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 PDE4D

Basic gene info.	Gene symbol	PDE4D
	Gene name	phosphodiesterase 4D, cAMP-specific
	Synonyms	ACRDYS2\|DPDE3\|HSPDE4D\|PDE43\|PDE4DN2\|STRK1
	Cytomap	UCSC genome browser: 5q12
	Genomic location	chr5 :58264865-58295759
	Type of gene	protein-coding
	RefGenes	NM_001104631.1, NM_001165899.1,NM_001197218.1,NM_001197219.1,NM_001197220.1, NM_001197221.1,NM_001197222.1,NM_001197223.1,NM_006203.4,
	Ensembl id	ENSG00000113448
	Description	cAMP-specific 3',5'-cyclic phosphodiesterase 4DcAMP-specific phosphodiesterase PDE4D6phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)
	Modification date	20141207
dbXrefs	MIM : 600129
	HGNC : HGNC
	Ensembl : ENSG00000113448
	HPRD : 02530
	Vega : OTTHUMG00000162218
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PDE4D
	BioGPS: 5144
	Gene Expression Atlas: ENSG00000113448
	The Human Protein Atlas: ENSG00000113448
Pathway	NCI Pathway Interaction Database: PDE4D
	KEGG: PDE4D
	REACTOME: PDE4D
	ConsensusPathDB
	Pathway Commons: PDE4D
Metabolism	MetaCyc: PDE4D
	HUMANCyc: PDE4D
Regulation	Ensembl's Regulation: ENSG00000113448
	miRBase: chr5 :58,264,865-58,295,759
	TargetScan: NM_001104631
	cisRED: ENSG00000113448
Context	iHOP: PDE4D
	cancer metabolism search in PubMed: PDE4D
	UCL Cancer Institute: PDE4D
Assigned class in ccmGDB	C

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Phenotypic Information for PDE4D(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PDE4D
	Familial Cancer Database: PDE4D

* 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_PURINE_METABOLISM

Others
OMIM
Orphanet
Disease	KEGG Disease: PDE4D
	MedGen: PDE4D (Human Medical Genetics with Condition)
	ClinVar: PDE4D
Phenotype	MGI: PDE4D (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PDE4D

Mutations for PDE4D

* 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
prostate	PDE4D	chr5	59621985	59623985	NCOR2	chr12	124837154	124839154

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 PDE4D 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
DA282561	PDE4D	1	100	5	59129537	59129636	AGPAT4	101	575	6	161587303	161695030
DB236218	PDE4D	1	210	5	59064071	59064280	SLC16A9	208	580	10	61414072	61424081
BE928480	REPS1	68	299	6	139228509	139228740	PDE4D	299	325	5	59386751	59386781
AW993560	TAB2	8	160	6	149684678	149684831	PDE4D	146	342	5	58950802	58950999
BI019872	RAB37	14	226	17	72700776	72700988	PDE4D	219	373	5	58351301	58351453
DA522054	PDE4D	1	267	5	58883684	58883950	KCTD2	261	561	17	73059857	73060153
BF367933	PDE4D	1	139	5	59495558	59495702	PDE4D	133	414	5	59495678	59495960
DW442273	PDE4D	17	149	5	58676441	58676572	PDE4D	145	235	5	58677085	58677175
BF917173	PDE4D	1	445	5	58445976	58446420	KIAA1217	431	605	10	24835095	24835269

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=2

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=52)	Stat. for Synonymous SNVs (# total SNVs=7)

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
chr5:58511596-58511596	p.?	3
chr5:58270597-58270597	p.S639C	2
chr5:58285638-58285638	p.H330N	2
chr5:58271593-58271593	p.T499M	2
chr5:58270587-58270587	p.I642I	1
chr5:58273028-58273028	p.V430A	1
chr5:58285753-58285754	p.?	1
chr5:58511763-58511763	p.R27W	1
chr5:58270781-58270781	p.Q578*	1
chr5:58289264-58289264	p.T181N	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	6		10			6		2			7	5	1			10	3		10
# mutation	2	6		10			6		2			7	5	1			10	3		14
nonsynonymous SNV	2	6		9			5		1			5	2	1			8	1		10
synonymous SNV				1			1		1			2	3				2	2		4

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
chr5:58271593	p.R237Q,PDE4D	2
chr5:58481063	p.R44P	2
chr5:59284456	p.T411M,PDE4D	2
chr5:58270597	p.S75Y,PDE4D	1
chr5:58289244	p.A46A	1
chr5:58511744	p.C538C,PDE4D	1
chr5:58271584	p.E366K,PDE4D	1
chr5:59189364	p.L25L	1
chr5:58273131	p.E534K,PDE4D	1
chr5:58270599	p.V342V,PDE4D	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 PDE4D 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 PDE4D

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


AVPI1,C19orf57,LINC00473,CXCL5,ECEL1,EYA4,FLJ45079, FYN,LOC441177,LSAMP,MAPK4,MCTP2,PDE3A,PDE4D, PLD1,PON1,PPARGC1A,PTP4A1,SLC7A5,SMOC1,SPINK6	ACTC1,AGL,ART3,ASB2,ATP2A2,BVES,CTNNA3, DCAF6,DES,FLNC,FNDC5,KCNT1,LRRC2,MEF2C, NEXN,PDE4D,PHTF2,PLN,SGCA,SLC8A3,TMEM233

AKAP13,TMEM263,CRYBG3,ELL2,FAM114A1,IKZF2,IL6ST, KLF9,LHFPL2,MEF2A,PDE4B,PDE4D,PDE5A,PJA2, PLCL2,PPP1R12A,RAB27A,RAB8B,SGMS2,SNRK,TMTC2	ABI2,AMIGO2,ARHGAP23,DCBLD2,DENND5A,ENAH,FAM124A, FAM129A,FGF12,HSPA2,MAP9,MASP1,MPDZ,MTMR9, MYOCD,PDE4D,PKD2,PRKAA2,SRF,VGLL3,WWC2

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 PDE4D

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
DB00131	phosphodiesterase 4D, cAMP-specific	approved; nutraceutical	Adenosine monophosphate
DB00651	phosphodiesterase 4D, cAMP-specific	approved	Dyphylline
DB00920	phosphodiesterase 4D, cAMP-specific	approved	Ketotifen
DB01088	phosphodiesterase 4D, cAMP-specific	approved; investigational	Iloprost
DB01791	phosphodiesterase 4D, cAMP-specific	experimental	Piclamilast
DB01954	phosphodiesterase 4D, cAMP-specific	experimental	4-[3-(Cyclopentyloxy)-4-Methoxyphenyl]-2-Pyrrolidinone
DB01959	phosphodiesterase 4D, cAMP-specific	experimental	3,5-Dimethyl-1-(3-Nitrophenyl)-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB02676	phosphodiesterase 4D, cAMP-specific	experimental	2-[3-(2-Hydroxy-1,1-Dihydroxymethyl-Ethylamino)-Propylamino]-2-Hydroxymethyl-Propane-1,3-Diol
DB02918	phosphodiesterase 4D, cAMP-specific	experimental	6-(4-Difluoromethoxy-3-Methoxy-Phenyl)-2h-Pyridazin-3-One
DB03183	phosphodiesterase 4D, cAMP-specific	experimental	1-(4-Aminophenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB03606	phosphodiesterase 4D, cAMP-specific	experimental	(S)-Rolipram
DB03849	phosphodiesterase 4D, cAMP-specific	experimental	Cis-4-Cyano-4-[3-(Cyclopentyloxy)-4-Methoxyphenyl]Cyclohexanecarboxylic Acid
DB04149	phosphodiesterase 4D, cAMP-specific	experimental	(R)-Rolipram
DB04271	phosphodiesterase 4D, cAMP-specific	experimental	3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB04469	phosphodiesterase 4D, cAMP-specific	experimental	1-(4-Methoxyphenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB05266	phosphodiesterase 4D, cAMP-specific	approved; investigational	Ibudilast
DB06842	phosphodiesterase 4D, cAMP-specific	experimental	(4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one
DB07051	phosphodiesterase 4D, cAMP-specific	experimental	3,5-DIMETHYL-1-PHENYL-1H-PYRAZOLE-4-CARBOXYLIC ACID ETHYL ESTER
DB07954	phosphodiesterase 4D, cAMP-specific	experimental	3-ISOBUTYL-1-METHYLXANTHINE
DB08299	phosphodiesterase 4D, cAMP-specific	experimental	4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid
DB01151	phosphodiesterase 4D, cAMP-specific	approved	Desipramine
DB00472	phosphodiesterase 4D, cAMP-specific	approved	Fluoxetine
DB00465	phosphodiesterase 4D, cAMP-specific	approved	Ketorolac
DB00533	phosphodiesterase 4D, cAMP-specific	withdrawn; investigational	Rofecoxib

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Cross referenced IDs for PDE4D

* 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