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 XPO1

Basic gene info.	Gene symbol	XPO1
	Gene name	exportin 1
	Synonyms	CRM1\|emb\|exp1
	Cytomap	UCSC genome browser: 2p15
	Genomic location	chr2 :61705068-61765418
	Type of gene	protein-coding
	RefGenes	NM_003400.3,
	Ensembl id	ENSG00000082898
	Description	CRM1, yeast, homologchromosome region maintenance 1 homologchromosome region maintenance 1 protein homologexportin 1 (CRM1 homolog, yeast)exportin-1exportin-1 (required for chromosome region maintenance)
	Modification date	20141222
dbXrefs	MIM : 602559
	HGNC : HGNC
	Ensembl : ENSG00000082898
	HPRD : 03975
	Vega : OTTHUMG00000152316
Protein	UniProt: O14980 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_XPO1
	BioGPS: 7514
	Gene Expression Atlas: ENSG00000082898
	The Human Protein Atlas: ENSG00000082898
Pathway	NCI Pathway Interaction Database: XPO1
	KEGG: XPO1
	REACTOME: XPO1
	ConsensusPathDB
	Pathway Commons: XPO1
Metabolism	MetaCyc: XPO1
	HUMANCyc: XPO1
Regulation	Ensembl's Regulation: ENSG00000082898
	miRBase: chr2 :61,705,068-61,765,418
	TargetScan: NM_003400
	cisRED: ENSG00000082898
Context	iHOP: XPO1
	cancer metabolism search in PubMed: XPO1
	UCL Cancer Institute: XPO1
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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Phenotypic Information for XPO1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: XPO1
	Familial Cancer Database: XPO1

* 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 CLL ⁶,	Therapeutic Vulnerabilities in Cancer⁷

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/v505/n7484/full/nature12912.html,
7Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
REACTOME_METABOLISM_OF_MRNA REACTOME_METABOLISM_OF_RNA

Others
OMIM	602559; gene.
Orphanet
Disease	KEGG Disease: XPO1
	MedGen: XPO1 (Human Medical Genetics with Condition)
	ClinVar: XPO1
Phenotype	MGI: XPO1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: XPO1

Mutations for XPO1

* 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
haematopoietic_and_lymphoid_tissue	XPO1	chr2	61726887	61726887	XPO1	chr2	61726887	61726887

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 XPO1 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
AA559883	XPO1	1	64	2	61724028	61724091	XPO1	60	148	2	61722680	61724033
DB158037	ZNF100	1	86	19	21913286	21913371	XPO1	83	560	2	61749775	61764896
BG259252	XPO1	15	112	2	61715331	61715746	XPO1	110	729	2	61709608	61715358
BM462202	XPO1	16	109	2	61705205	61705298	XPO1	91	213	2	61705069	61705189
N53198	XPO1	23	360	2	61715625	61715962	TRAPPC9	354	381	8	141227840	141227867
DB198554	XPO1	1	294	2	61713792	61714085	XPO1	291	625	2	61715731	61716065

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=24

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=109)	Stat. for Synonymous SNVs (# total SNVs=20)

Stat. for Deletions (# total SNVs=2)	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
chr2:61719472-61719472	p.E571K	20
chr2:61715367-61715367	p.R749Q	6
chr2:61719471-61719471	p.E571V	4
chr2:61715726-61715726	p.N735Y	4
chr2:61722723-61722723	p.R305Q	3
chr2:61726051-61726051	p.?	3
chr2:61711203-61711203	p.F849Y	2
chr2:61715853-61715853	p.L692L	2
chr2:61712909-61712909	p.I834M	2
chr2:61729443-61729443	p.I102V	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=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	4	5	1	13			4		8	1		7	2	1			4	5		18
# mutation	4	4	1	13			4		8	1		8	2	1			4	9		22
nonsynonymous SNV	3	3	1	8			3		8	1		6	2				2	5		17
synonymous SNV	1	1		5			1					2		1			2	4		5

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
chr2:61719472	p.E571K	6
chr2:61715367	p.R749Q	4
chr2:61712950	p.S959S	2
chr2:61709610	p.Q821E	2
chr2:61722723	p.R305Q	2
chr2:61717834	p.V968V	1
chr2:61725817	p.P661P	1
chr2:61709537	p.Q437E	1
chr2:61719749	p.L255L	1
chr2:61753653	p.E655D	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 XPO1 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 XPO1

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


ASPM,BRCA2,CASC5,CEBPZ,CENPI,CKAP2L,ECT2, MSH2,MSH6,NAA25,NUP155,RIF1,SGOL1,SGOL2, SMC4,SMEK2,TMPO,TOPBP1,TTK,USP34,XPO1	FAM208A,C5orf51,FAM135A,FBXL4,GOPC,HERC4,IREB2, UFL1,MORC3,ICE2,PMS1,SCAI,SENP7,SCAF11, SMCHD1,SPAST,TIAL1,WDR36,XPO1,ZNF280D,ZNF770

ATAD5,BUB1,CCDC138,CEBPZ,DDX18,DNA2,FANCI, FBXO5,KIAA1524,MSH2,NCAPH,PMS1,PNPT1,POLR2D, PRPF40A,SGOL2,TMEM194A,TOPBP1,WDR43,WDR75,XPO1	CSE1L,DHX57,DNM1L,HAUS6,HNRNPA3,IARS,INTS2, IPO9,LBR,LUC7L2,MSH6,NEDD1,NUP107,NUP205, RBM26,RPGRIP1L,NEMF,TMEM194A,UBFD1,XPO1,XPO7

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 XPO1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	O14980; -.
Chemistry	ChEMBL	CHEMBL5661; -.
Organism-specific databases	PharmGKB	PA37418; -.
Organism-specific databases	CTD	7514; -.

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
DB00171	exportin 1 (CRM1 homolog, yeast)	approved; nutraceutical	Adenosine triphosphate
DB00864	exportin 1 (CRM1 homolog, yeast)	approved; investigational	Tacrolimus

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Cross referenced IDs for XPO1

* 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