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 AKR1B10

Basic gene info.	Gene symbol	AKR1B10
	Gene name	aldo-keto reductase family 1, member B10 (aldose reductase)
	Synonyms	AKR1B11\|AKR1B12\|ALDRLn\|ARL-1\|ARL1\|HIS\|HSI
	Cytomap	UCSC genome browser: 7q33
	Genomic location	chr7 :134212343-134226166
	Type of gene	protein-coding
	RefGenes	NM_020299.4,
	Ensembl id	ENSG00000198074
	Description	ARPSI reductasealdo-keto reductase family 1 member B10aldo-keto reductase family 1, member B11 (aldose reductase-like)aldose reductase-like 1aldose reductase-like peptidealdose reductase-related proteinhARPsmall intestine reductase
	Modification date	20141207
dbXrefs	MIM : 604707
	HGNC : HGNC
	Ensembl : ENSG00000198074
	HPRD : 05271
	Vega : OTTHUMG00000155356
Protein	UniProt: O60218 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_AKR1B10
	BioGPS: 57016
	Gene Expression Atlas: ENSG00000198074
	The Human Protein Atlas: ENSG00000198074
Pathway	NCI Pathway Interaction Database: AKR1B10
	KEGG: AKR1B10
	REACTOME: AKR1B10
	ConsensusPathDB
	Pathway Commons: AKR1B10
Metabolism	MetaCyc: AKR1B10
	HUMANCyc: AKR1B10
Regulation	Ensembl's Regulation: ENSG00000198074
	miRBase: chr7 :134,212,343-134,226,166
	TargetScan: NM_020299
	cisRED: ENSG00000198074
Context	iHOP: AKR1B10
	cancer metabolism search in PubMed: AKR1B10
	UCL Cancer Institute: AKR1B10
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of AKR1B10 in cancer cell metabolism	1. Ruiz FX, Porte S, Pares X, Farres J (2012) Biological role of aldo-keto reductases in retinoic Acid biosynthesis and signaling. Front Pharmacol 3: 58. doi: 10.3389/fphar.2012.00058. pmid: 3328219. 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 3. Zhang W, Li H, Yang Y, Liao J, Yang GY (2014) Knockdown or inhibition of aldo-keto reductase 1B10 inhibits pancreatic carcinoma growth via modulating Kras-E-cadherin pathway. Cancer Lett 355: 273-280. doi: 10.1016/j.canlet.2014.09.031. pmid: 4462172. go to article 4. Nishinaka T, Miura T, Sakou M, Hidaka C, Sasaoka C, et al. (2015) Down-regulation of aldo-keto reductase AKR1B10 gene expression by a phorbol ester via the ERK/c-Jun signaling pathway. Chem Biol Interact 234: 274-281. doi: 10.1016/j.cbi.2014.11.013. go to article

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Phenotypic Information for AKR1B10(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: AKR1B10
	Familial Cancer Database: AKR1B10

* 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_LINOLEIC_ACID_METABOLISM KEGG_BUTANOATE_METABOLISM

Others
OMIM	604707; gene.
Orphanet
Disease	KEGG Disease: AKR1B10
	MedGen: AKR1B10 (Human Medical Genetics with Condition)
	ClinVar: AKR1B10
Phenotype	MGI: AKR1B10 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: AKR1B10

Mutations for AKR1B10

* 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
pancreas	AKR1B10	chr7	134216181	134216201	AKR1B10	chr7	134217976	134217996

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 AKR1B10 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=7

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=28)	Stat. for Synonymous SNVs (# total SNVs=17)

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
chr7:134221826-134221826	p.T192T	7
chr7:134217804-134217804	p.G134R	3
chr7:134221874-134221874	p.T208T	2
chr7:134212697-134212697	p.K12*	2
chr7:134215403-134215403	p.L25L	2
chr7:134223007-134223007	p.A268V	2
chr7:134217811-134217811	p.A136V	1
chr7:134223010-134223010	p.R269L	1
chr7:134215495-134215495	p.G56E	1
chr7:134221837-134221837	p.L196R	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=2

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			5	2		3		2			11	3				14	3		3
# mutation	1			4	2		3		2			12	3				15	3		4
nonsynonymous SNV	1			2	1		3		1			9	3				8	2		3
synonymous SNV				2	1				1			3					7	1		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
chr7:134221874	p.T208T	2
chr7:134221506	p.P81S	1
chr7:134215542	p.L157I	1
chr7:134222956	p.I254I	1
chr7:134217804	p.R90R	1
chr7:134221806	p.S163R	1
chr7:134215553	p.Q255P	1
chr7:134222961	p.E94Q	1
chr7:134217811	p.K177K	1
chr7:134212671	p.Q255H	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 AKR1B10 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 AKR1B10

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 AKR1B10

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	O60218; -.
Chemistry	ChEMBL	CHEMBL5983; -.
Organism-specific databases	PharmGKB	PA24676; -.
Organism-specific databases	CTD	57016; -.

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
DB02383	aldo-keto reductase family 1, member B10 (aldose reductase)	experimental	Tolrestat
DB03461	aldo-keto reductase family 1, member B10 (aldose reductase)	experimental	2'-Monophosphoadenosine 5'-Diphosphoribose
DB08772	aldo-keto reductase family 1, member B10 (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 AKR1B10

* 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