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 RORA

Basic gene info.	Gene symbol	RORA
	Gene name	RAR-related orphan receptor A
	Synonyms	NR1F1\|ROR1\|ROR2\|ROR3\|RZR-ALPHA\|RZRA
	Cytomap	UCSC genome browser: 15q22.2
	Genomic location	chr15 :60780482-60884707
	Type of gene	protein-coding
	RefGenes	NM_002943.3, NM_134260.2,NM_134261.2,NM_134262.2,
	Ensembl id	ENSG00000069667
	Description	ROR-alphanuclear receptor ROR-alphanuclear receptor RZR-alphanuclear receptor subfamily 1 group F member 1retinoic acid receptor-related orphan receptor alpharetinoid-related orphan receptor alphathyroid hormone nuclear receptor alpha variant 4tran
	Modification date	20141222
dbXrefs	MIM : 600825
	HGNC : HGNC
	Ensembl : ENSG00000069667
	HPRD : 02896
	Vega : OTTHUMG00000132769
Protein	UniProt: P35398 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_RORA
	BioGPS: 6095
	Gene Expression Atlas: ENSG00000069667
	The Human Protein Atlas: ENSG00000069667
Pathway	NCI Pathway Interaction Database: RORA
	KEGG: RORA
	REACTOME: RORA
	ConsensusPathDB
	Pathway Commons: RORA
Metabolism	MetaCyc: RORA
	HUMANCyc: RORA
Regulation	Ensembl's Regulation: ENSG00000069667
	miRBase: chr15 :60,780,482-60,884,707
	TargetScan: NM_002943
	cisRED: ENSG00000069667
Context	iHOP: RORA
	cancer metabolism search in PubMed: RORA
	UCL Cancer Institute: RORA
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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

Cancer Description
Cancer	CGAP: RORA
	Familial Cancer Database: RORA

* 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
REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	600825; gene.
Orphanet
Disease	KEGG Disease: RORA
	MedGen: RORA (Human Medical Genetics with Condition)
	ClinVar: RORA
Phenotype	MGI: RORA (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: RORA

Mutations for RORA

* 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
haematopoietic_and_lymphoid_tissue	RORA	chr15	60808335	60808335		chr17	68060017	68060017
ovary	RORA	chr15	60835607	60835627		chr15	20101981	20102001
ovary	RORA	chr15	60846342	60846362		chr15	89610402	89610422
ovary	RORA	chr15	60852131	60852151	RORA	chr15	60853616	60853636
pancreas	RORA	chr15	60830773	60830793	RORA	chr15	60831670	60831690

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 RORA 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
BF858891	RORA	14	363	15	61371657	61372006	KLK3	353	447	19	51363680	51363778
BF091671	MRO	15	241	18	48321742	48321967	RORA	229	472	15	61473945	61474188
CV392982	RORA	10	310	15	61343402	61343701	BAI3	305	535	6	69352808	69353038

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=4

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=37)	Stat. for Synonymous SNVs (# total SNVs=9)

Stat. for Deletions (# total SNVs=2)	Stat. for Insertions (# total SNVs=1)

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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
chr15:60795033-60795033	p.R403H	3
chr15:60919479-60919479	p.R32I	2
chr15:60803679-60803679	p.S222L	2
chr15:60919495-60919495	p.R27*	2
chr15:60803461-60803461	p.G295S	2
chr15:60919521-60919521	p.P18L	2
chr15:60919533-60919533	p.E14G	2
chr15:60793176-60793176	p.F459L	1
chr15:60806876-60806876	p.S154S	1
chr15:60795746-60795746	p.L388I	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	1		6			1		2	1		8	3	2			4	5		12
# mutation	1	1		5			1		2	1		9	3	2			3	5		14
nonsynonymous SNV		1		4			1		1	1		6	3	2			2	4		11
synonymous SNV	1			1					1			3					1	1		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
chr15:60919533	p.R32T,RORA	2
chr15:60970872	p.P18L,RORA	2
chr15:60919479	p.E14G,RORA	2
chr15:60919521	p.T60T	2
chr15:60849084	p.V444V,RORA	1
chr15:60795032	p.T139T,RORA	1
chr15:60919532	p.F80L	1
chr15:60803725	p.G410V,RORA	1
chr15:60850430	p.G137W,RORA	1
chr15:60795042	p.I75V	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 RORA 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 RORA

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


ABCA6,AKAP13,CREBRF,DENND4A,DPP8,ELK3,FEM1B, FOXN3,KCTD12,LRCH1,MYO9A,PCNX,PIAS1,RAB8B, RORA,PEAK1,TBC1D2B,TCF4,VPS13C,ZEB1,ZEB2	AHCYL2,CEP85L,CUL5,DENND2C,DPP8,CCSER2,HECTD1, HERC1,IBTK,KIAA2018,LOC729082,MEF2A,NEDD4,OTUD4, PPTC7,PYGO1,RORA,SOS2,TNKS2,USP15,WDR47

A2M,AKAP2,AMOTL1,ARHGEF6,ATP8B2,DAAM2,FILIP1L, IL6ST,ITPR1,LBH,MAF,NR3C1,PLCL1,PTPLAD2, PTPRM,RORA,SLC9A9,SYT11,TCF4,WIPF1,ZIK1	ABCA3,EFS,ENO2,FGFR1,HSPA12A,KCNIP3,KCTD7, KLC1,LIX1L,NCAM1,NFIA,POU6F1,RIC3,RORA, SLC12A4,SLC45A1,SLC4A3,SYT11,TCF7L1,TMEM43,TRO

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 RORA

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P35398; -.
Chemistry	ChEMBL	CHEMBL5868; -.
Chemistry	GuidetoPHARMACOLOGY	598; -.
Organism-specific databases	PharmGKB	PA34630; -.
Organism-specific databases	CTD	6095; -.

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
DB00709	RAR-related orphan receptor A	approved; investigational	Lamivudine

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Cross referenced IDs for RORA

* 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