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 KMO

Basic gene info.	Gene symbol	KMO
	Gene name	kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)
	Synonyms	dJ317G22.1
	Cytomap	UCSC genome browser: 1q42-q44
	Genomic location	chr1 :241695433-241758949
	Type of gene	protein-coding
	RefGenes	NM_003679.4,
	Ensembl id	ENSG00000117009
	Description	kynurenine 3-hydroxylasekynurenine 3-monooxygenase
	Modification date	20141207
dbXrefs	MIM : 603538
	HGNC : HGNC
	Ensembl : ENSG00000117009
	HPRD : 04642
	Vega : OTTHUMG00000039635
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_KMO
	BioGPS: 8564
	Gene Expression Atlas: ENSG00000117009
	The Human Protein Atlas: ENSG00000117009
Pathway	NCI Pathway Interaction Database: KMO
	KEGG: KMO
	REACTOME: KMO
	ConsensusPathDB
	Pathway Commons: KMO
Metabolism	MetaCyc: KMO
	HUMANCyc: KMO
Regulation	Ensembl's Regulation: ENSG00000117009
	miRBase: chr1 :241,695,433-241,758,949
	TargetScan: NM_003679
	cisRED: ENSG00000117009
Context	iHOP: KMO
	cancer metabolism search in PubMed: KMO
	UCL Cancer Institute: KMO
Assigned class in ccmGDB	C

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

Cancer Description
Cancer	CGAP: KMO
	Familial Cancer Database: KMO

* 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_TRYPTOPHAN_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

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

Mutations for KMO

* 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 KMO 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
AI819879	PSTPIP2	1	308	18	43563502	43563809	KMO	303	449	1	241720844	241720990
BG573396	KMO	1	146	1	241749339	241749484	MALAT1	141	571	11	65266714	65267143
AW451493	PSTPIP2	17	324	18	43563502	43563809	KMO	319	500	1	241720809	241720990

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	ns	ovary	pancre	prost	skin	stoma	thyro	urina
Total # sample	1	1		2		1	2		2								1
GAIN (# sample)	1	1		1					2								1
LOSS (# sample)				1		1	2

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=7

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=58)	Stat. for Synonymous SNVs (# total SNVs=14)

Stat. for Deletions (# total SNVs=1)	Stat. for Insertions (# total SNVs=2)

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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
chr1:241752099-241752099	p.A355A	6
chr1:241723977-241723977	p.Y125C	3
chr1:241755348-241755348	p.R452C	3
chr1:241728295-241728295	p.M208I	3
chr1:241753390-241753390	p.S392L	3
chr1:241752119-241752119	p.Y362C	2
chr1:241725561-241725561	p.R182C	2
chr1:241695795-241695795	p.G17G	2
chr1:241753371-241753371	p.L386I	2
chr1:241755337-241755337	p.R448Q	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=8

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	1	1		17			1		1			9	5	3			10	3		12
# mutation	1	1		15			1		1			8	5	3			10	3		12
nonsynonymous SNV	1	1		12			1					5	4	2			8	1		11
synonymous SNV				3					1			3	1	1			2	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
chr1:241752099	p.A355A	6
chr1:241753390	p.S392L	3
chr1:241714340	p.S392P	2
chr1:241725561	p.L272P	2
chr1:241731805	p.R182C	2
chr1:241753371	p.L90V	2
chr1:241753389	p.A355G	2
chr1:241714300	p.S103F	2
chr1:241752098	p.L386I	2
chr1:241731804	p.V148V	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 KMO 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 KMO

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


ABCC11,C12orf74,CLCA2,CYP4Z2P,ERBB2,ETFA,GGCT, ITGB6,KMO,KYNU,LINC01105,MPHOSPH6,PSMD5,SLC31A1, SPINK8,SRD5A3,TC2N,TMEM62,TMEM86A,TP53INP2,TRPV6	AFMID,AKR1B15,ALDH3B2,DHRS2,GGT1,GGTLC2,HIST1H2AE, HIST1H2BG,HIST1H3D,HIST1H4H,HMGCS2,HRASLS2,KMO,KYNU, PPEF1,RASGRF1,SERHL2,SERHL,SPINK8,UGT2B10,UGT2B28

APBB1IP,BTK,SCIMP,CD53,DOK2,DOK3,FGR, HCST,HK3,ITGB2,KMO,LAPTM5,LILRB1,LILRB4, LSP1,NCKAP1L,PARVG,SPI1,STX11,TFEC,TNFAIP8L2	ARHGAP15,ARHGAP25,ARHGDIB,BTK,BTLA,CCL19,CD53, CD72,CSTA,DAPP1,GAPT,HLA-DOB,ICOS,KMO, LAT2,LY86,PTPRC,RGS19,RHOH,SERPINB9,TNFAIP8

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 KMO

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
DB00130	kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)	approved; nutraceutical; investigational	L-Glutamine
DB00160	kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)	approved; nutraceutical	L-Alanine
DB00150	kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)	approved; nutraceutical	L-Tryptophan

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Cross referenced IDs for KMO

* 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