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 NAT2

Basic gene info.	Gene symbol	NAT2
	Gene name	N-acetyltransferase 2 (arylamine N-acetyltransferase)
	Synonyms	AAC2\|NAT-2\|PNAT
	Cytomap	UCSC genome browser: 8p22
	Genomic location	chr8 :18248754-18258723
	Type of gene	protein-coding
	RefGenes	NM_000015.2,
	Ensembl id	ENSG00000156006
	Description	N-acetyltransferase type 2arylamide acetylase 2arylamine N-acetyltransferase 2
	Modification date	20141211
dbXrefs	MIM : 612182
	HGNC : HGNC
	Ensembl : ENSG00000156006
	HPRD : 02000
	Vega : OTTHUMG00000130826
Protein	UniProt: P11245 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_NAT2
	BioGPS: 10
	Gene Expression Atlas: ENSG00000156006
	The Human Protein Atlas: ENSG00000156006
Pathway	NCI Pathway Interaction Database: NAT2
	KEGG: NAT2
	REACTOME: NAT2
	ConsensusPathDB
	Pathway Commons: NAT2
Metabolism	MetaCyc: NAT2
	HUMANCyc: NAT2
Regulation	Ensembl's Regulation: ENSG00000156006
	miRBase: chr8 :18,248,754-18,258,723
	TargetScan: NM_000015
	cisRED: ENSG00000156006
Context	iHOP: NAT2
	cancer metabolism search in PubMed: NAT2
	UCL Cancer Institute: NAT2
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of NAT2 in cancer cell metabolism	1. Matejcic M, Vogelsang M, Wang Y, Parker M (2015) NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study. BMC cancer 15: 150. go to article

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Phenotypic Information for NAT2(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: NAT2
	Familial Cancer Database: NAT2

* 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_DRUG_METABOLISM_OTHER_ENZYMES

Others
OMIM	243400; phenotype. 243400; phenotype. 612182; gene. 612182; gene.
Orphanet	240887; Isoniazid toxicity. 240887; Isoniazid toxicity. 240975; Susceptibility to adverse reaction due to isoniazide treatment. 240975; Susceptibility to adverse reaction due to isoniazide treatment.
Disease	KEGG Disease: NAT2
	MedGen: NAT2 (Human Medical Genetics with Condition)
	ClinVar: NAT2
Phenotype	MGI: NAT2 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: NAT2

Mutations for NAT2

* 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	NAT2	chr8	18254952	18254972		chr8	18244772	18244792

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 NAT2 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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=25)	Stat. for Synonymous SNVs (# total SNVs=9)

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
chr8:18258334-18258334	p.S274F	3
chr8:18257858-18257858	p.D115D	3
chr8:18257539-18257539	p.R9I	3
chr8:18257994-18257994	p.L161L	2
chr8:18257673-18257673	p.A54T	2
chr8:18258186-18258186	p.L225L	2
chr8:18257864-18257864	p.R117R	2
chr8:18257721-18257721	p.Q70*	2
chr8:18258245-18258245	p.F244L	2
chr8:18258273-18258273	p.E254K	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				7	1				2			4	1	2			10	6		3
# mutation				5	2				2			4	1	2			10	6		3
nonsynonymous SNV				2	2				2			2	1	1			5	4		3
synonymous SNV				3								2		1			5	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
chr8:18257539	p.R9K	3
chr8:18257673	p.D115D	2
chr8:18258334	p.S274F	2
chr8:18257858	p.L21F	2
chr8:18258186	p.A54T	2
chr8:18257576	p.L225L	2
chr8:18258288	p.E260G	1
chr8:18258036	p.E264E	1
chr8:18258292	p.R117W	1
chr8:18257712	p.Q133H	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 NAT2 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 NAT2

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


ASAH1,LINC00589,CCDC60,CCDC74A,CYP4A11,DCST1,FAM120AOS, FAM181B,FDXACB1,MAP10,KRT40,KRTAP1-3,KRTAP3-2,KRTAP3-3, MBOAT2,MIPOL1,NAT2,PRCP,RBM11,ZNRF3,ZPLD1	ACSL3,ADAM2,ALOX15B,APOD,DHRS2,ENPP3,GUSB, HAAO,IDI1,NANOG,NAT2,PNLIPRP3,PPEF1,RNASE12, SERHL2,SERHL,SLC15A1,SPINK8,SULT1C3,UGT2B10,UGT2B11

C10orf99,METTL25,AXDND1,CCDC25,CNOT7,DMTN,EPHX2, ERICH1,FABP1,FBXO25,FDFT1,GGT6,INTS10,INTS9, LONRF1,MCPH1,NAT1,NAT2,PEX11A,PPP1R14D,TTC38	ABCD3,BPNT1,ABRACL,CRYL1,CTAGE5,ETFDH,FDX1, GNG12,MGST3,NAT2,NRAS,SLC51B,PAFAH2,SLC25A20, SLC35D2,SLC35F5,SNX14,SPPL2A,TGFA,TMEM139,VTA1

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 NAT2

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	ChEMBL	CHEMBL2194; -.
Chemistry	ChEMBL	CHEMBL2194; -.
Organism-specific databases	PharmGKB	PA18; -.
Organism-specific databases	PharmGKB	PA18; -.
Organism-specific databases	CTD	10; -.
Organism-specific databases	CTD	10; -.

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
DB01248	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved; investigational	Docetaxel
DB01041	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved; withdrawn; investigational	Thalidomide
DB00250	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved; investigational	Dapsone
DB01068	N-acetyltransferase 2 (arylamine N-acetyltransferase)	illicit; approved	Clonazepam
DB00951	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Isoniazid
DB00259	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Sulfanilamide
DB00945	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Acetylsalicylic acid
DB00277	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Theophylline
DB00898	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Ethanol
DB01412	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Theobromine
DB00286	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Conjugated Estrogens
DB00201	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Caffeine
DB00811	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Ribavirin
DB00514	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Dextromethorphan
DB01582	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Sulfamethazine
DB00563	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Methotrexate
DB00795	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Sulfasalazine
DB01015	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Sulfamethoxazole
DB01035	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Procainamide
DB01275	N-acetyltransferase 2 (arylamine N-acetyltransferase)	approved	Hydralazine

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Cross referenced IDs for NAT2

* 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