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 TYR

Basic gene info.	Gene symbol	TYR
	Gene name	tyrosinase
	Synonyms	ATN\|CMM8\|OCA1\|OCA1A\|OCAIA\|SHEP3
	Cytomap	UCSC genome browser: 11q14.3
	Genomic location	chr11 :88911039-89028927
	Type of gene	protein-coding
	RefGenes	NM_000372.4,
	Ensembl id	ENSG00000077498
	Description	LB24-ABSK29-ABmonophenol monooxygenaseoculocutaneous albinism IAtumor rejection antigen AB
	Modification date	20141219
dbXrefs	MIM : 606933
	HGNC : HGNC
	Ensembl : ENSG00000077498
	HPRD : 06086
	Vega : OTTHUMG00000167294
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_TYR
	BioGPS: 7299
	Gene Expression Atlas: ENSG00000077498
	The Human Protein Atlas: ENSG00000077498
Pathway	NCI Pathway Interaction Database: TYR
	KEGG: TYR
	REACTOME: TYR
	ConsensusPathDB
	Pathway Commons: TYR
Metabolism	MetaCyc: TYR
	HUMANCyc: TYR
Regulation	Ensembl's Regulation: ENSG00000077498
	miRBase: chr11 :88,911,039-89,028,927
	TargetScan: NM_000372
	cisRED: ENSG00000077498
Context	iHOP: TYR
	cancer metabolism search in PubMed: TYR
	UCL Cancer Institute: TYR
Assigned class in ccmGDB	C

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

Cancer Description
Cancer	CGAP: TYR
	Familial Cancer Database: TYR

* 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_TYROSINE_METABOLISM KEGG_RIBOFLAVIN_METABOLISM

Others
OMIM
Orphanet
Disease	KEGG Disease: TYR
	MedGen: TYR (Human Medical Genetics with Condition)
	ClinVar: TYR
Phenotype	MGI: TYR (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: TYR

Mutations for TYR

* 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

There's no structural variation information in COSMIC data for this gene.

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows TYR 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=8

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=116)	Stat. for Synonymous SNVs (# total SNVs=25)

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
chr11:88911358-88911358	p.S79S	6
chr11:88924500-88924500	p.D317G	4
chr11:88911234-88911234	p.P38L	3
chr11:88911329-88911329	p.P70S	3
chr11:88961106-88961106	p.P384P	2
chr11:88911170-88911170	p.A17T	2
chr11:88911926-88911926	p.F269V	2
chr11:88911881-88911881	p.G254S	2
chr11:88961126-88961126	p.A391E	2
chr11:88961022-88961022	p.D356E	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=4

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	3	8	1	16	1		4		1			20	9	3			4	12	1	10
# mutation	3	8	1	13	1		4		1			22	9	3			4	12	1	14
nonsynonymous SNV	3	6		8	1		2		1			20	9	1			4	9		11
synonymous SNV		2	1	5			2					2		2				3	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
chr11:88924500	p.D317G	4
chr11:88911358	p.N261K	2
chr11:88911234	p.P38L	2
chr11:88911881	p.S79S	2
chr11:88911904	p.G254R	2
chr11:89018021	p.Y156C	1
chr11:88911329	p.N261T	1
chr11:88911788	p.A357D	1
chr11:88911926	p.L452I	1
chr11:89028412	p.S27S	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 TYR 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 TYR

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


LURAP1L,CT45A1,CT45A3,DHRS2,FRG2B,GABPB1,HGC6.3, LOC643008,MAGEA8,MAGEB18,NAP1L6,RGS5,RPL3L,SPPL2A, SUMO2,TYRP1,UGT2B10,UGT2B15,USP29,USP8,ZIM3	ACTC1,ALDH1B1,C20orf166-AS1,CAMK2G,CASQ2,FYCO1,INPP5A, ITIH4,LGI1,LOC401093,LRRC7,MN1,MUSTN1,PDE4C, PDE4D,PLN,SGCD,SRRM4,SYNPO2,TYRP1,UNC13C

ADCY2,NREP,CST5,DAAM2,ELN,FOXF1,GJD2, GPBAR1,LRRC10,LSAMP,LTBP1,MFAP2,NKX2-3,OSBPL6, PCDH18,RCAN2,RGMA,RIMS1,SLC24A3,TCF21,TYRP1	ABCC12,AMBN,ANO4,CALML5,CAPNS2,CCDC63,CLDN19, LOC100133920,MUCL1,NKX6-1,OR4A16,OR6B2,OR7E24,OR8D2, PGK2,SCGB2A2,SNORA13,SNORA58,TCF23,TYRP1,WFDC8

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 TYR

Cross-referenced pharmacological DB IDs from Uniprot

DB Category

DB Name

DB's ID and Url link

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
DB00157	tyrosinase	approved; nutraceutical	NADH
DB00548	tyrosinase	approved	Azelaic Acid
DB00600	tyrosinase	approved	Monobenzone
DB01055	tyrosinase	approved	Mimosine

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Cross referenced IDs for TYR

* 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