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 PROS1

Basic gene info.	Gene symbol	PROS1
	Gene name	protein S (alpha)
	Synonyms	PROS\|PS21\|PS22\|PS23\|PS24\|PS25\|PSA\|THPH5\|THPH6
	Cytomap	UCSC genome browser: 3q11.2
	Genomic location	chr3 :93591880-93692934
	Type of gene	protein-coding
	RefGenes	NM_000313.3,
	Ensembl id	ENSG00000184500
	Description	protein Savitamin K-dependent plasma protein Svitamin K-dependent protein S
	Modification date	20141207
dbXrefs	MIM : 176880
	HGNC : HGNC
	Ensembl : ENSG00000184500
	HPRD : 01473
	Vega : OTTHUMG00000150354
Protein	UniProt: P07225 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PROS1
	BioGPS: 5627
	Gene Expression Atlas: ENSG00000184500
	The Human Protein Atlas: ENSG00000184500
Pathway	NCI Pathway Interaction Database: PROS1
	KEGG: PROS1
	REACTOME: PROS1
	ConsensusPathDB
	Pathway Commons: PROS1
Metabolism	MetaCyc: PROS1
	HUMANCyc: PROS1
Regulation	Ensembl's Regulation: ENSG00000184500
	miRBase: chr3 :93,591,880-93,692,934
	TargetScan: NM_000313
	cisRED: ENSG00000184500
Context	iHOP: PROS1
	cancer metabolism search in PubMed: PROS1
	UCL Cancer Institute: PROS1
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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Phenotypic Information for PROS1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PROS1
	Familial Cancer Database: PROS1

* 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	176880; gene. 612336; phenotype. 614514; phenotype.
Orphanet	743; Hereditary thrombophilia due to congenital protein S deficiency.
Disease	KEGG Disease: PROS1
	MedGen: PROS1 (Human Medical Genetics with Condition)
	ClinVar: PROS1
Phenotype	MGI: PROS1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PROS1

Mutations for PROS1

* 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

There's no inter-chromosomal structural variation.

- 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	PROS1	chr3	93647956	93647976	PROS1	chr3	93648128	93648148
ovary	PROS1	chr3	93676151	93676171		chr3	73753822	73753842

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 PROS1 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
BE185151	SDC1	12	180	2	20401901	20402069	PROS1	176	433	3	93628822	93629079
AW579277	PROS1	1	237	3	93678727	93678963	GLUL	231	294	1	182353484	182353547

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=6

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=111)	Stat. for Synonymous SNVs (# total SNVs=22)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=1)
There's no deleted 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
chr3:93615439-93615439	p.R316C	5
chr3:93646100-93646100	p.P76P	3
chr3:93624637-93624637	p.D198Y	2
chr3:93598107-93598107	p.R515H	2
chr3:93611862-93611862	p.G357E	2
chr3:93624648-93624648	p.S194*	2
chr3:93598108-93598108	p.R515C	2
chr3:93603660-93603660	p.Q468H	2
chr3:93611868-93611868	p.R355H	2
chr3:93605212-93605212	p.P431S	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	4	1		12	2		4		2	2		21	7	2		1	13	11	1	17
# mutation	4	1		15	2		4		2	2		24	7	2		1	13	11	1	24
nonsynonymous SNV	4	1		11	1		4		2	2		21	5	2		1	12	7	1	18
synonymous SNV				4	1							3	2				1	4		6

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
chr3:93615439	p.R515H	3
chr3:93598107	p.R316C	3
chr3:93595919	p.S587S	2
chr3:93617331	p.K270N	2
chr3:93646100	p.P76P	2
chr3:93615521	p.S387F	1
chr3:93624973	p.K296N	1
chr3:93603712	p.L236R	1
chr3:93605341	p.S140S	1
chr3:93619656	p.L619L	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 PROS1 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 PROS1

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


ABCA6,ARHGAP20,CAV1,COL14A1,ERG,FAM126A,FAT4, FOXO1,FREM1,JAM2,KCTD12,LHFP,LPCAT2,MYLK, PKD2,PLSCR4,PROS1,RHOJ,SPARCL1,TNS1,TSHZ2	AKT3,ANTXR1,CALD1,CTSK,CTSO,CXCL12,DCN, DPYSL2,FKBP7,IFI16,IL33,NT5E,OGN,OMD, PDCD1LG2,PDGFD,PROS1,PTGFR,SGCE,TFPI,UST

ARL13B,BBS9,BBX,DYNC2H1,FOXO1,GNB5,GPR137B, HINT3,NAV1,PAM,PLEKHA4,PLSCR4,PROS1,PRRG1, RNF144B,SDCBP,SERINC1,SHISA2,SNPH,TMEM233,TMOD2	C10orf120,IZUMO2,TDRP,CELA2B,CGB2,COX7B2,FAM153B, GJA10,GNA14,KCTD12,LRRC36,MC2R,OPN1LW,PDP1, PROP1,PROS1,SLITRK5,SNORA38B,TDRD1,UTS2,WFDC6

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 PROS1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA33809; -.
Organism-specific databases	CTD	5627; -.

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 S (alpha)	approved; nutraceutical	Menadione
DB00464	protein S (alpha)	approved	Sodium Tetradecyl Sulfate
DB00682	protein S (alpha)	approved	Warfarin

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Cross referenced IDs for PROS1

* 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