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 RXRA

Basic gene info.	Gene symbol	RXRA
	Gene name	retinoid X receptor, alpha
	Synonyms	NR2B1
	Cytomap	UCSC genome browser: 9q34.3
	Genomic location	chr9 :137218315-137332431
	Type of gene	protein-coding
	RefGenes	NM_001291920.1, NM_001291921.1,NM_002957.5,
	Ensembl id	ENSG00000269571
	Description	nuclear receptor subfamily 2 group B member 1retinoic acid receptor RXR-alpharetinoid X nuclear receptor alpha
	Modification date	20141222
dbXrefs	MIM : 180245
	HGNC : HGNC
	HPRD : 01577
Protein	UniProt: P19793 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_RXRA
	BioGPS: 6256
	Gene Expression Atlas: ENSG00000269571
	The Human Protein Atlas: ENSG00000269571
Pathway	NCI Pathway Interaction Database: RXRA
	KEGG: RXRA
	REACTOME: RXRA
	ConsensusPathDB
	Pathway Commons: RXRA
Metabolism	MetaCyc: RXRA
	HUMANCyc: RXRA
Regulation	Ensembl's Regulation: ENSG00000269571
	miRBase: chr9 :137,218,315-137,332,431
	TargetScan: NM_001291920
	cisRED: ENSG00000269571
Context	iHOP: RXRA
	cancer metabolism search in PubMed: RXRA
	UCL Cancer Institute: RXRA
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of RXRA in cancer cell metabolism	1. Deepa PR, Vandhana S, Krishnakumar S (2013) Fatty acid synthase inhibition induces differential expression of genes involved in apoptosis and cell proliferation in ocular cancer cells. Nutrition and cancer 65: 311-316. go to article

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

Cancer Description
Cancer	CGAP: RXRA
	Familial Cancer Database: RXRA

* 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,	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/vaop/ncurrent/full/nature12965.html,
7Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	180245; gene.
Orphanet
Disease	KEGG Disease: RXRA
	MedGen: RXRA (Human Medical Genetics with Condition)
	ClinVar: RXRA
Phenotype	MGI: RXRA (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: RXRA

Mutations for RXRA

* 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	RXRA	chr9	137221922	137222322	LUC7L3	chr17	48819027	48819427
ovary	RXRA	chr9	137303708	137303728	RXRA	chr9	137305107	137305127

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 RXRA 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
AW881282	RXRA	30	291	9	137328444	137328705	RXRA	288	368	9	137325987	137328326
AW881216	RXRA	8	276	9	137328437	137328705	RXRA	273	360	9	137325987	137328333
BM978893	RXRA	19	107	9	137332343	137332431	LRBA	106	610	4	151283588	151284092

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=16

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=26)	Stat. for Synonymous SNVs (# total SNVs=16)

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
chr9:137328351-137328351	p.S427F	16
chr9:137309139-137309139	p.Y249F	2
chr9:137320990-137320990	p.R316L	2
chr9:137309140-137309140	p.Y249Y	2
chr9:137328442-137328442	p.A457A	2
chr9:137328331-137328331	p.L420L	2
chr9:137300040-137300040	p.P109S	2
chr9:137309028-137309028	p.G212D	2
chr9:137328348-137328348	p.R426H	2
chr9:137300840-137300840	p.T162M	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=5

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	13	1		8	2		4		1			1	5	1			3	6	1	4
# mutation	7	1		8	2		4		1			1	5	1			3	7	1	4
nonsynonymous SNV	6	1		6	2		4					1	2	1			3	5		2
synonymous SNV	1			2					1				3					2	1	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
chr9:137328351	p.S330F,RXRA	7
chr9:137320990	p.R219H,RXRA	2
chr9:137300887	p.P12S,RXRA	1
chr9:137321027	p.S220F,RXRA	1
chr9:137293688	p.P349S,RXRA	1
chr9:137300950	p.A39T,RXRA	1
chr9:137321028	p.L229L,RXRA	1
chr9:137328357	p.D351G,RXRA	1
chr9:137300015	p.V52A,RXRA	1
chr9:137309085	p.T231T,RXRA	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 RXRA 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 RXRA

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


ABCA2,ALAD,ANAPC2,PRRC2B,CACFD1,EHMT1,FAM73B, JMJD7-PLA2G4B,PPP1R26,MED22,MXD4,NDOR1,PKD1,PPP2R4, RGS12,RXRA,TAOK2,TBC1D13,TNRC18,USP20,ZER1	ABCD1,ACADS,AGPAT2,ALDH2,ANXA6,ADIRF,C14orf180, CAMK1,CEBPA,COL4A2,CSPG4,GYPC,ITGA7,LOC80054, PLA2G16,PNPLA2,POLR2E,PPP1R1A,RXRA,ST6GALNAC6,TMEM132C

PRRC2B,MIR600HG,CASZ1,CIZ1,NELFB,CORO2A,DAB2IP, DENND1A,EHMT1,EXD3,FAM73B,GPR107,ARHGAP35,KIAA0368, PPP1R26,RAPGEF1,RXRA,TBC1D13,TSC1,WDR37,ZER1	AGPAT3,ARHGEF11,ATG9A,BAHD1,BTBD9,CLIP2,DGCR2, ERBB2,ERBB3,ARHGAP35,KIAA1522,MAST2,N4BP1,PTPRF, RAB40C,RNPEPL1,RXRA,SIPA1L3,SPINT1,SPPL3,TNIP1

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 RXRA

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P19793; -.
Chemistry	ChEMBL	CHEMBL2363071; -.
Chemistry	GuidetoPHARMACOLOGY	610; -.
Organism-specific databases	PharmGKB	PA34890; -.
Organism-specific databases	CTD	6256; -.

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
DB00210	retinoid X receptor, alpha	approved	Adapalene
DB00307	retinoid X receptor, alpha	approved; investigational	Bexarotene
DB00459	retinoid X receptor, alpha	approved	Acitretin
DB00523	retinoid X receptor, alpha	approved; investigational	Alitretinoin
DB00749	retinoid X receptor, alpha	approved; investigational	Etodolac
DB00926	retinoid X receptor, alpha	withdrawn	Etretinate
DB07557	retinoid X receptor, alpha	experimental	(5BETA)-PREGNANE-3,20-DIONE
DB07863	retinoid X receptor, alpha	experimental	2-chloro-5-nitro-N-phenylbenzamide
DB08063	retinoid X receptor, alpha	experimental	1-BENZYL-3-(4-METHOXYPHENYLAMINO)-4-PHENYLPYRROLE-2,5-DIONE
DB08402	retinoid X receptor, alpha	experimental	2-[(2,4-DICHLOROBENZOYL)AMINO]-5-(PYRIMIDIN-2-YLOXY)BENZOIC ACID
DB08601	retinoid X receptor, alpha	experimental	tributylstannanyl
DB00755	retinoid X receptor, alpha	approved; nutraceutical; investigational	Tretinoin
DB00741	retinoid X receptor, alpha	approved	Hydrocortisone
DB01132	retinoid X receptor, alpha	approved; investigational	Pioglitazone
DB00412	retinoid X receptor, alpha	approved; investigational	Rosiglitazone
DB00197	retinoid X receptor, alpha	withdrawn	Troglitazone

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Cross referenced IDs for RXRA

* 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