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 PAH

Basic gene info.	Gene symbol	PAH
	Gene name	phenylalanine hydroxylase
	Synonyms	PH\|PKU\|PKU1
	Cytomap	UCSC genome browser: 12q22-q24.2
	Genomic location	chr12 :103232103-103311381
	Type of gene	protein-coding
	RefGenes	NM_000277.1,
	Ensembl id	ENSG00000171759
	Description	phe-4-monooxygenasephenylalanine 4-monooxygenasephenylalanine-4-hydroxylase
	Modification date	20141219
dbXrefs	MIM : 612349
	HGNC : HGNC
	Ensembl : ENSG00000171759
	HPRD : 08943
	Vega : OTTHUMG00000169966
Protein	UniProt: P00439 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PAH
	BioGPS: 5053
	Gene Expression Atlas: ENSG00000171759
	The Human Protein Atlas: ENSG00000171759
Pathway	NCI Pathway Interaction Database: PAH
	KEGG: PAH
	REACTOME: PAH
	ConsensusPathDB
	Pathway Commons: PAH
Metabolism	MetaCyc: PAH
	HUMANCyc: PAH
Regulation	Ensembl's Regulation: ENSG00000171759
	miRBase: chr12 :103,232,103-103,311,381
	TargetScan: NM_000277
	cisRED: ENSG00000171759
Context	iHOP: PAH
	cancer metabolism search in PubMed: PAH
	UCL Cancer Institute: PAH
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of PAH in cancer cell metabolism	1. Mantey JA, Rekhadevi PV, Diggs DL, Ramesh A (2014) Metabolism of benzo (a) pyrene by subcellular fractions of gastrointestinal (GI) tract and liver in Apc Min mouse model of colon cancer. Tumor Biology 35: 4929-4935. go to article

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

Cancer Description
Cancer	CGAP: PAH
	Familial Cancer Database: PAH

* 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_PHENYLALANINE_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM	261600; phenotype. 612349; gene.
Orphanet	2209; Maternal hyperphenylalaninemia. 293284; Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria. 79253; Mild phenylketonuria. 79254; Classical phenylketonuria. 79651; Mild hyperphenylalaninemia.
Disease	KEGG Disease: PAH
	MedGen: PAH (Human Medical Genetics with Condition)
	ClinVar: PAH
Phenotype	MGI: PAH (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PAH

Mutations for PAH

* 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
pancreas	PAH	chr12	103278332	103278352	PAH	chr12	103278467	103278487

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 PAH 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=5

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=63)	Stat. for Synonymous SNVs (# total SNVs=19)

Stat. for Deletions (# total SNVs=3)	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
chr12:103288633-103288633	p.E78K	3
chr12:103240729-103240729	p.E305K	3
chr12:103237469-103237469	p.L385H	3
chr12:103288533-103288533	p.R111Q	3
chr12:103249000-103249000	p.N207S	2
chr12:103246597-103246597	p.E280K	2
chr12:103234265-103234265	p.F410I	2
chr12:103240696-103240696	p.E316K	2
chr12:103246614-103246614	p.K274T	2
chr12:103246708-103246708	p.R243*	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	3	2		20	2		6		4	1		6	4	4			15	7		2
# mutation	3	2		21	2		6		4	1		7	4	4			15	7		2
nonsynonymous SNV	2	2		15	2		4		3	1		5	3	1			9	5		2
synonymous SNV	1			6			2		1			2	1	3			6	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
chr12:103249074	p.R111Q	3
chr12:103288533	p.E182E	3
chr12:103245469	p.G10S	2
chr12:103249075	p.S303F	2
chr12:103310881	p.K274T	2
chr12:103246614	p.E182G	2
chr12:103288665	p.I174I	1
chr12:103232972	p.L62Q	1
chr12:103246688	p.C445F	1
chr12:103237477	p.V329L	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 PAH 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 PAH

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


AATK,ADARB2,ARSG,ASB16,BAIAP3,CCDC151,GDF15, GOLGA2P3Y,PAH,PSG10P,PSG4,PSG5,PSG6,PSG9, RTP2,SEMA3B,SLC16A6,TLX2,UNC5CL,VWA5B2,WNT3	AK5,C1orf74,C3orf14,CD9,DKFZP586I1420,ERP27,FAAH2, HHAT,IRF6,KIF5C,LIPH,MYO6,PAH,PAK6, PLEKHA6,POF1B,SDC4,SHISA2,VAV3,VEPH1,WISP3

ADAMTS20,ALDH4A1,AMACR,CDH26,CT47A1,ENGASE,EYA1, MROH5,GCG,GRPR,ITGA2B,LOC340357,LOC541473,METAP1D, PAH,PMFBP1,QPRT,SLC5A6,VIL1,XAGE2,ZNRF3	AMBP,APOA2,C3P1,C8B,CEL,CPB2,CYP2E1, DNAJB8,F2,FGB,FGG,HAO1,KIR3DP1,KRTAP4-11, KRTAP5-3,LECT2,LOC100129935,LINC00160,OR1N1,PAGE4,PAH,

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 PAH

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P00439; -.
Chemistry	ChEMBL	CHEMBL3076; -.
Chemistry	GuidetoPHARMACOLOGY	1240; -.
Organism-specific databases	PharmGKB	PA32911; -.
Organism-specific databases	CTD	5053; -.

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
DB00120	phenylalanine hydroxylase	approved; nutraceutical	L-Phenylalanine
DB00360	phenylalanine hydroxylase	approved; investigational	Tetrahydrobiopterin
DB00368	phenylalanine hydroxylase	approved	Norepinephrine
DB00668	phenylalanine hydroxylase	approved	Epinephrine
DB02562	phenylalanine hydroxylase	experimental	Quinonoid 7,8-Tetrahydrobiopterin
DB02692	phenylalanine hydroxylase	experimental	(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin
DB03673	phenylalanine hydroxylase	experimental	Beta(2-Thienyl)Alanine
DB04400	phenylalanine hydroxylase	experimental	7,8-Dihydrobiopterin
DB04419	phenylalanine hydroxylase	experimental	Norleucine
DB06262	phenylalanine hydroxylase	approved; investigational	Droxidopa
DB03271	phenylalanine hydroxylase	experimental	7,8-Dihydro-L-Biopterin
DB00143	phenylalanine hydroxylase	approved; nutraceutical	Glutathione
DB00135	phenylalanine hydroxylase	approved; nutraceutical	L-Tyrosine

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Cross referenced IDs for PAH

* 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