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 PRKAR2A

Basic gene info.	Gene symbol	PRKAR2A
	Gene name	protein kinase, cAMP-dependent, regulatory, type II, alpha
	Synonyms	PKR2\|PRKAR2
	Cytomap	UCSC genome browser: 3p21.3-p21.2
	Genomic location	chr3 :48788092-48885270
	Type of gene	protein-coding
	RefGenes	NM_004157.2,
	Ensembl id	ENSG00000114302
	Description	cAMP-dependent protein kinase regulatory subunit RII alphacAMP-dependent protein kinase type II-alpha regulatory subunitprotein kinase A, RII-alpha subunit
	Modification date	20141207
dbXrefs	MIM : 176910
	HGNC : HGNC
	Ensembl : ENSG00000114302
	HPRD : 01484
	Vega : OTTHUMG00000133540
Protein	UniProt: P13861 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PRKAR2A
	BioGPS: 5576
	Gene Expression Atlas: ENSG00000114302
	The Human Protein Atlas: ENSG00000114302
Pathway	NCI Pathway Interaction Database: PRKAR2A
	KEGG: PRKAR2A
	REACTOME: PRKAR2A
	ConsensusPathDB
	Pathway Commons: PRKAR2A
Metabolism	MetaCyc: PRKAR2A
	HUMANCyc: PRKAR2A
Regulation	Ensembl's Regulation: ENSG00000114302
	miRBase: chr3 :48,788,092-48,885,270
	TargetScan: NM_004157
	cisRED: ENSG00000114302
Context	iHOP: PRKAR2A
	cancer metabolism search in PubMed: PRKAR2A
	UCL Cancer Institute: PRKAR2A
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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Phenotypic Information for PRKAR2A(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PRKAR2A
	Familial Cancer Database: PRKAR2A

* 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
REACTOME_INTEGRATION_OF_ENERGY_METABOLISM

Others
OMIM	176910; gene.
Orphanet
Disease	KEGG Disease: PRKAR2A
	MedGen: PRKAR2A (Human Medical Genetics with Condition)
	ClinVar: PRKAR2A
Phenotype	MGI: PRKAR2A (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PRKAR2A

Mutations for PRKAR2A

* 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

* 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	PRKAR2A	chr3	48798052	48798072		chr3	48597056	48597076
pancreas	PRKAR2A	chr3	48831942	48831962		chr3	48760161	48760181

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 PRKAR2A 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
AK299521	CTU2	1	664	16	88772911	88779212	PRKAR2A	656	1172	3	48785605	48786121
BG990796	PRKAR2A	21	234	3	48788257	48788469	MRPS5	228	322	2	95780958	95781052

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=24)	Stat. for Synonymous SNVs (# total SNVs=8)

Stat. for Deletions (# total SNVs=1)	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
chr3:48793865-48793865	p.D296N	3
chr3:48810487-48810487	p.Q199Q	2
chr3:48884918-48884918	p.T38P	1
chr3:48789714-48789714	p.E326K	1
chr3:48802507-48802507	p.S268L	1
chr3:48828036-48828036	p.Q126*	1
chr3:48789079-48789079	p.Y385C	1
chr3:48884962-48884962	p.R23Q	1
chr3:48793804-48793804	p.?	1
chr3:48810437-48810437	p.P216L	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=2

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	1		5			1					2		1			1	3	1	7
# mutation	2	1		5			1					2		1			1	3	1	7
nonsynonymous SNV	2	1		4								2		1			1	1	1	4
synonymous SNV				1			1											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
chr3:48810499	p.D136Y	1
chr3:48884962	p.S396N	1
chr3:48789046	p.E103E	1
chr3:48810501	p.Y385C	1
chr3:48789079	p.R93I	1
chr3:48810504	p.F367F	1
chr3:48789132	p.S80L	1
chr3:48820420	p.K358N	1
chr3:48789616	p.A72T	1
chr3:48820505	p.K358E	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 PRKAR2A 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 PRKAR2A

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


APPL1,ASXL2,BIRC6,CCNT1,CLOCK,DDI2,DPP8, EXOC6B,GTF2A1,PAFAH1B2,PBRM1,PPP4R2,PRKAR2A,RAD54L2, REST,SETD2,SON,STRN,UHMK1,VPRBP,ZNF106	AHCYL2,APOOL,ATE1,CUL4A,DMD,DPP8,HBS1L, HECTD1,HERC1,VWA8,KIF13A,LOC729082,LYRM7,MLXIP, PPTC7,PRKAR2A,PYGO1,UBE3C,UBR3,USO1,ZYG11B

ANAPC1,ASXL2,ATE1,DDI2,LATS1,LMBRD2,MAN2A1, NEU3,PDP2,PPP4R2,PRKAR2A,PTPLB,RAD54L2,RAPGEF6, RC3H2,REST,ROCK2,RSC1A1,SERINC5,STRN,TGFBRAP1	AQR,AVL9,C9orf129,DNAJA4,EYA3,FAM199X,FMN1, LMBRD2,MBNL3,MTMR8,NDUFS1,NHLRC2,PRKAR2A,PTPLB, SBNO1,SMC5,STRN,TMEM184C,UHMK1,UNC13B,ZDHHC20

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 PRKAR2A

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA33757; -.
Organism-specific databases	CTD	5576; -.

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
DB00125	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved; nutraceutical	L-Arginine
DB00155	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved; nutraceutical	L-Citrulline
DB00435	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved	Nitric Oxide
DB00988	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved	Dopamine
DB00171	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved; nutraceutical	Adenosine triphosphate
DB00770	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved; investigational	Alprostadil
DB00668	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved	Epinephrine
DB00131	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved; nutraceutical	Adenosine monophosphate
DB00396	protein kinase, cAMP-dependent, regulatory, type II, alpha	approved	Progesterone

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Cross referenced IDs for PRKAR2A

* 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