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 DBH

Basic gene info.	Gene symbol	DBH
	Gene name	dopamine beta-hydroxylase (dopamine beta-monooxygenase)
	Synonyms	DBM
	Cytomap	UCSC genome browser: 9q34
	Genomic location	chr9 :136501484-136524466
	Type of gene	protein-coding
	RefGenes	NM_000787.3,
	Ensembl id	ENSG00000123454
	Description	dopamine beta-hydroxylase
	Modification date	20141222
dbXrefs	MIM : 609312
	HGNC : HGNC
	Ensembl : ENSG00000123454
	HPRD : 01963
	Vega : OTTHUMG00000020878
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_DBH
	BioGPS: 1621
	Gene Expression Atlas: ENSG00000123454
	The Human Protein Atlas: ENSG00000123454
Pathway	NCI Pathway Interaction Database: DBH
	KEGG: DBH
	REACTOME: DBH
	ConsensusPathDB
	Pathway Commons: DBH
Metabolism	MetaCyc: DBH
	HUMANCyc: DBH
Regulation	Ensembl's Regulation: ENSG00000123454
	miRBase: chr9 :136,501,484-136,524,466
	TargetScan: NM_000787
	cisRED: ENSG00000123454
Context	iHOP: DBH
	cancer metabolism search in PubMed: DBH
	UCL Cancer Institute: DBH
Assigned class in ccmGDB	C

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

Cancer Description
Cancer	CGAP: DBH
	Familial Cancer Database: DBH

* 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_TYROSINE_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM
Orphanet
Disease	KEGG Disease: DBH
	MedGen: DBH (Human Medical Genetics with Condition)
	ClinVar: DBH
Phenotype	MGI: DBH (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: DBH

Mutations for DBH

* 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
ovary	DBH	chr9	136508337	136508357	DBH	chr9	136508545	136508565
ovary	DBH	chr9	136521852	136521872	MAPK8IP3	chr16	1820216	1820236

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 DBH 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

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=63)	Stat. for Synonymous SNVs (# total SNVs=35)

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
chr9:136508616-136508616	p.V276I	6
chr9:136517406-136517406	p.P458P	3
chr9:136518097-136518097	p.T470T	3
chr9:136508597-136508597	p.C269C	3
chr9:136508598-136508598	p.A270T	3
chr9:136505114-136505114	p.E162E	3
chr9:136523486-136523486	p.E591K	2
chr9:136512976-136512976	p.D345N	2
chr9:136501721-136501721	p.L76L	2
chr9:136512992-136512992	p.R350H	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=3

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	3	1	13	5		4		2			7	2	5	1		18	9		12
# mutation	2	3	1	12	4		4		2			7	2	5	1		17	10		15
nonsynonymous SNV	2	2		6	1		3		2			5	2	4	1		9	4		9
synonymous SNV		1	1	6	3		1					2		1			8	6		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
chr9:136508583	p.C269C	2
chr9:136516782	p.L76L	2
chr9:136508597	p.G281R	2
chr9:136501721	p.I406I	2
chr9:136508631	p.E265K	2
chr9:136517375	p.R359C	1
chr9:136501635	p.F558L	1
chr9:136507542	p.F74F	1
chr9:136508675	p.I183M	1
chr9:136501814	p.D274N	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 DBH 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 DBH

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,ASGR2,C3P1,C8A,C9, CREB3L3,CRP,DBH,F2,FABP1,FGF23,HP, ITIH1,ITIH3,MT1B,SERPINA7,SLC17A2,SULT2A1,TM4SF5	ACSM2A,ACSM2B,AMN,APOC3,APOL4,TBATA,CHGA, CHGB,CPO,DBH,NDRG4,NTSR2,ORM1,ORM2, PDZD7,PHOX2B,SLC18A1,SNORA14A,ST8SIA3,TH,TTC36

AMBN,CACNA1S,CALML3,CST5,DBH,ENTPD3,FGF8, KLK14,KRT31,LIPM,MUCL1,NELL2,RPTN,S100A3, SERPINI1,SEZ6L,SNAP91,SPAG6,SST,TCHHL1,TULP2	ATM,C3orf62,CDYL2,CNTRL,DBH,EML6,GRAPL, KCNMB3,KDM2B,LOC100131691,LTB4R,LTB4R2,NFATC2,QSOX2, RBM6,RPL32P3,SLC4A8,THRAP3,TTN,USP49,ZNF335

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 DBH

Cross-referenced pharmacological DB IDs from Uniprot

DB Category

DB Name

DB's ID and Url link

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
DB00126	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved; nutraceutical	Vitamin C
DB00822	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved	Disulfiram
DB00988	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved	Dopamine
DB00184	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved	Nicotine
DB00135	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved; nutraceutical	L-Tyrosine
DB00360	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved; investigational	Tetrahydrobiopterin
DB00368	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved	Norepinephrine
DB01235	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved	Levodopa
DB01156	dopamine beta-hydroxylase (dopamine beta-monooxygenase)	approved	Bupropion

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Cross referenced IDs for DBH

* 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