA

Basic gene info.	Gene symbol	PPARA
	Gene name	peroxisome proliferator-activated receptor alpha
	Synonyms	NR1C1\|PPAR\|PPARalpha\|hPPAR
	Cytomap	UCSC genome browser: 22q13.31
	Genomic location	chr22 :46546498-46639653
	Type of gene	protein-coding
	RefGenes	NM_001001928.2, NM_005036.4,NM_001001929.2,NM_001001930.2,NM_032644.3,
	Ensembl id	ENSG00000186951
	Description	PPAR-alphanuclear receptor subfamily 1 group C member 1peroxisome proliferative activated receptor, alphaperoxisome proliferator-activated nuclear receptor alpha variant 3
	Modification date	20141222
dbXrefs	MIM : 170998
	HGNC : HGNC
	Ensembl : ENSG00000186951
	HPRD : 01369
	Vega : OTTHUMG00000150443
Protein	UniProt: Q07869 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PPARA
	BioGPS: 5465
	Gene Expression Atlas: ENSG00000186951
	The Human Protein Atlas: ENSG00000186951
Pathway	NCI Pathway Interaction Database: PPARA
	KEGG: PPARA
	REACTOME: PPARA
	ConsensusPathDB
	Pathway Commons: PPARA
Metabolism	MetaCyc: PPARA
	HUMANCyc: PPARA
Regulation	Ensembl's Regulation: ENSG00000186951
	miRBase: chr22 :46,546,498-46,639,653
	TargetScan: NM_001001928
	cisRED: ENSG00000186951
Context	iHOP: PPARA
	cancer metabolism search in PubMed: PPARA
	UCL Cancer Institute: PPARA
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of PPARA in cancer cell metabolism	1. Wang W-LW, Welsh J, Tenniswood M (2013) 1, 25-Dihydroxyvitamin D 3 modulates lipid metabolism in prostate cancer cells through miRNA mediated regulation of PPARA. The Journal of steroid biochemistry and molecular biology 136: 247-251. go to article

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

Cancer Description
Cancer	CGAP: PPARA
	Familial Cancer Database: PPARA

* 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_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	170998; gene+phenotype.
Orphanet
Disease	KEGG Disease: PPARA
	MedGen: PPARA (Human Medical Genetics with Condition)
	ClinVar: PPARA
Phenotype	MGI: PPARA (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PPARA

Mutations for PPARA

* 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	PPARA	chr22	46572720	46572740		chr22	46259135	46259155
ovary	PPARA	chr22	46579824	46579844	CYTH4	chr22	37699353	37699373
ovary	PPARA	chr22	46598322	46598342		chr22	46260488	46260508
ovary	PPARA	chr22	46634367	46634387	PPARA	chr22	46634428	46634448

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 PPARA 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
BF911067	PPARA	4	96	22	46559133	46559225	PPARA	95	392	22	46553064	46553360
AA807786	PPARA	8	135	22	46637688	46637815	PPARA	133	454	22	46637369	46637692
AI079573	PPARA	1	164	22	46637648	46637811	AP2M1	162	538	3	183901431	183901807

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=26)	Stat. for Synonymous SNVs (# total SNVs=15)

Stat. for Deletions (# total SNVs=4)	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
chr22:46614210-46614212	p.R141delR	2
chr22:46614211-46614211	p.R141C	2
chr22:46628123-46628123	p.I382I	2
chr22:46627961-46627961	p.D328D	2
chr22:46614234-46614234	p.K148N	2
chr22:46628131-46628131	p.C385S	2
chr22:46628050-46628050	p.K358R	2
chr22:46611088-46611088	p.S76L	2
chr22:46627814-46627814	p.T279T	2
chr22:46615714-46615714	p.R172C	2

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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		7	1				1			3	2	1			14	4	1	5
# mutation		1		7	1				1			3	2	1			13	4	1	6
nonsynonymous SNV		1		5	1							1	1	1			7	3	1	1
synonymous SNV				2					1			2	1				6	1		5

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
chr22:46611088	p.S76L,PPARA	2
chr22:46627961	p.D328D,PPARA	2
chr22:46615710	p.G62D,PPARA	1
chr22:46594462	p.H159Y,PPARA	1
chr22:46628055	p.L370L,PPARA	1
chr22:46614165	p.T69M,PPARA	1
chr22:46615854	p.V164V,PPARA	1
chr22:46594465	p.I375I,PPARA	1
chr22:46628087	p.T71T,PPARA	1
chr22:46614173	p.G165W,PPARA	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 PPARA 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 PPARA

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


ANKRD36BP1,ARHGAP21,CCDC82,CHST3,CLCN4,CREB3L2,FMNL2, FNDC3B,IFNAR2,JOSD1,JRKL,KIAA1804,MAML2,MRAS, NCK1,PKDREJ,PPARA,PTPN14,SOS1,TCF20,ZNF462	ACAT1,ADHFE1,ATP5B,TCAIM,ADCK3,ETFDH,HADHB, HECTD1,KIAA0368,L2HGDH,NRD1,PDHX,PHYH,PPARA, RMND5A,RRAGD,SLC2A4,SLC41A1,SOX6,SUCLA2,UQCRC2

ANKRD17,C9orf129,CGN,CMTM4,DENND4C,ENTPD5,INADL, KIAA1109,KIAA1671,KIAA2018,MAGI3,MYO7B,PPARA,PTPRF, PUM1,RBM47,RREB1,SH3D19,SPG11,TCF20,ZBED4	AGPAT3,ALDH18A1,ATP1A1,DNMBP,DOCK5,KBTBD11,KIF3B, MARCH6,NHSL1,PLXNA2,POR,PPARA,PTPRK,SEMA6A, TGOLN2,TNIK,UBE4A,VAV2,VIL1,ZCCHC14,ZZEF1

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 PPARA

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	Q07869; -.
Chemistry	ChEMBL	CHEMBL239; -.
Chemistry	GuidetoPHARMACOLOGY	593; -.
Organism-specific databases	PharmGKB	PA280; -.
Organism-specific databases	CTD	5465; -.

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
DB00636	peroxisome proliferator-activated receptor alpha	approved	Clofibrate
DB01039	peroxisome proliferator-activated receptor alpha	approved	Fenofibrate
DB01241	peroxisome proliferator-activated receptor alpha	approved	Gemfibrozil
DB01393	peroxisome proliferator-activated receptor alpha	approved	Bezafibrate
DB01890	peroxisome proliferator-activated receptor alpha	experimental	Deoxy-Bigchap
DB07215	peroxisome proliferator-activated receptor alpha	experimental	2-METHYL-2-(4-{[({4-METHYL-2-[4-(TRIFLUOROMETHYL)PHENYL]-1,3-THIAZOL-5-YL}CARBONYL)AMINO]METHYL}PHENOXY)PROPANOIC ACID
DB07724	peroxisome proliferator-activated receptor alpha	experimental	3-{5-methoxy-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}propanoic acid
DB08483	peroxisome proliferator-activated receptor alpha	experimental	(2S)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl}propanoic acid
DB00724	peroxisome proliferator-activated receptor alpha	approved; investigational	Imiquimod

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Cross referenced IDs for PPARA

* 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