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 PROC

Basic gene info.	Gene symbol	PROC
	Gene name	protein C (inactivator of coagulation factors Va and VIIIa)
	Synonyms	APC\|PC\|PROC1\|THPH3\|THPH4
	Cytomap	UCSC genome browser: 2q13-q14
	Genomic location	chr2 :128175995-128186822
	Type of gene	protein-coding
	RefGenes	NM_000312.3,
	Ensembl id	ENSG00000115718
	Description	anticoagulant protein Cautoprothrombin IIAblood coagulation factor XIVprepro-protein Cvitamin K-dependent protein C
	Modification date	20141207
dbXrefs	MIM : 612283
	HGNC : HGNC
	Ensembl : ENSG00000115718
	HPRD : 01466
	Vega : OTTHUMG00000131528
Protein	UniProt: P04070 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PROC
	BioGPS: 5624
	Gene Expression Atlas: ENSG00000115718
	The Human Protein Atlas: ENSG00000115718
Pathway	NCI Pathway Interaction Database: PROC
	KEGG: PROC
	REACTOME: PROC
	ConsensusPathDB
	Pathway Commons: PROC
Metabolism	MetaCyc: PROC
	HUMANCyc: PROC
Regulation	Ensembl's Regulation: ENSG00000115718
	miRBase: chr2 :128,175,995-128,186,822
	TargetScan: NM_000312
	cisRED: ENSG00000115718
Context	iHOP: PROC
	cancer metabolism search in PubMed: PROC
	UCL Cancer Institute: PROC
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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

Cancer Description
Cancer	CGAP: PROC
	Familial Cancer Database: PROC

* 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_PROTEINS

Others
OMIM	176860; phenotype. 612283; gene. 612304; phenotype.
Orphanet	745; Hereditary thrombophilia due to congenital protein C deficiency.
Disease	KEGG Disease: PROC
	MedGen: PROC (Human Medical Genetics with Condition)
	ClinVar: PROC
Phenotype	MGI: PROC (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PROC

Mutations for PROC

* 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 PROC 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

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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=30)	Stat. for Synonymous SNVs (# total SNVs=12)

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
chr2:128185950-128185950	p.R272C	3
chr2:128186037-128186037	p.A301T	2
chr2:128184716-128184716	p.C238C	2
chr2:128186044-128186044	p.L303R	2
chr2:128178901-128178901	p.R38Q	2
chr2:128180872-128180872	p.S141S	2
chr2:128185973-128185973	p.D279D	2
chr2:128178999-128178999	p.E71K	2
chr2:128186241-128186241	p.P369S	2
chr2:128177548-128177548	p.F10F	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		3	1		1		4			4		1			9	3	2	6
# mutation	1	1		3	1		1		4			6		1			12	3	2	7
nonsynonymous SNV		1		3					4					1			9	2	1	4
synonymous SNV	1				1		1					6					3	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
chr2:128186037	p.A301T	2
chr2:128186044	p.L303R	2
chr2:128178989	p.E67D	1
chr2:128186390	p.G418G	1
chr2:128184763	p.E68K	1
chr2:128186171	p.T436T	1
chr2:128178990	p.E71K	1
chr2:128186444	p.C319C	1
chr2:128185950	p.R440H	1
chr2:128186197	p.I112I	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 PROC 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 PROC

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


APCS,APOA4,APOC4,ASGR2,SLC25A47,C8A,C8G, CATSPER1,CRP,F2,F9,G6PC,HAMP,HP, ITIH1,ITIH4,LEAP2,MT1B,PLG,PROC,SERPINC1	A1CF,ANKFN1,ANKRD30B,SMCO3,C8B,CSAG2,FGL1, HABP2,HNF1A,IGFL2,KCNC2,LOC285733,LOC646813,MIA2, OR52M1,PKHD1,PROC,SERPINA4,TMED6,TTLL6,UGT2B15

CNPPD1,C2orf68,MLLT4-AS1,CCDC115,DDX19B,DHRS12,DNAJB2, DNMT3A,FCHSD1,GGT7,GLB1L,IFT172,IHH,ILDR1, MAGED2,NCK2,PROC,TMEM150A,TMEM176A,TMEM44,WBP1	AKAP5,ARHGAP36,CCDC24,CTSE,FCHSD1,HEPACAM2,IP6K2, MCF2L,PP14571,PROC,QPRT,REP15,RORC,TCP10, TMEM98,VSIG2,ZBTB48,ZNF552,ZNF613,ZNF763,ZNF774

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 PROC

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P04070; -.
Chemistry	ChEMBL	CHEMBL4444; -.
Organism-specific databases	PharmGKB	PA33799; -.
Organism-specific databases	CTD	5624; -.

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
DB00170	protein C (inactivator of coagulation factors Va and VIIIa)	approved; nutraceutical	Menadione
DB00464	protein C (inactivator of coagulation factors Va and VIIIa)	approved	Sodium Tetradecyl Sulfate
DB00682	protein C (inactivator of coagulation factors Va and VIIIa)	approved	Warfarin

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Cross referenced IDs for PROC

* 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