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 P4HB

Basic gene info.	Gene symbol	P4HB
	Gene name	prolyl 4-hydroxylase, beta polypeptide
	Synonyms	DSI\|ERBA2L\|GIT\|P4Hbeta\|PDI\|PDIA1\|PHDB\|PO4DB\|PO4HB\|PROHB
	Cytomap	UCSC genome browser: 17q25
	Genomic location	chr17 :79801033-79818544
	Type of gene	protein-coding
	RefGenes	NM_000918.3,
	Ensembl id	ENSG00000185624
	Description	cellular thyroid hormone-binding proteincollagen prolyl 4-hydroxylase betaglutathione-insulin transhydrogenasep55procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), beta polypeptideprolyl 4-hydroxylase subunit betaprotein disu
	Modification date	20141207
dbXrefs	MIM : 176790
	HGNC : HGNC
	Ensembl : ENSG00000185624
	HPRD : 07181
	Vega : OTTHUMG00000150269
Protein	UniProt: P07237 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_P4HB
	BioGPS: 5034
	Gene Expression Atlas: ENSG00000185624
	The Human Protein Atlas: ENSG00000185624
Pathway	NCI Pathway Interaction Database: P4HB
	KEGG: P4HB
	REACTOME: P4HB
	ConsensusPathDB
	Pathway Commons: P4HB
Metabolism	MetaCyc: P4HB
	HUMANCyc: P4HB
Regulation	Ensembl's Regulation: ENSG00000185624
	miRBase: chr17 :79,801,033-79,818,544
	TargetScan: NM_000918
	cisRED: ENSG00000185624
Context	iHOP: P4HB
	cancer metabolism search in PubMed: P4HB
	UCL Cancer Institute: P4HB
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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Phenotypic Information for P4HB(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: P4HB
	Familial Cancer Database: P4HB

* 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 REACTOME_LIPOPROTEIN_METABOLISM

Others
OMIM	176790; gene.
Orphanet
Disease	KEGG Disease: P4HB
	MedGen: P4HB (Human Medical Genetics with Condition)
	ClinVar: P4HB
Phenotype	MGI: P4HB (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: P4HB

Mutations for P4HB

* 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	P4HB	chr17	79807097	79807117		chr17	79798818	79798838

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 P4HB 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
AW410007	RPS9	24	65	19	54704742	54705054	P4HB	66	545	17	79803074	79804852
DC413827	P4HB	2	295	17	79817205	79818437	PLEKHB2	291	519	2	131905344	131905573
BE878135	HELZ	1	228	17	65069444	65069671	P4HB	221	335	17	79801037	79801151
CN345438	P4HB	9	411	17	79817057	79818398	MAP4K4	410	622	2	102459069	102460700
BP290873	P4HB	1	209	17	79801408	79801616	UBE2E3	209	361	2	181846811	181846963

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=29)	Stat. for Synonymous SNVs (# total SNVs=22)

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
chr17:79818260-79818260	p.R30R	6
chr17:79803083-79803083	p.R461R	3
chr17:79803437-79803437	p.T453T	2
chr17:79803764-79803764	p.N387fs*118	2
chr17:79817119-79817119	p.R97H	2
chr17:79804462-79804462	p.R300H	2
chr17:79813041-79813041	p.D201H	2
chr17:79803104-79803104	p.V454V	1
chr17:79804920-79804920	p.I253S	1
chr17:79803557-79803557	p.T413T	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	6	1		3	1		2					6	4				4	6	1	7
# mutation	7	1		3	1		2					6	5				4	7	1	7
nonsynonymous SNV	4	1		3	1		1					4	4				3	4		5
synonymous SNV	3						1					2	1				1	3	1	2

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
chr17:79813047	p.L334L	2
chr17:79804359	p.D199H	2
chr17:79803437	p.E488Q	1
chr17:79804386	p.T413T	1
chr17:79801899	p.D180Y	1
chr17:79803439	p.E485Q	1
chr17:79804412	p.T335T	1
chr17:79801949	p.S168F	1
chr17:79813082	p.D480V	1
chr17:79803440	p.P135P	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 P4HB 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 P4HB

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


ANAPC11,ARHGDIA,OGFOD3,C17orf89,PRADC1,CALR,CCDC137, DUS1L,GAA,GPS1,MRPL12,P4HB,PCYT2,PPIB, PYCR1,SEC61A1,SLC25A10,SLC38A10,STRA13,ALYREF,TMEM104	C19orf10,CALR,CDK5,CNP,COMT,COPG1,CORO1B, CYB561D2,DPP3,DUS1L,FDPS,GMPPB,SLC52A2,GSS, HM13,LMAN2,MFSD7,NANS,P4HB,RRBP1,SLC39A7

AGR2,OGFOD3,C19orf10,CALR,CRELD2,ERO1L,GMPPA, HSP90B1,HSPA5,LGALS3BP,MANF,NUCB2,P4HB,PDIA3, PDIA3P1,PDIA4,PKM,PPIB,SEC61A1,SLC16A3,SRP68	ACOT7,ARPC1B,RTCB,CDCA3,CNDP2,CRCT1,DAP, ENTPD7,GMPPA,GRAMD2,P4HB,SEC13,SEC24A,SLC31A1, SLC35B1,SURF4,TFG,TSPO2,UNC5CL,WDR34,XPNPEP1

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 P4HB

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P07237; -.
Chemistry	ChEMBL	CHEMBL2364681; -.
Organism-specific databases	PharmGKB	PA32876; -.
Organism-specific databases	CTD	5034; -.

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
DB03615	prolyl 4-hydroxylase, beta polypeptide	experimental	Ribostamycin
DB00171	prolyl 4-hydroxylase, beta polypeptide	approved; nutraceutical	Adenosine triphosphate
DB00119	prolyl 4-hydroxylase, beta polypeptide	approved; nutraceutical	Pyruvic acid

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Cross referenced IDs for P4HB

* 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