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 DAO

Basic gene info.	Gene symbol	DAO
	Gene name	D-amino-acid oxidase
	Synonyms	DAAO\|DAMOX\|OXDA
	Cytomap	UCSC genome browser: 12q24
	Genomic location	chr12 :109273856-109294710
	Type of gene	protein-coding
	RefGenes	NM_001917.4,
	Ensembl id	ENSG00000110887
	Description	D-amino acid oxidase
	Modification date	20141207
dbXrefs	MIM : 124050
	HGNC : HGNC
	Ensembl : ENSG00000110887
	HPRD : 15917
	Vega : OTTHUMG00000169360
Protein	UniProt: P14920 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_DAO
	BioGPS: 1610
	Gene Expression Atlas: ENSG00000110887
	The Human Protein Atlas: ENSG00000110887
Pathway	NCI Pathway Interaction Database: DAO
	KEGG: DAO
	REACTOME: DAO
	ConsensusPathDB
	Pathway Commons: DAO
Metabolism	MetaCyc: DAO
	HUMANCyc: DAO
Regulation	Ensembl's Regulation: ENSG00000110887
	miRBase: chr12 :109,273,856-109,294,710
	TargetScan: NM_001917
	cisRED: ENSG00000110887
Context	iHOP: DAO
	cancer metabolism search in PubMed: DAO
	UCL Cancer Institute: DAO
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of DAO in cancer cell metabolism	1. Fang J, Nakamura H, Iyer AK (2007) Tumor-targeted induction of oxystress for cancer therapy. J Drug Target 15: 475-486. doi: 10.1080/10611860701498286. go to article 2. El Sayed SM, El-Magd RM, Shishido Y, Chung SP, Diem TH, et al. (2012) 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects. J Bioenerg Biomembr 44: 61-79. doi: 10.1007/s10863-012-9409-4. go to article 3. El Sayed SM, El-Magd RM, Shishido Y, Yorita K, Chung SP, et al. (2012) D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects. J Bioenerg Biomembr 44: 513-523. doi: 10.1007/s10863-012-9455-y. go to article 4. El Sayed SM, Abou El-Magd RM, Shishido Y, Chung SP, Sakai T, et al. (2012) D-amino acid oxidase gene therapy sensitizes glioma cells to the antiglycolytic effect of 3-bromopyruvate. Cancer Gene Ther 19: 1-18. doi: 10.1038/cgt.2011.59. go to article 5. Fang J, Seki T, Maeda H (2009) Therapeutic strategies by modulating oxygen stress in cancer and inflammation. Adv Drug Deliv Rev 61: 290-302. doi: 10.1016/j.addr.2009.02.005. go to article

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

Cancer Description
Cancer	CGAP: DAO
	Familial Cancer Database: DAO

* 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_GLYCINE_SERINE_AND_THREONINE_METABOLISM KEGG_ARGININE_AND_PROLINE_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM	124050; gene.
Orphanet	803; Amyotrophic lateral sclerosis.
Disease	KEGG Disease: DAO
	MedGen: DAO (Human Medical Genetics with Condition)
	ClinVar: DAO
Phenotype	MGI: DAO (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: DAO

Mutations for DAO

* 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 DAO 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
X13227	MT1G	1	81	16	56701895	56701975	DAO	76	1629	12	109273885	109294697
AX786389	MT1G	1	81	16	56701895	56701975	DAO	76	1629	12	109273885	109294697

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=5

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=52)	Stat. for Synonymous SNVs (# total SNVs=14)

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
chr12:109278816-109278816	p.G12R	3
chr12:109293186-109293186	p.R283W	3
chr12:109293196-109293196	p.R286H	3
chr12:109288048-109288048	p.E173K	3
chr12:109283320-109283320	p.G129C	3
chr12:109288126-109288126	p.R199W	2
chr12:109292540-109292540	p.E261K	2
chr12:109293195-109293195	p.R286C	2
chr12:109283296-109283296	p.E121*	2
chr12:109293207-109293207	p.R290W	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	1	5	4		1		1			5	1	1		2	9	6		8
# mutation		2	1	6	4		1		1			6	1	1		2	11	6		10
nonsynonymous SNV			1	6	4				1			3	1			1	9	6		9
synonymous SNV		2					1					3		1		1	2			1

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
chr12:109293196	p.R286H	2
chr12:109293207	p.R290W	2
chr12:109293228	p.R297C	2
chr12:109286790	p.R162Q	2
chr12:109288048	p.E173K	2
chr12:109278864	p.A36T	1
chr12:109293195	p.A188A	1
chr12:109283320	p.T45T	1
chr12:109294270	p.R199W	1
chr12:109290797	p.D46N	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 DAO 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 DAO

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


AHSG,APOA1,APOA2,APOC3,APOC4,ASGR2,DAO, F2,HAMP,HRG,ITIH1,ITIH3,KNG1,LEAP2, PLG,SERPINC1,SLC17A2,SLC22A7,SLC2A2,SPP2,SULT2A1	ADRA1D,BEX1,PRR35,CACNA1H,CHRNA9,COL2A1,CST9, DAO,DEFB4A,FAM135B,FCRLB,GLDC,HBQ1,LRTM2, SLC6A4,SLIT1,SPDYC,TCL1B,TTLL8,WFDC11,ZNF479

AQP8,C1orf106,CDHR5,CTXN2,DAO,DIO3OS,DIRAS2, ENAM,FAM132A,G6PC,KCTD4,LPGAT1,LRRN2,PCDHA10, PCDHGB4,PHLPP2,PTPN14,SCARNA21,SLC16A4,SOX3,TBPL2	ANXA11,ATP6V0D1,CA4,CLIC5,CORO1B,DAO,IFI27, LRRC56,MYD88,OAS1,PLAC8,PPP1R14D,RAB4B,RALY, SH3BP1,TDRD7,TEX11,TJP3,TMEM54,TRIM31,TWF2

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 DAO

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P14920; -.
Chemistry	ChEMBL	CHEMBL5485; -.
Organism-specific databases	PharmGKB	PA27139; -.
Organism-specific databases	CTD	1610; -.

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
DB02838	D-amino-acid oxidase	experimental	3,4-Dihydro-2h-Pyrrolium-5-Carboxylate
DB02988	D-amino-acid oxidase	experimental	Imino-Tryptophan
DB03147	D-amino-acid oxidase	experimental	Flavin-Adenine Dinucleotide
DB03225	D-amino-acid oxidase	experimental	D-Tryptophan
DB03531	D-amino-acid oxidase	experimental	Flavin-Adenine Dinucleotide-N5-Isobutyl Ketone
DB03793	D-amino-acid oxidase	experimental	Benzoic Acid
DB04166	D-amino-acid oxidase	experimental	2-Aminobenzoic Acid
DB07979	D-amino-acid oxidase	experimental	(2E)-3-(3,4-DIHYDROXYPHENYL)-2-IMINOPROPANOIC ACID
DB00145	D-amino-acid oxidase	approved; nutraceutical	Glycine
DB00160	D-amino-acid oxidase	approved; nutraceutical	L-Alanine

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Cross referenced IDs for DAO

* 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