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 FBXW7

Basic gene info.	Gene symbol	FBXW7
	Gene name	F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
	Synonyms	AGO\|CDC4\|FBW6\|FBW7\|FBX30\|FBXO30\|FBXW6\|SEL-10\|SEL10\|hAgo\|hCdc4
	Cytomap	UCSC genome browser: 4q31.3
	Genomic location	chr4 :153332311-153456393
	Type of gene	protein-coding
	RefGenes	NM_001013415.1, NM_001257069.1,NM_018315.4,NM_033632.3,
	Ensembl id	ENSG00000109670
	Description	F-box and WD-40 domain protein 7 (archipelago homolog, Drosophila)F-box protein FBW7F-box protein FBX30F-box protein SEL-10F-box/WD repeat-containing protein 7archipelagohomolog of C elegans sel-10
	Modification date	20141222
dbXrefs	MIM : 606278
	HGNC : HGNC
	Ensembl : ENSG00000109670
	HPRD : 05888
	Vega : OTTHUMG00000185246
Protein	UniProt: Q969H0 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_FBXW7
	BioGPS: 55294
	Gene Expression Atlas: ENSG00000109670
	The Human Protein Atlas: ENSG00000109670
Pathway	NCI Pathway Interaction Database: FBXW7
	KEGG: FBXW7
	REACTOME: FBXW7
	ConsensusPathDB
	Pathway Commons: FBXW7
Metabolism	MetaCyc: FBXW7
	HUMANCyc: FBXW7
Regulation	Ensembl's Regulation: ENSG00000109670
	miRBase: chr4 :153,332,311-153,456,393
	TargetScan: NM_001013415
	cisRED: ENSG00000109670
Context	iHOP: FBXW7
	cancer metabolism search in PubMed: FBXW7
	UCL Cancer Institute: FBXW7
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of FBXW7 in cancer cell metabolism	1. Okazaki H, Matsunaga N, Fujioka T, Okazaki F, Akagawa Y, et al. (2014) Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma. Cancer Res 74: 543-551. doi: 10.1158/0008-5472.CAN-12-3241. go to article 2. Xu Y, Swartz KL, Siu KT, Bhattacharyya M, Minella AC (2014) Fbw7-dependent cyclin E regulation ensures terminal maturation of bone marrow erythroid cells by restraining oxidative metabolism. Oncogene 33: 3161-3171. doi: 10.1038/onc.2013.289. pmid: 3939062. go to article 3. Li S, Oh YT, Yue P, Khuri FR, Sun SY (2015) Inhibition of mTOR complex 2 induces GSK3/FBXW7-dependent degradation of sterol regulatory element-binding protein 1 (SREBP1) and suppresses lipogenesis in cancer cells. Oncogene. doi: 10.1038/onc.2015.123. go to article

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Phenotypic Information for FBXW7(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: FBXW7
	Familial Cancer Database: FBXW7

* 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 BLCA ⁶, COAD ⁷, CRC ⁸, LUSC ⁹, UCEC ¹⁰, STAD ¹¹,	Therapeutic Vulnerabilities in Cancer¹²

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,
6 http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12965.html,
7 http://www.nature.com/nature/journal/v487/n7407/full/nature11252.html,
8 http://www.nature.com/nature/journal/v505/n7484/full/nature12912.html,
9 http://www.nature.com/nature/journal/v489/n7417/full/nature11404.html,
10 http://www.nature.com/nature/journal/v497/n7447/full/nature12113.html,
11 http://www.nature.com/nature/journal/v513/n7517/full/nature13480.html,
12Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
REACTOME_METABOLISM_OF_PROTEINS

Others
OMIM	606278; gene.
Orphanet
Disease	KEGG Disease: FBXW7
	MedGen: FBXW7 (Human Medical Genetics with Condition)
	ClinVar: FBXW7
Phenotype	MGI: FBXW7 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: FBXW7

Mutations for FBXW7

* 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

* Inter-chromosomal variantions includes 'interchromosomal amplicon to amplicon', 'interchromosomal amplicon to non-amplified dna', 'interchromosomal insertion', 'Interchromosomal unknown type'.

- 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
breast	FBXW7	chr4	153417751	153417751		chr4	153462101	153462101
ovary	FBXW7	chr4	153390842	153390862		chr19	523678	523698
ovary	FBXW7	chr4	153390842	153390862		chr19	523680	523700
ovary	FBXW7	chr4	153440103	153440123	FBXW7	chr4	153375517	153375537

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 FBXW7 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
DQ177302	RUNX1	1	275	21	36219767	36220044	FBXW7	259	279	4	153332704	153332724
AI133397	FBXW7	8	607	4	153250162	153250761	KLF12	599	820	13	74683445	74683666
BF089643	FBXW7	22	206	4	153244074	153244258	PRR4	197	406	12	10998476	10999779

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=218

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=722)	Stat. for Synonymous SNVs (# total SNVs=60)

Stat. for Deletions (# total SNVs=17)	Stat. for Insertions (# total SNVs=16)

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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
chr4:153249385-153249385	p.R465C	94
chr4:153249384-153249384	p.R465H	81
chr4:153247289-153247289	p.R505S	80
chr4:153247366-153247366	p.R479L	53
chr4:153247288-153247288	p.R505L	27
chr4:153244092-153244092	p.R689W	18
chr4:153245446-153245446	p.S582L	17
chr4:153251907-153251907	p.R367*	15
chr4:153258983-153258983	p.R278*	13
chr4:153244185-153244185	p.R658*	10

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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=21

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	5	1	130	1		13	1	3	1		9	10	6	1		9	19	1	36
# mutation	6	5	1	97	1		11	1	3	1		9	8	6	1		10	12	1	24
nonsynonymous SNV	6	5	1	69	1		10	1	2	1		6	5	5	1		9	11	1	23
synonymous SNV				30			1		1			3	3	1			1	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
chr4:153249385	p.R347C,FBXW7	22
chr4:153247289	p.R387G,FBXW7	20
chr4:153249384	p.R347H,FBXW7	18
chr4:153247366	p.R361P,FBXW7	8
chr4:153244092	p.R571W,FBXW7	6
chr4:153249457	p.R323W,FBXW7	5
chr4:153332917	p.R387H,FBXW7	4
chr4:153247288	p.G305V,FBXW7	4
chr4:153244078	p.R347R,FBXW7	4
chr4:153249510	p.R13R,FBXW7	4

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 FBXW7 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 FBXW7

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


C10orf90,CARD6,CYYR1,DDX26B,FBXW7,FTMT,GPM6B, HPS5,KIAA0922,KIT,OTUD4,PLCG2,PLRG1,RAPGEF2, RGS2,S100B,SFRP1,SOX10,TANK,TIGD2,TRIM2	C15orf41,CLPX,CPEB3,CUL5,AMER1,FBXW7,GFM2, MED14,NAA25,OTUD4,PARG,RBL1,RFESD,RFX7, SACS,SOS2,THAP9,TLK2,UBE3A,ZBTB43,ZNF41

BTAF1,CCDC39,FBXW7,FLJ40330,GVINP1,ITK,JAK3, KCNA3,KIAA0125,NKTR,NLRC3,P2RY8,PARP15,PPP1R16B, PVRIG,SLFN14,TMEM156,TTN,WSB1,ZAP70,ZNF831	ANKLE2,CDV3,E2F3,FBXW7,FCRL5,EHMT1-IT1,FOXO1, GAPVD1,GLCCI1,LRIG2,MAPK1IP1L,MON2,NCRNA00120,NUP153, PLAC4,PSME4,PTPN1,RALGAPA1,RCOR1,SETX,SMEK1

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 FBXW7

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA28054; -.
Organism-specific databases	CTD	55294; -.

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
DB00877	F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase	approved; investigational	Sirolimus

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Cross referenced IDs for FBXW7

* 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