Cancer Cell Metabolism Gene Database

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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 DPYD
Basic gene info.Gene symbolDPYD
Gene namedihydropyrimidine dehydrogenase
SynonymsDHP|DHPDHASE|DPD
CytomapUCSC genome browser: 1p22
Genomic locationchr1 :97543299-98386615
Type of geneprotein-coding
RefGenesNM_000110.3,
NM_001160301.1,
Ensembl idENSG00000188641
Descriptiondihydropyrimidine dehydrogenase [NADP(+)]dihydrothymine dehydrogenasedihydrouracil dehydrogenase
Modification date20141207
dbXrefs MIM : 612779
HGNC : HGNC
Ensembl : ENSG00000188641
HPRD : 02036
Vega : OTTHUMG00000039683
ProteinUniProt: Q12882
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_DPYD
BioGPS: 1806
Gene Expression Atlas: ENSG00000188641
The Human Protein Atlas: ENSG00000188641
PathwayNCI Pathway Interaction Database: DPYD
KEGG: DPYD
REACTOME: DPYD
ConsensusPathDB
Pathway Commons: DPYD
MetabolismMetaCyc: DPYD
HUMANCyc: DPYD
RegulationEnsembl's Regulation: ENSG00000188641
miRBase: chr1 :97,543,299-98,386,615
TargetScan: NM_000110
cisRED: ENSG00000188641
ContextiHOP: DPYD
cancer metabolism search in PubMed: DPYD
UCL Cancer Institute: DPYD
Assigned class in ccmGDBA - This gene has a literature evidence and it belongs to cancer gene.
References showing role of DPYD in cancer cell metabolism1. Metabolic rewiring is required for epithelial-mesenchymal transition. Cancer Discov 2014, 4: OF20. doi: 10.1158/2159-8290.CD-RW2014-190. go to article
2. Offer SM, Wegner NJ, Fossum C, Wang K, Diasio RB (2013) Phenotypic profiling of DPYD variations relevant to 5-fluorouracil sensitivity using real-time cellular analysis and in vitro measurement of enzyme activity. Cancer Res 73: 1958-1968. doi: 10.1158/0008-5472.CAN-12-3858. pmid: 3602211. go to article
3. Offer SM, Butterfield GL, Jerde CR, Fossum CC, Wegner NJ, et al. (2014) microRNAs miR-27a and miR-27b directly regulate liver dihydropyrimidine dehydrogenase expression through two conserved binding sites. Mol Cancer Ther 13: 742-751. doi: 10.1158/1535-7163.MCT-13-0878. pmid: 3954441. go to article
4. Shaul YD, Freinkman E, Comb WC, Cantor JR, Tam WL, et al. (2014) Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition. Cell 158: 1094-1109. doi: 10.1016/j.cell.2014.07.032. pmid: 4250222. go to article

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Phenotypic Information for DPYD(metabolism pathway, cancer, disease, phenome)
check002.gifCancer Description
Cancer CGAP: DPYD
Familial Cancer Database: DPYD
* 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_BETA_ALANINE_METABOLISM
KEGG_DRUG_METABOLISM_OTHER_ENZYMES
REACTOME_METABOLISM_OF_NUCLEOTIDES
REACTOME_PYRIMIDINE_METABOLISM

check002.gifOthers
OMIM 274270; phenotype.
274270; phenotype.
612779; gene.
612779; gene.
Orphanet 1675; Dihydropyrimidine dehydrogenase deficiency.
1675; Dihydropyrimidine dehydrogenase deficiency.
240839; 5-fluorouracil toxicity.
240839; 5-fluorouracil toxicity.
240855; Capecitabine toxicity.
240855; Capecitabine toxicity.
240955; Susceptibility to adverse reaction due to 5-fluorouracil treatment.
240955; Susceptibility to adverse reaction due to 5-fluorouracil treatment.
240963; Susceptibility to adverse reaction due to capecitabine treatment.
240963; Susceptibility to adverse reaction due to capecitabine treatment.
293948; 1p21.3 microdeletion syndrome.
293948; 1p21.3 microdeletion syndrome.
DiseaseKEGG Disease: DPYD
MedGen: DPYD (Human Medical Genetics with Condition)
ClinVar: DPYD
PhenotypeMGI: DPYD (International Mouse Phenotyping Consortium)
PhenomicDB: DPYD

Mutations for DPYD
* 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
* 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'.
SampleSymbol_aChr_aStart_aEnd_aSymbol_bChr_bStart_bEnd_b
breastDPYDchr19801275198012751IQSEC2chr235327822953278229
haematopoietic_and_lymphoid_tissueDPYDchr19761325597613255DPYDchr19759684697596846
ovaryDPYDchr19763404297634062AFF3chr2100567111100567131
ovaryDPYDchr19763447597634495DPYDchr19763457997634599
ovaryDPYDchr19768651097686530PTBP2chr19724224997242269
ovaryDPYDchr19771757297717592DPYDchr19825885698258876
ovaryDPYDchr19775858897758608DPYDchr19775402097754040
ovaryDPYDchr19775859197758611DPYDchr19775402397754043
ovaryDPYDchr19775859197758611INTS9chr82867703228677052
ovaryDPYDchr19788742897887448DPYDchr19788506197885081
ovaryDPYDchr19795695597956975DPYDchr19795701597957035
ovaryDPYDchr19798843297988452DPYDchr19824867698248696
pancreasDPYDchr19766253997662559DPYDchr19768721297687232
pancreasDPYDchr19766253997662559DPYDchr19768721797687237
pancreasDPYDchr19772635297726372DPYDchr19774044297740462
pancreasDPYDchr19783820397838223chr16617831466178334
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 DPYD related fusion information.
IDHead GeneTail Gene
AccessionGene_aqStart_aqEnd_aChromosome_atStart_atEnd_aGene_aqStart_aqEnd_aChromosome_atStart_atEnd_a
BG988212DPYD2030319812896798129251LOC100507373301622191428089014281216
BP319012DPYD135619832081898386590COX5B34543729826456598264657
CN412218DPYD48150219792952697929547KXD1496601191867004118670146
CV375938SRRM21921628047032804796DPYD8351619832214898322581
BI603836DPYD455019804881598049359NRIP35497501190025639002769
AB042557NBPF9111321144951765144994909DPYD1130115519795637597956402

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 # sample1     1 3 1  1  2
GAIN (# sample)1       2 1     2
LOSS (# sample)      1 2    1   
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=5

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check002.gifSomatic Mutation Counts per Tissue in COSMIC data
Stat. for Non-Synonymous SNVs
(# total SNVs=154)
Stat. for Synonymous SNVs
(# total SNVs=34)
Stat. for Deletions
(# total SNVs=0)
Stat. for Insertions
(# total SNVs=0)
There's no deleted snv.There's no inserted snv.

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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
chr1:98164976-98164976p.S204F4
chr1:97700485-97700485p.P789S4
chr1:97981340-97981340p.R561Q3
chr1:97847978-97847978p.D649Y3
chr1:98205983-98205983p.D96N3
chr1:97839164-97839164p.C671G3
chr1:98165013-98165013p.L192F3
chr1:98039426-98039426p.R410Q3
chr1:97544582-97544582p.P1010T3
chr1:97981407-97981407p.G539R3

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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=4

Point Mutation/ Tissue ID1234567891011121314151617181920
# sample51 392 10 3  1573 25317 15
# mutation61 442 12 3  21113 26120 20
nonsynonymous SNV5  352 8 2  1781 24712 19
synonymous SNV11 9  4 1  432  148 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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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
chr1:97658647p.S204F2
chr1:98039506p.I361I2
chr1:97839162p.N955N2
chr1:97700485p.A437V2
chr1:98348842p.R867L2
chr1:97981388p.C671C2
chr1:98205983p.D949N2
chr1:98058899p.E415K2
chr1:98039345p.L578F2
chr1:97547928p.R410Q2

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 DPYD 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 DPYD

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

ARAP2,C10orf128,CYBB,DPYD,FGL2,HLA-DRA,KCTD12,
LHFPL2,MCTP1,MPEG1,NCKAP1L,PIK3CG,PTAFR,RAB8B,
RGS18,SLC8A1,SLCO2B1,TFEC,TLR4,WIPF1,ZEB2
AKT3,ATP11C,BMPR2,BNIP2,CCDC82,CLIC4,DPYD,
EVI5,GABPA,KDSR,EFCAB14,OSBPL8,BLOC1S6,PRKAR1A,
PTPN12,RAB8B,SEPT10,SGMS1,SKAP2,TMX3,TRPC1

C3AR1,CMKLR1,CSF1,DPYD,HAVCR2,IL2RA,LAIR1,
LAPTM5,LCP2,LILRB1,MAFB,MS4A4A,MS4A6A,MYO5A,
NRP1,PDCD1LG2,PLEKHO2,SLAMF8,SLC15A3,STX11,TNFSF13B
PRR34,CA11,CDKN2C,CTSO,DISP1,DOCK11,DPYD,
FAM189B,LMO4,MCFD2,NAB2,NINJ1,P2RX7,PDE1B,
CPQ,SAP30,SCPEP1,SEC22C,SHF,SNX18,THOC5
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 DPYD
check002.gifCross-referenced pharmacological DB IDs from Uniprot
DB CategoryDB NameDB's ID and Url link
ChemistryBindingDB Q12882; -.
ChemistryChEMBL CHEMBL3172; -.
ChemistryBindingDB Q12882; -.
ChemistryChEMBL CHEMBL3172; -.
Organism-specific databasesPharmGKB PA145; -.
Organism-specific databasesPharmGKB PA145; -.
Organism-specific databasesCTD 1806; -.
Organism-specific databasesCTD 1806; -.

check002.gifDrug-Gene Interaction Network
* Gene Centered Interaction Network.
* Drug Centered Interaction Network.
DrugBank IDTarget NameDrug GroupsGeneric NameDrug Centered NetworkDrug Structure
DB02303dihydropyrimidine dehydrogenaseexperimental(5s)-5-Iododihydro-2,4(1h,3h)-Pyrimidinedione
DB02338dihydropyrimidine dehydrogenaseexperimentalNadph Dihydro-Nicotinamide-Adenine-Dinucleotidephosphate
DB03048dihydropyrimidine dehydrogenaseexperimental6-Carboxymethyluracil
DB03147dihydropyrimidine dehydrogenaseexperimentalFlavin-Adenine Dinucleotide
DB03247dihydropyrimidine dehydrogenaseexperimentalRiboflavin Monophosphate
DB03419dihydropyrimidine dehydrogenaseexperimentalUracil
DB03554dihydropyrimidine dehydrogenaseexperimental5-Iodouracil
DB01248dihydropyrimidine dehydrogenaseapproved; investigationalDocetaxel
DB00515dihydropyrimidine dehydrogenaseapprovedCisplatin
DB00650dihydropyrimidine dehydrogenaseapprovedLeucovorin
DB00526dihydropyrimidine dehydrogenaseapproved; investigationalOxaliplatin
DB00293dihydropyrimidine dehydrogenaseapproved; investigationalRaltitrexed
DB00563dihydropyrimidine dehydrogenaseapprovedMethotrexate
DB01101dihydropyrimidine dehydrogenaseapproved; investigationalCapecitabine
DB00762dihydropyrimidine dehydrogenaseapproved; investigationalIrinotecan
DB01033dihydropyrimidine dehydrogenaseapprovedMercaptopurine
DB00544dihydropyrimidine dehydrogenaseapprovedFluorouracil
DB01143dihydropyrimidine dehydrogenaseapproved; investigationalAmifostine
DB00958dihydropyrimidine dehydrogenaseapprovedCarboplatin
DB01229dihydropyrimidine dehydrogenaseapprovedPaclitaxel


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Cross referenced IDs for DPYD
* 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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