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 PRODH

Basic gene info.	Gene symbol	PRODH
	Gene name	proline dehydrogenase (oxidase) 1
	Synonyms	HSPOX2\|PIG6\|POX\|PRODH1\|PRODH2\|TP53I6
	Cytomap	UCSC genome browser: 22q11.21
	Genomic location	chr22 :18900286-18924066
	Type of gene	protein-coding
	RefGenes	NM_001195226.1, NM_016335.4,
	Ensembl id	ENSG00000100033
	Description	p53-induced gene 6 proteinproline dehydrogenase 1, mitochondrialproline oxidase 2proline oxidase, mitochondrialtumor protein p53 inducible protein 6
	Modification date	20141211
dbXrefs	MIM : 606810
	HGNC : HGNC
	Ensembl : ENSG00000100033
	HPRD : 08433
	Vega : OTTHUMG00000150163
Protein	UniProt: O43272 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PRODH
	BioGPS: 5625
	Gene Expression Atlas: ENSG00000100033
	The Human Protein Atlas: ENSG00000100033
Pathway	NCI Pathway Interaction Database: PRODH
	KEGG: PRODH
	REACTOME: PRODH
	ConsensusPathDB
	Pathway Commons: PRODH
Metabolism	MetaCyc: PRODH
	HUMANCyc: PRODH
Regulation	Ensembl's Regulation: ENSG00000100033
	miRBase: chr22 :18,900,286-18,924,066
	TargetScan: NM_001195226
	cisRED: ENSG00000100033
Context	iHOP: PRODH
	cancer metabolism search in PubMed: PRODH
	UCL Cancer Institute: PRODH
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of PRODH in cancer cell metabolism	1. Liu W, Le A, Hancock C, Lane AN, Dang CV, et al. (2012) Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proceedings of the National Academy of Sciences 109: 8983-8988. go to article

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

Cancer Description
Cancer	CGAP: PRODH
	Familial Cancer Database: PRODH

* 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_ARGININE_AND_PROLINE_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM	181500; phenotype. 181500; phenotype. 239500; phenotype. 239500; phenotype. 600850; phenotype. 600850; phenotype. 606810; gene. 606810; gene.
Orphanet	3140; Schizophrenia. 3140; Schizophrenia. 419; Hyperprolinemia type 1. 419; Hyperprolinemia type 1.
Disease	KEGG Disease: PRODH
	MedGen: PRODH (Human Medical Genetics with Condition)
	ClinVar: PRODH
Phenotype	MGI: PRODH (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PRODH

Mutations for PRODH

* 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 PRODH 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

AI497670

USP11

287

47107462

47107727

PRODH

282

345

18913475

18913538

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=47)	Stat. for Synonymous SNVs (# total SNVs=10)

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
chr22:18912670-18912670	p.F187F	3
chr22:18905964-18905964	p.R431H	3
chr22:18923745-18923745	p.P19Q	2
chr22:18907255-18907255	p.M356I	2
chr22:18910355-18910355	p.T275N	2
chr22:18905833-18905833	p.H475Y	2
chr22:18908910-18908910	p.S319I	2
chr22:18910675-18910675	p.G229C	2
chr22:18913208-18913208	p.D170E	1
chr22:18907071-18907071	p.E382K	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	3		1	4	1		1	2	1			4	1				4			10
# mutation	3		1	4	1		1	2	1			4	1				4			14
nonsynonymous SNV	2		1	4	1		1	2	1			3	1				1			11
synonymous SNV	1											1					3			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
chr22:18918708	p.L93L	2
chr22:18912654	p.H367Y,PRODH	1
chr22:18904467	p.R109C,PRODH	1
chr22:18907273	p.N363N,PRODH	1
chr22:18912670	p.A95T,PRODH	1
chr22:18904488	p.E348E,PRODH	1
chr22:18908902	p.R90H,PRODH	1
chr22:18912699	p.R345H,PRODH	1
chr22:18905833	p.G85S,PRODH	1
chr22:18909852	p.A344A,PRODH	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 PRODH 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 PRODH

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,APOA2,APOA4,APOC3,C8A,C9,CREB3L3, CRP,F2,FABP1,FGF23,HP,ITIH1,MT1B, PLG,PRODH2,SERPINA7,SERPINC1,SLC17A2,SULT2A1,TM4SF5	NA,NA,NA,NA,NA,NA,NA, NA,NA,NA,NA,NA,NA,NA, NA,NA,NA,NA,NA,NA,NA

ARMC3,ATP6V1B1,LRRC71,CDC20B,FOXN4,GH2,HAPLN4, KCNH3,KCNJ16,KCNJ4,KCNQ2,KIF1A,LHFPL5,LPPR3, MOS,NECAB2,PAX4,PRODH2,RD3,TEKT1,TMEM190	NPSR1-AS1,AQP5,C1orf146,C4orf51,C5orf47,GGNBP1,LHX3, LOC285627,MSH4,PDCL2,PRODH2,SERPINB7,SNORA71A,SNORA80A, SNORD15B,SPRR1A,SPRR1B,SYCP2L,CATSPERD,TRIM69,ZNF705A

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 PRODH

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA33801; -.
Organism-specific databases	PharmGKB	PA33801; -.
Organism-specific databases	CTD	5625; -.
Organism-specific databases	CTD	5625; -.

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
DB00172	proline dehydrogenase (oxidase) 1	approved; nutraceutical	L-Proline

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Cross referenced IDs for PRODH

* 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