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 ADCY4

Basic gene info.	Gene symbol	ADCY4
	Gene name	adenylate cyclase 4
	Synonyms	AC4
	Cytomap	UCSC genome browser: 14q12
	Genomic location	chr14 :24787554-24804277
	Type of gene	protein-coding
	RefGenes	NM_001198568.1, NM_001198592.1,NM_139247.3,
	Ensembl id	ENSG00000129467
	Description	ATP pyrophosphate-lyase 4adenylate cyclase type 4adenylate cyclase type IVadenylyl cyclase 4
	Modification date	20141207
dbXrefs	MIM : 600292
	HGNC : HGNC
	Ensembl : ENSG00000129467
	HPRD : 11614
	Vega : OTTHUMG00000029347
Protein	UniProt: Q8NFM4 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ADCY4
	BioGPS: 196883
	Gene Expression Atlas: ENSG00000129467
	The Human Protein Atlas: ENSG00000129467
Pathway	NCI Pathway Interaction Database: ADCY4
	KEGG: ADCY4
	REACTOME: ADCY4
	ConsensusPathDB
	Pathway Commons: ADCY4
Metabolism	MetaCyc: ADCY4
	HUMANCyc: ADCY4
Regulation	Ensembl's Regulation: ENSG00000129467
	miRBase: chr14 :24,787,554-24,804,277
	TargetScan: NM_001198568
	cisRED: ENSG00000129467
Context	iHOP: ADCY4
	cancer metabolism search in PubMed: ADCY4
	UCL Cancer Institute: ADCY4
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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Phenotypic Information for ADCY4(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: ADCY4
	Familial Cancer Database: ADCY4

* 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 REACTOME_INTEGRATION_OF_ENERGY_METABOLISM

Others
OMIM	600292; gene.
Orphanet
Disease	KEGG Disease: ADCY4
	MedGen: ADCY4 (Human Medical Genetics with Condition)
	ClinVar: ADCY4
Phenotype	MGI: ADCY4 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: ADCY4

Mutations for ADCY4

* 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 ADCY4 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=70)	Stat. for Synonymous SNVs (# total SNVs=29)

Stat. for Deletions (# total SNVs=3)	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
chr14:24798609-24798609	p.R450W	3
chr14:24801072-24801072	p.R197R	2
chr14:24792231-24792231	p.E741K	2
chr14:24793378-24793378	p.L646L	2
chr14:24801108-24801108	p.N185N	2
chr14:24787653-24787653	p.R1068Q	2
chr14:24787905-24787905	p.N1012N	2
chr14:24787668-24787668	p.N1063S	2
chr14:24795358-24795358	p.R528fs*3	2
chr14:24787683-24787683	p.C1058F	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	5	2	1	13	3		3	2	2	1		10	4	3		1	12	9	1	10
# mutation	6	2	1	15	3		3	2	2	1		11	4	3		1	12	8	1	12
nonsynonymous SNV	3	2		11	1		3	1	1			8	4	2		1	3	6		11
synonymous SNV	3		1	4	2			1	1	1		3		1			9	2	1	1

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
chr14:24795366	p.R525H,ADCY4	3
chr14:24789026	p.S941F,ADCY4	2
chr14:24787668	p.N1063S,ADCY4	2
chr14:24798413	p.F885F,ADCY4	2
chr14:24788554	p.A460T,ADCY4	2
chr14:24791887	p.F203F,ADCY4	1
chr14:24798658	p.L1066F,ADCY4	1
chr14:24793338	p.F740L,ADCY4	1
chr14:24800479	p.T536P,ADCY4	1
chr14:24787904	p.N397N,ADCY4	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 ADCY4 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 ADCY4

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


ADCY4,ARHGEF15,AVPR2,CCM2L,CLEC14A,CXorf36,ECSCR, GPIHBP1,GPR146,KANK3,LRRC70,MMRN2,NOTCH4,PDE2A, PEAR1,ROBO4,S1PR1,SCARF1,TIE1,TPO,USHBP1	ADCY4,ARHGAP17,ARHGEF15,CCM2L,CXorf36,ESAM,FAM65A, FGD5,GNAZ,LRRC32,MMRN2,MYO7B,NOTCH4,NOVA2, PDE2A,ROBO4,SCARF1,SH2D3C,SHANK3,USHBP1,VWF

ADCY4,ARHGEF15,BCL6B,CCM2L,CD34,CLEC1A,CXorf36, ECSCR,ERG,FLI1,HSPA12B,KANK3,MMRN2,NOTCH4, PECAM1,S1PR1,SH2D3C,STARD8,TIE1,USHBP1,ZNF154	ADCY4,CLEC4GP1,CP,EFEMP1,FAM20A,GJA4,IRX5, ITIH4,JAG2,LOC90246,MBL1P,MEG3,MMP14,NOTCH4, PCOLCE,PLXND1,RAPGEF3,SCARF1,SFRP1,SHANK3,TIE1

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 ADCY4

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	ChEMBL	CHEMBL2097167; -.
Organism-specific databases	PharmGKB	PA24562; -.
Organism-specific databases	CTD	196883; -.

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
DB00938	adenylate cyclase 4	approved	Salmeterol

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Cross referenced IDs for ADCY4

* 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