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 AKR1B1

Basic gene info.	Gene symbol	AKR1B1
	Gene name	aldo-keto reductase family 1, member B1 (aldose reductase)
	Synonyms	ADR\|ALDR1\|ALR2\|AR
	Cytomap	UCSC genome browser: 7q35
	Genomic location	chr7 :134127106-134143888
	Type of gene	protein-coding
	RefGenes	NM_001628.2,
	Ensembl id	ENSG00000085662
	Description	Lii5-2 CTCL tumor antigenaldehyde reductase 1aldo-keto reductase family 1 member B1aldose reductaselow Km aldose reductase
	Modification date	20141207
dbXrefs	MIM : 103880
	HGNC : HGNC
	Ensembl : ENSG00000085662
	HPRD : 00071
	Vega : OTTHUMG00000155322
Protein	UniProt: P15121 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_AKR1B1
	BioGPS: 231
	Gene Expression Atlas: ENSG00000085662
	The Human Protein Atlas: ENSG00000085662
Pathway	NCI Pathway Interaction Database: AKR1B1
	KEGG: AKR1B1
	REACTOME: AKR1B1
	ConsensusPathDB
	Pathway Commons: AKR1B1
Metabolism	MetaCyc: AKR1B1
	HUMANCyc: AKR1B1
Regulation	Ensembl's Regulation: ENSG00000085662
	miRBase: chr7 :134,127,106-134,143,888
	TargetScan: NM_001628
	cisRED: ENSG00000085662
Context	iHOP: AKR1B1
	cancer metabolism search in PubMed: AKR1B1
	UCL Cancer Institute: AKR1B1
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of AKR1B1 in cancer cell metabolism	1. Uzozie A, Nanni P, Staiano T, Grossmann J, Barkow-Oesterreicher S, et al. (2014) Sorbitol dehydrogenase overexpression and other aspects of dysregulated protein expression in human precancerous colorectal neoplasms: a quantitative proteomics study. Mol Cell Proteomics 13: 1198-1218. doi: 10.1074/mcp.M113.035105. pmid: 4014279 go to article 2. Balendiran GK, Martin HJ, El-Hawari Y, Maser E (2009) Cancer biomarker AKR1B10 and carbonyl metabolism. Chem Biol Interact 178: 134-137. doi: 10.1016/j.cbi.2008.10.044. go to article

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Phenotypic Information for AKR1B1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: AKR1B1
	Familial Cancer Database: AKR1B1

* 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_FRUCTOSE_AND_MANNOSE_METABOLISM KEGG_GALACTOSE_METABOLISM KEGG_GLYCEROLIPID_METABOLISM KEGG_PYRUVATE_METABOLISM REACTOME_METABOLISM_OF_STEROID_HORMONES_AND_VITAMINS_A_AND_D REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	103880; gene.
Orphanet
Disease	KEGG Disease: AKR1B1
	MedGen: AKR1B1 (Human Medical Genetics with Condition)
	ClinVar: AKR1B1
Phenotype	MGI: AKR1B1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: AKR1B1

Mutations for AKR1B1

* 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 AKR1B1 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
BG009392	TBCD	61	156	17	80790096	80790191	AKR1B1	148	340	7	134134452	134135632
AV708454	KDM4A	1	92	1	44166118	44166263	AKR1B1	87	391	7	134134330	134135623
AV701562	PHF15	1	86	5	133860064	133871576	AKR1B1	81	649	7	134127108	134132119
AI654627	AKR1B1	7	238	7	134127108	134127339	PPP1R21	228	501	2	48718191	48725693
AV705293	AKR1B1	48	688	7	134130004	134135656	ITK	672	695	5	156679776	156679822

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=21)	Stat. for Synonymous SNVs (# total SNVs=10)

Stat. for Deletions (# total SNVs=1)	Stat. for Insertions (# total SNVs=0)
	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
chr7:134134532-134134532	p.F123F	5
chr7:134133183-134133183	p.I205I	3
chr7:134132069-134132069	p.R269H	2
chr7:134132761-134132761	p.A238T	2
chr7:134134517-134134517	p.S128S	2
chr7:134132815-134132815	p.?	1
chr7:134143774-134143774	p.P14R	1
chr7:134132056-134132056	p.N273K	1
chr7:134136364-134136364	p.R70C	1
chr7:134133142-134133142	p.P219L	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=6

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			9			2		2	1		6	1	5			9	7
# mutation	1			7			2		2	1		6	1	5			4	9
nonsynonymous SNV	1			5			2		1			5	1	4			1	6
synonymous SNV				2					1	1		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
chr7:134134532	p.F123F	6
chr7:134132069	p.R269H	3
chr7:134132761	p.A238T	2
chr7:134133231	p.N257D	1
chr7:134135631	p.P113L	1
chr7:134132059	p.F252L	1
chr7:134143812	p.L109L	1
chr7:134133770	p.R251Q	1
chr7:134135632	p.Y104C	1
chr7:134133802	p.K86K	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 AKR1B1 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 AKR1B1

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


AKR1B10,AKR1C1,AKR1C3,ALDH3A1,BCL2L10,C10orf99,FOXE1, GAGE12J,GAGE2B,GAGE8,GPX2,IQCF2,KRT13,KRT74, LOC285629,NKX2-4,RBMXL2,UGT1A5,VCX,VCX3A,VCY	ADH7,AKR1B10,ALDH3A1,C10orf99,CAPNS2,CYP4F3,GJB6, KRT13,KRT4,KRT6A,KRT78,KRTDAP,SOX2,SPRR1A, SPRR1B,SPRR2A,SPRR2D,SPRR3,TMPRSS11D,UGT1A7,UPK1B

AKR1B10,AKR1B15,BTNL3,C11orf86,MIEN1,AXDND1,DHRS9, ERBB2,KRT20,MALL,MMP28,MSL1,PPP1R1B,RAPGEFL1, TCAP,TMEM54,TMEM82,TSPAN1,UGT1A1,UGT1A8,WIPF2	ABCD3,AKR1B10,AP1AR,CROT,CRYL1,CTAGE5,ETFDH, FAM73B,FLVCR2,HADHB,KALRN,NCOA4,OCIAD2,PDXP, PRR13,RBKS,RRAS2,STK17B,TMEM139,SLC35G1,UGT1A9

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 AKR1B1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P15121; -.
Chemistry	ChEMBL	CHEMBL1900; -.
Chemistry	GuidetoPHARMACOLOGY	2768; -.
Organism-specific databases	PharmGKB	PA24675; -.
Organism-specific databases	CTD	231; -.

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
DB00157	aldo-keto reductase family 1, member B1 (aldose reductase)	approved; nutraceutical	NADH
DB00605	aldo-keto reductase family 1, member B1 (aldose reductase)	approved	Sulindac
DB01689	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Inhibitor Idd 384
DB02007	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Alpha-D-Glucose-6-Phosphate
DB02020	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Alrestatin
DB02021	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Fidarestat
DB02101	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Fidarestat(Stereoisomer)
DB02132	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	[3-(4-Bromo-2-Fluoro-Benzyl)-7-Chloro-2,4-Dioxo-3,4-Dihydro-2h-Quinazolin-1-Yl]-Acetic Acid
DB02383	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Tolrestat
DB02518	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	N-Acetylalanine
DB02712	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Sorbinil
DB02834	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	IDD552
DB02994	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Hydroxydimethylarsine Oxide
DB03461	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	2'-Monophosphoadenosine 5'-Diphosphoribose
DB04272	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	Citric Acid
DB07028	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	(2-{[(4-BROMO-2-FLUOROBENZYL)AMINO]CARBONYL}-5-CHLOROPHENOXY)ACETIC ACID
DB07030	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	(5-CHLORO-2-{[(3-NITROBENZYL)AMINO]CARBONYL}PHENOXY)ACETIC ACID
DB07063	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	{3-[(4,5,7-TRIFLUORO-1,3-BENZOTHIAZOL-2-YL)METHYL]-1H-INDOL-1-YL}ACETIC ACID
DB07093	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	{3-[(5-CHLORO-1,3-BENZOTHIAZOL-2-YL)METHYL]-2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL}ACETIC ACID
DB07139	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	3-[5-(3-nitrophenyl)thiophen-2-yl]propanoic acid
DB07187	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	6-[(5-CHLORO-3-METHYL-1-BENZOFURAN-2-YL)SULFONYL]PYRIDAZIN-3(2H)-ONE
DB07450	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	2[4-BROMO-2-FLUOROPHENYL)METHYL]-6-FLUOROSPIRO[ISOQUINOLINE-4-(1H),3'-PYRROLIDINE]-1,2',3,5'(2H)-TETRONE
DB07498	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	4-[3-(3-NITROPHENYL)-1,2,4-OXADIAZOL-5-YL]BUTANOIC ACID
DB07999	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	{4-[(CARBOXYMETHOXY)CARBONYL]-3,3-DIOXIDO-1-OXONAPHTHO[1,2-D]ISOTHIAZOL-2(1H)-YL}ACETIC ACID
DB08000	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	2-(CARBOXYMETHYL)-1-OXO-1,2-DIHYDRONAPHTHO[1,2-D]ISOTHIAZOLE-4-CARBOXYLIC ACID 3,3-DIOXIDE
DB08084	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	IDD594
DB08098	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	{[5-(5-NITRO-2-FURYL)-1,3,4-OXADIAZOL-2-YL]THIO}ACETIC ACID
DB08449	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	2-(3-((4,5,7-trifluorobenzo[d]thiazol-2-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)acetic acid
DB08772	aldo-keto reductase family 1, member B1 (aldose reductase)	experimental	3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE ACETIC ACID

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Cross referenced IDs for AKR1B1

* 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