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 TPH1

Basic gene info.	Gene symbol	TPH1
	Gene name	tryptophan hydroxylase 1
	Synonyms	TPRH\|TRPH
	Cytomap	UCSC genome browser: 11p15.3-p14
	Genomic location	chr11 :18042083-18062335
	Type of gene	protein-coding
	RefGenes	NM_004179.2,
	Ensembl id	ENSG00000129167
	Description	L-tryptophan hydroxylaseindoleacetic acid-5-hydroxylasetryptophan 5-hydroxylase 1tryptophan 5-monooxygenase 1tryptophan hydroxylase (tryptophan 5-monooxygenase)
	Modification date	20141207
dbXrefs	MIM : 191060
	HGNC : HGNC
	HPRD : 01846
Protein	UniProt: P17752 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_TPH1
	BioGPS: 7166
	Gene Expression Atlas: ENSG00000129167
	The Human Protein Atlas: ENSG00000129167
Pathway	NCI Pathway Interaction Database: TPH1
	KEGG: TPH1
	REACTOME: TPH1
	ConsensusPathDB
	Pathway Commons: TPH1
Metabolism	MetaCyc: TPH1
	HUMANCyc: TPH1
Regulation	Ensembl's Regulation: ENSG00000129167
	miRBase: chr11 :18,042,083-18,062,335
	TargetScan: NM_004179
	cisRED: ENSG00000129167
Context	iHOP: TPH1
	cancer metabolism search in PubMed: TPH1
	UCL Cancer Institute: TPH1
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of TPH1 in cancer cell metabolism	1. Juhász C, Nahleh Z, Zitron I, Chugani DC, Janabi MZ, et al. (2012) Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies. Nuclear medicine and biology 39: 926-932. go to article

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Phenotypic Information for TPH1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: TPH1
	Familial Cancer Database: TPH1

* 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_TRYPTOPHAN_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM	191060; gene.
Orphanet
Disease	KEGG Disease: TPH1
	MedGen: TPH1 (Human Medical Genetics with Condition)
	ClinVar: TPH1
Phenotype	MGI: TPH1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: TPH1

Mutations for TPH1

* 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

There's no intra-chromosomal structural variation.

Sample

Symbol_a

Chr_a

Start_a

End_a

Symbol_b

Chr_b

Start_b

End_b

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 TPH1 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

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

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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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=35)	Stat. for Synonymous SNVs (# total SNVs=10)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=0)
There's no deleted snv.	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
chr11:18048097-18048097	p.R248Q	2
chr11:18051095-18051095	p.R145Q	2
chr11:18042711-18042711	p.E388*	2
chr11:18054916-18054916	p.E103*	2
chr11:18047154-18047154	p.A300T	2
chr11:18062260-18062260	p.R17T	1
chr11:18042699-18042699	p.T392A	1
chr11:18057575-18057575	p.H78D	1
chr11:18047155-18047155	p.G299G	1
chr11:18048117-18048117	p.F241L	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=3

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	2			5	2		2		4			10	2			1	7	3		7
# mutation	2			5	2		2		4			12	2			1	9	4		8
nonsynonymous SNV				4	2		2		3			9	2			1	8	3		6
synonymous SNV	2			1					1			3					1	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
chr11:18051095	p.R145Q	2
chr11:18054861	p.R142S	1
chr11:18057677	p.L20F	1
chr11:18044391	p.G294C	1
chr11:18048086	p.R121T	1
chr11:18054868	p.R17T	1
chr11:18062235	p.S290F	1
chr11:18045491	p.A119T	1
chr11:18048162	p.G16E	1
chr11:18054883	p.E283K	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 TPH1 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 TPH1

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


ABI3BP,CC2D2A,CDHR2,CHRM4,AMER3,IGSF1,INSC, MEP1A,MIXL1,MYOC,NEUROD4,RALYL,RNF133,RNF148, SEC14L5,SEZ6L,SLC18A1,SLC9C1,TKTL1,TNFAIP8L3,TPH1	C4BPA,CETN1,CYP7B1,GCC2,GK5,GPRIN3,HIVEP3, KNDC1,LCN15,LIPM,LRRC8B,NAA11,OR2A4,OSMR, RNF24,SLC25A37,SLC28A3,TPH1,UBTFL1,UTP20,YTHDC2

ADAM2,AGXT,C2CD4B,CCDC33,DLL1,FAM133A,FGL1, GIF,GP9,IL19,LCN8,MYO3B,PAGE1,PCCA, PPP4R4,RFX6,RTBDN,SSX4,TPH1,WFDC2,ZG16	AVPR1B,CFC1B,CRH,CYP2W1,GABRA6,INSL5,KLK3, KRTAP3-3,LMX1A,MYBPC1,NEUROD1,NKX2-2,PF4V1,RFX6, RIMS4,SLC38A11,SST,TBX4,TNNC1,TPH1,TTR

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 TPH1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P17752; -.
Chemistry	ChEMBL	CHEMBL5689; -.
Chemistry	GuidetoPHARMACOLOGY	1241; -.
Organism-specific databases	PharmGKB	PA355; -.
Organism-specific databases	CTD	7166; -.

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
DB00360	tryptophan hydroxylase 1	approved; investigational	Tetrahydrobiopterin
DB03271	tryptophan hydroxylase 1	experimental	7,8-Dihydro-L-Biopterin
DB00715	tryptophan hydroxylase 1	approved; investigational	Paroxetine
DB00176	tryptophan hydroxylase 1	approved; investigational	Fluvoxamine

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Cross referenced IDs for TPH1

* 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