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 PDE10A

Basic gene info.	Gene symbol	PDE10A
	Gene name	phosphodiesterase 10A
	Synonyms	HSPDE10A
	Cytomap	UCSC genome browser: 6q26
	Genomic location	chr6 :165740775-166075588
	Type of gene	protein-coding
	RefGenes	NM_001130690.2, NR_045597.1,NM_006661.2,
	Ensembl id	ENSG00000112541
	Description	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10AdJ416F21.1 (phosphodiesterase 10A)phosphodiesterase 10A1 (PDE10A1)
	Modification date	20141218
dbXrefs	MIM : 610652
	HGNC : HGNC
	Ensembl : ENSG00000112541
	HPRD : 17828
	Vega : OTTHUMG00000015986
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PDE10A
	BioGPS: 10846
	Gene Expression Atlas: ENSG00000112541
	The Human Protein Atlas: ENSG00000112541
Pathway	NCI Pathway Interaction Database: PDE10A
	KEGG: PDE10A
	REACTOME: PDE10A
	ConsensusPathDB
	Pathway Commons: PDE10A
Metabolism	MetaCyc: PDE10A
	HUMANCyc: PDE10A
Regulation	Ensembl's Regulation: ENSG00000112541
	miRBase: chr6 :165,740,775-166,075,588
	TargetScan: NM_001130690
	cisRED: ENSG00000112541
Context	iHOP: PDE10A
	cancer metabolism search in PubMed: PDE10A
	UCL Cancer Institute: PDE10A
Assigned class in ccmGDB	C

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Phenotypic Information for PDE10A(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PDE10A
	Familial Cancer Database: PDE10A

* 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: PDE10A
	MedGen: PDE10A (Human Medical Genetics with Condition)
	ClinVar: PDE10A
Phenotype	MGI: PDE10A (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PDE10A

Mutations for PDE10A

* 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
ovary	PDE10A	chr6	165957101	165957121	CAB39	chr2	231651940	231651960
ovary	PDE10A	chr6	165957101	165957121	CAB39	chr2	231651941	231651961
pancreas	PDE10A	chr6	165799859	165799879	PDE10A	chr6	165800017	165800037
pancreas	PDE10A	chr6	166033121	166033141	PDE10A	chr6	166032925	166032945
pancreas	PDE10A	chr6	166037479	166037499	JPX	chr23	73187115	73187135

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 PDE10A 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	ns	ovary	pancre	prost	skin	stoma	thyro	urina
Total # sample	2	5		1			4		2		2			2			2
GAIN (# sample)	1										1			1
LOSS (# sample)	1	5		1			4		2		1			1			2

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=127)	Stat. for Synonymous SNVs (# total SNVs=38)

Stat. for Deletions (# total SNVs=1)	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
chr6:165808689-165808689	p.R486W	2
chr6:165756927-165756927	p.V674I	2
chr6:165832235-165832235	p.R286C	2
chr6:165809889-165809889	p.S436S	2
chr6:165863794-165863794	p.Q84Q	2
chr6:165756970-165756970	p.M659I	2
chr6:165827045-165827045	p.E398*	2
chr6:165863797-165863797	p.E83D	2
chr6:165746585-165746585	p.R757*	2
chr6:165862431-165862431	p.L117L	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=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	1	6		16	4		14		1			30	12	4	1	1	15	7		10
# mutation	1	7		16	6		14		1			31	13	4	1	1	16	7		14
nonsynonymous SNV	1	5		14	5		12		1			27	8	3	1	1	11	5		11
synonymous SNV		2		2	1		2					4	5	1			5	2		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
chr6:165863797	p.I112I	2
chr6:165746557	p.S776L	2
chr6:165862423	p.F503V	2
chr6:165808737	p.F578F	2
chr6:165801865	p.R296C	2
chr6:165827121	p.R496W	2
chr6:165863740	p.I382I	2
chr6:165806284	p.E93D	2
chr6:165809905	p.G480C	2
chr6:165832235	p.T441M	2

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 PDE10A 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 PDE10A

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


ALOX12,ARNTL2,ATF7IP,C12orf4,C12orf5,CHRNB1,CSGALNACT1, DCBLD1,DDX52,ECEL1,FXYD7,GOLGA8F,HNF1B,PDE10A, PPFIBP1,ROS1,TMEM45A,ZNF254,ZNF536,ZNF675,ZNF681	ASAP1,ASAP2,ATP13A3,CLTC,CYSLTR1,DPY19L1,FGF7, FUT11,HRH1,PAK2,PDE10A,PHACTR2,RAB23,RECQL, RGL1,SAMHD1,SLFN11,SRGAP2,TBC1D12,TCP11L1,TRAM2

VSTM5,LINC00261,CEP85L,CACNA1H,CCL26,CD109,DAPK1, DLK2,DUSP4,DZIP1L,FAM114A1,FAM167A,FAM46A,GRIP2, HCN2,MIA3,PDE10A,RNF144B,RNF152,SMCHD1,STIM2	DOK5,FGF10,HSD17B6,KLHL41,KIAA0408,KLHL38,LONRF2, MASP1,MOV10L1,MYOCD,NMNAT2,PALMD,PCDHGA5,PDE10A, RASGRF2,RBMS1,SAMD4A,STXBP5L,SYDE2,SLC35G2,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 PDE10A

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
DB00975	phosphodiesterase 10A	approved	Dipyridamole
DB01113	phosphodiesterase 10A	approved	Papaverine
DB08383	phosphodiesterase 10A	experimental	4,5-bis(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazole
DB08384	phosphodiesterase 10A	experimental	2-({4-[4-(pyridin-4-ylmethyl)-1H-pyrazol-3-yl]phenoxy}methyl)quinoline
DB08386	phosphodiesterase 10A	experimental	2-{[4-(4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinoline
DB08387	phosphodiesterase 10A	experimental	2-{[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinoline
DB08389	phosphodiesterase 10A	experimental	6,7-DIMETHOXY-4-[(3R)-3-(2-NAPHTHYLOXY)PYRROLIDIN-1-YL]QUINAZOLINE
DB08391	phosphodiesterase 10A	experimental	6,7-DIMETHOXY-4-[(3R)-3-(QUINOXALIN-2-YLOXY)PYRROLIDIN-1-YL]QUINAZOLINE
DB08811	phosphodiesterase 10A	approved	Tofisopam
DB01151	phosphodiesterase 10A	approved	Desipramine
DB00472	phosphodiesterase 10A	approved	Fluoxetine

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Cross referenced IDs for PDE10A

* 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