Cancer Cell Metabolism Gene Database

  Cancer Cell Metabolism Gene DB

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Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

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 CAD
Basic gene info.Gene symbolCAD
Gene namecarbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
Synonyms-
CytomapUCSC genome browser: 2p22-p21
Genomic locationchr2 :27440257-27466654
Type of geneprotein-coding
RefGenesNM_004341.3,
Ensembl idENSG00000084774
DescriptionCAD proteinCAD trifunctional proteinmultifunctional protein CAD
Modification date20141207
dbXrefs MIM : 114010
HGNC : HGNC
Ensembl : ENSG00000084774
HPRD : 06437
Vega : OTTHUMG00000097070
ProteinUniProt: P27708
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_CAD
BioGPS: 790
Gene Expression Atlas: ENSG00000084774
The Human Protein Atlas: ENSG00000084774
PathwayNCI Pathway Interaction Database: CAD
KEGG: CAD
REACTOME: CAD
ConsensusPathDB
Pathway Commons: CAD
MetabolismMetaCyc: CAD
HUMANCyc: CAD
RegulationEnsembl's Regulation: ENSG00000084774
miRBase: chr2 :27,440,257-27,466,654
TargetScan: NM_004341
cisRED: ENSG00000084774
ContextiHOP: CAD
cancer metabolism search in PubMed: CAD
UCL Cancer Institute: CAD
Assigned class in ccmGDBA - This gene has a literature evidence and it belongs to cancer gene.
References showing role of CAD in cancer cell metabolism1. Sharma A, Janocha AJ, Hill BT, Smith MR, Erzurum SC, et al. (2014) Targeting mTORC1-mediated metabolic addiction overcomes fludarabine resistance in malignant B cells. Mol Cancer Res 12: 1205-1215. doi: 10.1158/1541-7786.MCR-14-0124. pmid: 4163513. go to article
2. Morin A, Fritsch L, Mathieu JR, Gilbert C, Guarmit B, et al. (2012) Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence. FASEB J 26: 460-467. doi: 10.1096/fj.11-191296. go to article
3. Makinoshima H, Takita M, Matsumoto S, Yagishita A, Owada S, et al. (2014) Epidermal growth factor receptor (EGFR) signaling regulates global metabolic pathways in EGFR-mutated lung adenocarcinoma. J Biol Chem 289: 20813-20823. doi: 10.1074/jbc.M114.575464. pmid: 4110289. go to article
4. Graves LM, Guy HI, Kozlowski P, Huang M, Lazarowski E, et al. (2000) Regulation of carbamoyl phosphate synthetase by MAP kinase. Nature 403: 328-332. doi: 10.1038/35002111. go to article

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Phenotypic Information for CAD(metabolism pathway, cancer, disease, phenome)
check002.gifCancer Description
Cancer CGAP: CAD
Familial Cancer Database: CAD
* 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/

check002.gifMetabolic Pathway Description
KEGG_PYRIMIDINE_METABOLISM
KEGG_ALANINE_ASPARTATE_AND_GLUTAMATE_METABOLISM
REACTOME_METABOLISM_OF_NUCLEOTIDES
REACTOME_PYRIMIDINE_METABOLISM

check002.gifOthers
OMIM 114010; gene.
Orphanet
DiseaseKEGG Disease: CAD
MedGen: CAD (Human Medical Genetics with Condition)
ClinVar: CAD
PhenotypeMGI: CAD (International Mouse Phenotyping Consortium)
PhenomicDB: CAD

Mutations for CAD
* 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.

check002.gifStructural Variants in COSMIC: go to COSMIC mutation histogram

- Statistics for Tissue and Mutation typeTop
- For Inter-chromosomal Variations
There's no inter-chromosomal structural variation.
- For Intra-chromosomal Variations
There's no intra-chromosomal structural variation.
SampleSymbol_aChr_aStart_aEnd_aSymbol_bChr_bStart_bEnd_b
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)

check002.gifRelated fusion transcripts : go to Chitars2.0
* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows CAD related fusion information.
IDHead GeneTail Gene
AccessionGene_aqStart_aqEnd_aChromosome_atStart_atEnd_aGene_aqStart_aqEnd_aChromosome_atStart_atEnd_a
CN265854CAD15622746377827463935CKAP549133114676509246765176
BF765434FOXK21210178055950780559716CAD20232722745962227460295

check002.gifOther DBs for Structural Variants
Structural Variants in Ensembl: go to Ensembl Structural variation
Structural Variants in dbVar: go to dbVar

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check002.gifCopy Number Variations in COSMIC: go to COSMIC mutation CNV/Expr
 
Mutation type/ Tissue IDbrcacnscervendomehaematopokidnLintestliverlungnsovarypancreprostskinstomathyrourina
Total # sample   1             
GAIN (# sample)   1             
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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check002.gifSNV 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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check002.gifSomatic Mutation Counts per Tissue in COSMIC data
Stat. for Non-Synonymous SNVs
(# total SNVs=166)
Stat. for Synonymous SNVs
(# total SNVs=53)
Stat. for Deletions
(# total SNVs=5)
Stat. for Insertions
(# total SNVs=1)

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check002.gifTop 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 positionMutation(aa)Unique sampleID count
chr2:27460721-27460721p.R1567W4
chr2:27456204-27456204p.E1006*3
chr2:27465263-27465263p.R2064C3
chr2:27465748-27465748p.F2129F3
chr2:27445851-27445851p.C252F3
chr2:27462633-27462633p.P1821P2
chr2:27457482-27457482p.T1239A2
chr2:27454397-27454397p.V783V2
chr2:27455332-27455332p.R888C2
chr2:27459689-27459689p.R1463*2

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check002.gifSNV 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 ID1234567891011121314151617181920
# sample692265 4 42121157 12220 22
# mutation792265 4 42126147 12821 33
nonsynonymous SNV682163 2 32 19126 11314 22
synonymous SNV11 102 2 1 1721  157 11
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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check002.gifTop 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 PositionMutation(aa)Unique sampleID count
chr2:27460681p.A1553A3
chr2:27465619p.T585S2
chr2:27465748p.F2118F2
chr2:27447254p.F2129F2
chr2:27447965p.T1239A2
chr2:27465263p.E347K2
chr2:27455482p.G492W2
chr2:27446828p.L938F2
chr2:27456970p.A1165V2
chr2:27457482p.R2064C2

check002.gifOther 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

check002.gifCopy Number for CAD 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 CAD

check002.gifGene 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.

check002.gifDifferential 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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check002.gifCNV 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
check002.gifCo-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

AGBL5,CAD,CENPA,CENPO,GART,GPN1,GTF3C2,
ILF3,INCENP,MPP6,MSH2,MSH6,ORC1,PLK1,
POLR1A,RNASEH1,RRP1B,SKP2,UBXN2A,WDR43,YEATS2
PRRC2A,CABIN1,CAD,CD3EAP,DNMT1,ICOSLG,ILF3,
KDM5C,MYBBP1A,NAT10,NCAPD2,PDCD11,PFAS,PLXNB2,
PTK7,RAI1,RCC2,TCF3,ZBTB12,ZNF512B,ZNF74

ANAPC1,PRRC2A,CAD,DHX57,GTF3C2,ILF3,ING5,
KIAA1958,MDN1,NCL,PDCD11,POLR1A,POLR1B,RIF1,
SMPD4,SNRNP200,TGFBRAP1,TTLL4,WDR33,XPO5,ZNF142
PRRC2A,BMS1,C2CD3,CAD,CKAP5,GCN1L1,ILF3,
LARP1,MDC1,MYBBP1A,NUP188,PDCD11,PFAS,POLR1A,
PRKDC,RBM19,RPAP1,TCHP,URB1,XPO5,ZC3H18
check002.gifCo-Expressed gene's Protein-protein interaction 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

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check002.gifInteracting 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 CAD
check002.gifCross-referenced pharmacological DB IDs from Uniprot
DB CategoryDB NameDB's ID and Url link
ChemistryBindingDB P27708; -.
ChemistryChEMBL CHEMBL3093; -.
Organism-specific databasesPharmGKB PA26023; -.
Organism-specific databasesCTD 790; -.

check002.gifDrug-Gene Interaction Network
* Gene Centered Interaction Network.
* Drug Centered Interaction Network.
DrugBank IDTarget NameDrug GroupsGeneric NameDrug Centered NetworkDrug Structure
DB00128carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotaseapproved; nutraceuticalL-Aspartic Acid
DB03459carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotaseexperimentalN-(Phosphonacetyl)-L-Aspartic Acid
DB00130carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotaseapproved; nutraceutical; investigationalL-Glutamine


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Cross referenced IDs for CAD
* 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



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