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 CP

Basic gene info.	Gene symbol	CP
	Gene name	ceruloplasmin (ferroxidase)
	Synonyms	CP-2
	Cytomap	UCSC genome browser: 3q23-q25
	Genomic location	chr3 :148880196-148939832
	Type of gene	protein-coding
	RefGenes	NM_000096.3, NR_046371.1,
	Ensembl id	ENSG00000047457
	Description	ceruloplasmin
	Modification date	20141219
dbXrefs	MIM : 117700
	HGNC : HGNC
	Ensembl : ENSG00000047457
	HPRD : 00317
	Vega : OTTHUMG00000159563
Protein	UniProt: P00450 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_CP
	BioGPS: 1356
	Gene Expression Atlas: ENSG00000047457
	The Human Protein Atlas: ENSG00000047457
Pathway	NCI Pathway Interaction Database: CP
	KEGG: CP
	REACTOME: CP
	ConsensusPathDB
	Pathway Commons: CP
Metabolism	MetaCyc: CP
	HUMANCyc: CP
Regulation	Ensembl's Regulation: ENSG00000047457
	miRBase: chr3 :148,880,196-148,939,832
	TargetScan: NM_000096
	cisRED: ENSG00000047457
Context	iHOP: CP
	cancer metabolism search in PubMed: CP
	UCL Cancer Institute: CP
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of CP in cancer cell metabolism	1. Lokamani I, Looi ML, Md Ali SA, Mohd Dali AZ, Ahmad Annuar MA, et al. (2014) Gelsolin and ceruloplasmin as potential predictive biomarkers for cervical cancer by 2D-DIGE proteomics analysis. Pathol Oncol Res 20: 119-129. doi: 10.1007/s12253-013-9670-9. go to article 2. Babich PS, Skvortsov AN, Rusconi P, Tsymbalenko NV, Mutanen M, et al. (2013) Non-hepatic tumors change the activity of genes encoding copper trafficking proteins in the liver. Cancer Biol Ther 14: 614-624. doi: 10.4161/cbt.24594. pmid: 3742491. go to article

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

Cancer Description
Cancer	CGAP: CP
	Familial Cancer Database: CP

* 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_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM

Others
OMIM	117700; gene. 604290; phenotype.
Orphanet	48818; Aceruloplasminemia.
Disease	KEGG Disease: CP
	MedGen: CP (Human Medical Genetics with Condition)
	ClinVar: CP
Phenotype	MGI: CP (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: CP

Mutations for CP

* 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
breast	CP	chr3	148913662	148913662	CP	chr3	148921377	148921377
ovary	CP	chr3	148901465	148901485	PHF16	chr23	46843716	46843736
ovary	CP	chr3	148914523	148914543	CP	chr3	148921744	148921764
ovary	CP	chr3	148925430	148925450		chr3	149063055	149063075

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 CP 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

BG945303

ATXN7

436

63950706

63951571

434

453

148911232

148911251

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=7

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=96)	Stat. for Synonymous SNVs (# total SNVs=24)

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
chr3:148927028-148927028	p.E251K	7
chr3:148939579-148939579	p.?	4
chr3:148927989-148927989	p.S191*	3
chr3:148939490-148939490	p.E30D	3
chr3:148927978-148927978	p.G195R	2
chr3:148924112-148924112	p.F351L	2
chr3:148923985-148923985	p.F393S	2
chr3:148916180-148916180	p.G563R	2
chr3:148928058-148928058	p.G168A	2
chr3:148897410-148897410	p.S865F	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=4

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	2	14	5		4		2	2		8	8	2		1	14	9		17
# mutation	1	6	2	17	5		4		2	2		8	8	2		1	15	13		19
nonsynonymous SNV	1	3	2	13	5		4		1	2		7	3	1		1	11	8		14
synonymous SNV		3		4					1			1	5	1			4	5		5

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
chr3:148927028	p.E251K	4
chr3:148927978	p.D103D	2
chr3:148928050	p.G708D	2
chr3:148897410	p.G195R	2
chr3:148903188	p.D171N	2
chr3:148930323	p.S865F	2
chr3:148928058	p.G168V	2
chr3:148899805	p.K128N	1
chr3:148917539	p.F920F	1
chr3:148928098	p.N762T	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 CP 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 CP

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


ACADM,ALDH6A1,ATPAF1,BSDC1,C1orf210,TCEANC2,CPT2, DHCR24,IPP,IVD,KIAA0319L,MYCBP,NRD1,NSUN4, OMA1,PAFAH2,PARS2,POMGNT1,SCP2,TMEM59,YIPF1	ABCB6,ACADM,AIFM1,MPC2,C19orf54,GUCD1,COQ6, CPT2,CRAT,CSPG5,DBI,GRPEL1,HIST1H1C,IVD, LDHD,NDUFA10,NDUFAF1,NFS1,PCCB,ECI2,SUOX

ABCD3,ACADS,ALDH6A1,ARHGEF16,C1orf210,CPT2,DLST, ETFDH,GGT6,GPBP1L1,HMGCL,LDHD,NUDT6,OMA1, PAFAH2,PIGR,RBM47,RPS6KA1,SCP2,SIAE,TMEM125	ACSF2,AGFG2,AP1M2,BDH1,CPT2,DTX4,ENTPD5, EPB41L4B,KLF5,LDLRAP1,MARVELD3,MYO1D,PAFAH2,PLD1, PPARG,PTK6,SFXN5,SH3BGRL2,SLC44A1,TRAF3IP2,WDR78

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 CP

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA26815; -.
Organism-specific databases	CTD	1356; -.

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
DB01033	ceruloplasmin (ferroxidase)	approved	Mercaptopurine
DB00563	ceruloplasmin (ferroxidase)	approved	Methotrexate

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Cross referenced IDs for CP

* 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