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 PRKAR1A

Basic gene info.	Gene symbol	PRKAR1A
	Gene name	protein kinase, cAMP-dependent, regulatory, type I, alpha
	Synonyms	ACRDYS1\|ADOHR\|CAR\|CNC\|CNC1\|PKR1\|PPNAD1\|PRKAR1\|TSE1
	Cytomap	UCSC genome browser: 17q24.2
	Genomic location	chr17 :66508109-66528910
	Type of gene	protein-coding
	RefGenes	NM_001276289.1, NM_001276290.1,NM_001278433.1,NM_002734.4,NM_212471.2, NM_212472.2,
	Ensembl id	ENSG00000108946
	Description	Carney complex type 1cAMP-dependent protein kinase regulatory subunit RIalphacAMP-dependent protein kinase type I-alpha regulatory chaincAMP-dependent protein kinase type I-alpha regulatory subunitprotein kinase A type 1a regulatory subunittissue-spe
	Modification date	20141219
dbXrefs	MIM : 188830
	HGNC : HGNC
	Ensembl : ENSG00000108946
	HPRD : 01786
	Vega : OTTHUMG00000180128
Protein	UniProt: P10644 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PRKAR1A
	BioGPS: 5573
	Gene Expression Atlas: ENSG00000108946
	The Human Protein Atlas: ENSG00000108946
Pathway	NCI Pathway Interaction Database: PRKAR1A
	KEGG: PRKAR1A
	REACTOME: PRKAR1A
	ConsensusPathDB
	Pathway Commons: PRKAR1A
Metabolism	MetaCyc: PRKAR1A
	HUMANCyc: PRKAR1A
Regulation	Ensembl's Regulation: ENSG00000108946
	miRBase: chr17 :66,508,109-66,528,910
	TargetScan: NM_001276289
	cisRED: ENSG00000108946
Context	iHOP: PRKAR1A
	cancer metabolism search in PubMed: PRKAR1A
	UCL Cancer Institute: PRKAR1A
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of PRKAR1A in cancer cell metabolism	1. Robinson-White AJ, Bossis I, Hsiao H-P, Nesterova M, Leitner WW, et al. (2009) 8-Cl-adenosine inhibits proliferation and causes apoptosis in B-lymphocytes via protein kinase A-dependent and independent effects: implications for treatment of Carney complex-associated tumors. The Journal of Clinical Endocrinology & Metabolism 94: 4061-4069. go to article

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Phenotypic Information for PRKAR1A(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: PRKAR1A
	Familial Cancer Database: PRKAR1A

* 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	101800; phenotype. 160980; phenotype. 188830; gene. 255960; phenotype. 610489; phenotype.
Orphanet	1359; Carney complex. 189439; Primary pigmented nodular adrenocortical disease. 280651; Acrodysostosis with multiple hormone resistance. 520; Acute promyelocytic leukemia. 615; Familial atrial myxoma. 950; Acrodysostosis.
Disease	KEGG Disease: PRKAR1A
	MedGen: PRKAR1A (Human Medical Genetics with Condition)
	ClinVar: PRKAR1A
Phenotype	MGI: PRKAR1A (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PRKAR1A

Mutations for PRKAR1A

* 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 PRKAR1A 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
DA334350	PRKAR1A	3	285	17	66508618	66518922	FAM65C	286	595	20	49211470	49211779
EF428111	PRKAR1A	1	182	17	66511536	66511717	RARA	181	332	17	38504566	38504717
L03357	PRKAR1A	1	718	17	66511532	66522054	RET	717	1867	10	43612031	43622269
BF965634	PRKAR1A	1	661	17	66508578	66521095	RPS17L	652	740	15	83207056	83207655
EF428110	PRKAR1A	1	282	17	66511536	66518996	RARA	281	432	17	38504566	38504717
AV751006	TPP1	1	234	11	6635224	6635458	PRKAR1A	230	537	17	66527556	66527866
BI550151	NSL1	1	541	1	212964890	212977979	PRKAR1A	538	729	17	66526896	66527087
AA508561	PRKAR1A	1	111	17	66527867	66527977	PRKAR1A	108	188	17	66527926	66528006
CN478669	PRKAR1A	13	127	17	66528783	66528897	PRKAR1A	127	346	17	66528066	66528285

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=36)	Stat. for Synonymous SNVs (# total SNVs=9)

Stat. for Deletions (# total SNVs=5)	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
chr17:66518949-66518949	p.S77*	3
chr17:66522027-66522027	p.R228*	3
chr17:66526077-66526095	p.Q304fs*21	2
chr17:66526060-66526060	p.?	2
chr17:66524000-66524000	p.R243Q	2
chr17:66511684-66511684	p.M47fs*82	1
chr17:66524021-66524021	p.L250R	1
chr17:66519945-66519945	p.D143V	1
chr17:66526076-66526076	p.L303V	1
chr17:66511558-66511558	p.T6T	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=1

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	3		6			3		2			2	1					6		4
# mutation	1	3		8			3		2			2	1					6		4
nonsynonymous SNV	1	1		6			2		2			1	1					4		3
synonymous SNV		2		2			1					1						2		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
chr17:66519048	p.A7A,PRKAR1A	1
chr17:66525030	p.K222R,PRKAR1A	1
chr17:66511561	p.R13H,PRKAR1A	1
chr17:66519878	p.G225D,PRKAR1A	1
chr17:66525084	p.L15F,PRKAR1A	1
chr17:66511578	p.L250R,PRKAR1A	1
chr17:66519945	p.Y21Y,PRKAR1A	1
chr17:66526076	p.V253A,PRKAR1A	1
chr17:66511583	p.K24Q,PRKAR1A	1
chr17:66521096	p.S254C,PRKAR1A	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 PRKAR1A 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 PRKAR1A

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


AMZ2,APPBP2,BPTF,SMG8,CLCN3,CLTC,DCAF7, DHX40,DYNLL2,GNA13,HELZ,INTS2,LOC651250,MED13, NOL11,PRKAR1A,PSMD12,STXBP4,TLK2,TRIM37,VEZF1	ANKRD13C,BNIP2,C6orf120,CDC73,EPS15,EXOC5,FAM160B1, HCFC2,LUZP6,NCKAP1,OSBPL8,BLOC1S6,PRKAR1A,SERINC3, SHOC2,SMAD2,TBC1D23,TMED5,TMX3,TOR1AIP1,VAMP7

A4GNT,AMZ2,APPBP2,BCAR4,BPTF,CLTC,COX8C, CPS1,DZIP1L,GABRP,HELZ,LIPC,LOC100128239,LOC651250, PRKAR1A,RPS6KB1,SLC16A2,TANC2,TRIM61,USP32,YPEL2	ARMCX3,CEP170,EHBP1,IFT81,LBR,LRRK2,MTMR9, SLC9B2,NOVA1,NPAS3,NUCKS1,PBX3,PPFIBP1,PRKAR1A, PSIP1,QKI,RAB11FIP2,RBMS1,RIMKLB,SLC39A6,TCF4

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 PRKAR1A

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA33754; -.
Organism-specific databases	CTD	5573; -.

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
DB01790	protein kinase, cAMP-dependent, regulatory, type I, alpha	experimental	Sp-Adenosine-3',5'-Cyclic-Monophosphorothioate
DB02315	protein kinase, cAMP-dependent, regulatory, type I, alpha	experimental	Cyclic Guanosine Monophosphate
DB02527	protein kinase, cAMP-dependent, regulatory, type I, alpha	experimental	Cyclic Adenosine Monophosphate
DB00125	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved; nutraceutical	L-Arginine
DB00155	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved; nutraceutical	L-Citrulline
DB00435	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved	Nitric Oxide
DB00988	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved	Dopamine
DB00171	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved; nutraceutical	Adenosine triphosphate
DB00770	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved; investigational	Alprostadil
DB00668	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved	Epinephrine
DB00131	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved; nutraceutical	Adenosine monophosphate
DB00396	protein kinase, cAMP-dependent, regulatory, type I, alpha	approved	Progesterone

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Cross referenced IDs for PRKAR1A

* 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