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 PRKCA

Basic gene info.	Gene symbol	PRKCA
	Gene name	protein kinase C, alpha
	Synonyms	AAG6\|PKC-alpha\|PKCA\|PRKACA
	Cytomap	UCSC genome browser: 17q22-q23.2
	Genomic location	chr17 :64298925-64806862
	Type of gene	protein-coding
	RefGenes	NM_002737.2,
	Ensembl id	ENSG00000154229
	Description	PKC-Aaging-associated gene 6protein kinase C alpha type
	Modification date	20141222
dbXrefs	MIM : 176960
	HGNC : HGNC
	Ensembl : ENSG00000154229
	HPRD : 01498
	Vega : OTTHUMG00000179533
Protein	UniProt: P17252 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PRKCA
	BioGPS: 5578
	Gene Expression Atlas: ENSG00000154229
	The Human Protein Atlas: ENSG00000154229
Pathway	NCI Pathway Interaction Database: PRKCA
	KEGG: PRKCA
	REACTOME: PRKCA
	ConsensusPathDB
	Pathway Commons: PRKCA
Metabolism	MetaCyc: PRKCA
	HUMANCyc: PRKCA
Regulation	Ensembl's Regulation: ENSG00000154229
	miRBase: chr17 :64,298,925-64,806,862
	TargetScan: NM_002737
	cisRED: ENSG00000154229
Context	iHOP: PRKCA
	cancer metabolism search in PubMed: PRKCA
	UCL Cancer Institute: PRKCA
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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

Cancer Description
Cancer	CGAP: PRKCA
	Familial Cancer Database: PRKCA

* 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_FC_GAMMA_R_MEDIATED_PHAGOCYTOSIS REACTOME_INTEGRATION_OF_ENERGY_METABOLISM REACTOME_METABOLISM_OF_MRNA REACTOME_METABOLISM_OF_RNA

Others
OMIM	176960; gene.
Orphanet
Disease	KEGG Disease: PRKCA
	MedGen: PRKCA (Human Medical Genetics with Condition)
	ClinVar: PRKCA
Phenotype	MGI: PRKCA (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PRKCA

Mutations for PRKCA

* 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
breast	PRKCA	chr17	64426563	64426563	CARD14	chr17	78173073	78173073
NS	PRKCA	chr17	64625760	64625760	SDK2	chr17	71433202	71433202
ovary	PRKCA	chr17	64323211	64323231	PRKCA	chr17	64329335	64329355
ovary	PRKCA	chr17	64431023	64431043	PRKCA	chr17	64439985	64440005
ovary	PRKCA	chr17	64585967	64585987	PRKCA	chr17	64589784	64589804
ovary	PRKCA	chr17	64589749	64589769	UHRF1BP1L	chr12	100449860	100449880
ovary	PRKCA	chr17	64784501	64784521		chr4	190179231	190179251
pancreas	PRKCA	chr17	64354257	64354277	PRKCA	chr17	64356707	64356727
pancreas	PRKCA	chr17	64354772	64354792	DCAF7	chr17	61629388	61629408
pancreas	PRKCA	chr17	64355762	64355782	QRICH2	chr17	74275749	74275769
pancreas	PRKCA	chr17	64390214	64390234		chr17	75863079	75863099
pancreas	PRKCA	chr17	64477847	64477867		chr17	47640527	47640547

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 PRKCA 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
BF854872	PRKCA	1	140	17	64571808	64571947	SLC45A3	136	310	1	205633006	205633180
M12996	G6PD	1	1671	X	153759627	153763408	PRKCA	1664	2439	17	64806066	64806841
L13387	PRKCA	1	682	17	64410407	64411088	PAFAH1B1	683	2749	17	2570340	2586175
AK098118	PRKCA	1	2037	17	64682637	64684673	LYZ	2032	2662	12	69747383	69748013
BG998534	PRKCA	26	267	17	64327025	64327270	PBX1	260	400	1	164712457	164712597
CV427033	PRKCA	1	236	17	64690984	64691219	ATP2A2	228	405	12	110759445	110759622
BF665493	PRKCA	1	387	17	64511411	64511798	GALNT13	368	394	2	154989282	154989308
BF815383	ALG5	4	306	13	37524095	37539828	PRKCA	306	486	17	64524798	64524978

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	ns	ovary	pancre	prost	skin	stoma	thyro	urina
Total # sample	25	2		2		1	5		1	1				1	1		1
GAIN (# sample)	24	2		2		1	2			1				1	1		1
LOSS (# sample)	1						3		1

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=6

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=62)	Stat. for Synonymous SNVs (# total SNVs=30)

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
chr17:64738759-64738759	p.V469I	4
chr17:64785022-64785022	p.E593E	3
chr17:64637478-64637478	p.P98P	3
chr17:64783070-64783070	p.E564G	2
chr17:64683239-64683239	p.N182fs*2	2
chr17:64492367-64492367	p.S85F	2
chr17:64685078-64685078	p.L277L	2
chr17:64641554-64641554	p.G152R	2
chr17:64737785-64737785	p.A444V	2
chr17:64685162-64685162	p.F305F	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=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	2		1	13	2		3		2			11	5	2			11	4		12
# mutation	2		1	11	2		3		2			12	5	2			11	4		14
nonsynonymous SNV	1		1	6	2		2					7	5	1			8	3		9
synonymous SNV	1			5			1		2			5		1			3	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
chr17:64299066	p.E33Q	3
chr17:64637478	p.P98P	3
chr17:64728899	p.D338N	2
chr17:64637530	p.G152R	2
chr17:64734896	p.F415F	2
chr17:64641554	p.D116N	2
chr17:64685162	p.F305F	2
chr17:64683246	p.L668L	1
chr17:64782999	p.A12A	1
chr17:64299005	p.C135C	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 PRKCA 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 PRKCA

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.

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Protein Expression Plot (RPPA)

*RPPA protein expression data were extracted from TCPA (The Cancer Proteome Atlas). Normalized data based on replicated based normalization (RBN) was used to draw following figures.

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


ACAN,ANKH,CHST3,DEFB127,ENPP6,FNDC3B,GLS, IFNAR2,MAML2,MFGE8,NRP2,PGM5P2,PMP2,PRKCA, PROS1,PTPN14,SLC23A2,SOX6,TIAM2,TRPV4,ZC3H12C	AKT3,ANP32E,ANTXR1,DPYSL3,GRIN2A,HDAC4,IL7, KCNJ16,KCNJ2,KIAA1024,MOXD1,MUC16,OSMR,PRICKLE1, PRKCA,PROS1,SCN3A,SOCS5,STAC,TLE4,TRPC1

ANKRD36BP1,APPBP2,ASH1L,BPTF,CLTC,CPD,DCAF7, DYRK2,ERN1,HELZ,HIPK1,KIAA1211,LOC651250,MAGI1, MED13,NCOA1,PHF12,PRKCA,RAPH1,SP1,USP32	AKAP6,BNC2,METTL24,DMD,DOCK3,CCSER2,ITPKB, JMY,KCNB1,CTIF,MYH11,NBEA,NRXN3,TENM1, TENM3___TENM1,PIP5K1C,PRICKLE2,PRKCA,SVIL,TLN1,TSPAN18

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 PRKCA

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P17252; -.
Chemistry	ChEMBL	CHEMBL2096620; -.
Chemistry	GuidetoPHARMACOLOGY	1482; -.
Organism-specific databases	PharmGKB	PA33759; -.
Organism-specific databases	CTD	5578; -.

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
DB00144	protein kinase C, alpha	approved; nutraceutical	Phosphatidylserine
DB00163	protein kinase C, alpha	approved; nutraceutical	Vitamin E
DB00945	protein kinase C, alpha	approved	Acetylsalicylic acid
DB00675	protein kinase C, alpha	approved	Tamoxifen
DB01115	protein kinase C, alpha	approved	Nifedipine
DB00877	protein kinase C, alpha	approved; investigational	Sirolimus
DB00864	protein kinase C, alpha	approved; investigational	Tacrolimus
DB00608	protein kinase C, alpha	approved	Chloroquine
DB00171	protein kinase C, alpha	approved; nutraceutical	Adenosine triphosphate
DB00441	protein kinase C, alpha	approved	Gemcitabine
DB01001	protein kinase C, alpha	approved	Salbutamol
DB00125	protein kinase C, alpha	approved; nutraceutical	L-Arginine
DB00155	protein kinase C, alpha	approved; nutraceutical	L-Citrulline
DB00435	protein kinase C, alpha	approved	Nitric Oxide

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Cross referenced IDs for PRKCA

* 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