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 HMGCR
Basic gene info.Gene symbolHMGCR
Gene name3-hydroxy-3-methylglutaryl-CoA reductase
SynonymsLDLCQ3
CytomapUCSC genome browser: 5q13.3-q14
Genomic locationchr5 :74632992-74657926
Type of geneprotein-coding
RefGenesNM_000859.2,
NM_001130996.1,
Ensembl idENSG00000113161
Description3-hydroxy-3-methylglutaryl CoA reductase (NADPH)3-hydroxy-3-methylglutaryl-Coenzyme A reductaseHMG-CoA reductasehydroxymethylglutaryl-CoA reductase
Modification date20141207
dbXrefs MIM : 142910
HGNC : HGNC
Ensembl : ENSG00000113161
HPRD : 00836
Vega : OTTHUMG00000102069
ProteinUniProt:
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_HMGCR
BioGPS: 3156
Gene Expression Atlas: ENSG00000113161
The Human Protein Atlas: ENSG00000113161
PathwayNCI Pathway Interaction Database: HMGCR
KEGG: HMGCR
REACTOME: HMGCR
ConsensusPathDB
Pathway Commons: HMGCR
MetabolismMetaCyc: HMGCR
HUMANCyc: HMGCR
RegulationEnsembl's Regulation: ENSG00000113161
miRBase: chr5 :74,632,992-74,657,926
TargetScan: NM_000859
cisRED: ENSG00000113161
ContextiHOP: HMGCR
cancer metabolism search in PubMed: HMGCR
UCL Cancer Institute: HMGCR
Assigned class in ccmGDBA - This gene has a literature evidence and it belongs to cancer gene.
References showing role of HMGCR in cancer cell metabolism1. Sangeetha M, Deepa PR, Rishi P, Khetan V, Krishnakumar S (2015) Global Gene Deregulations in FASN Silenced Retinoblastoma Cancer Cells: Molecular and Clinico-Pathological Correlations. J Cell Biochem. doi: 10.1002/jcb.25217. go to article
2. Zhang H, Feng Z, Huang R, Xia Z, Xiang G, et al. (2014) MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade lipid metabolic pathway related to SIRT1. Int J Oncol 45: 2143-2152. doi: 10.3892/ijo.2014.2596. go to article
3. Pandyra A, Mullen PJ, Kalkat M, Yu R, Pong JT, et al. (2014) Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. Cancer Res 74: 4772-4782. doi: 10.1158/0008-5472.CAN-14-0130. go to article
4. Yeganeh B, Wiechec E, Ande SR, Sharma P, Moghadam AR, et al. (2014) Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease. Pharmacol Ther 143: 87-110. doi: 10.1016/j.pharmthera.2014.02.007. pmid: 4005604. go to article

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

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

Mutations for HMGCR
* 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
* 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
ovaryHMGCRchr57463946674639486chr57457972974579749
pancreasHMGCRchr57464750074647520HMGCRchr57464742674647446
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 HMGCR related fusion information.
IDHead GeneTail Gene
AccessionGene_aqStart_aqEnd_aChromosome_atStart_atEnd_aGene_aqStart_aqEnd_aChromosome_atStart_atEnd_a
DB238220WDR41134857675892076788045HMGCR34958457464734274650477
BF853983HMGCR311557465700974657122TP53INP2113214203330004233300143

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
There's no copy number variation information in COSMIC data for this gene.

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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=2

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check002.gifSomatic Mutation Counts per Tissue in COSMIC data
Stat. for Non-Synonymous SNVs
(# total SNVs=49)
Stat. for Synonymous SNVs
(# total SNVs=13)
Stat. for Deletions
(# total SNVs=2)
Stat. for Insertions
(# total SNVs=0)
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
chr5:74638449-74638449p.R7G2
chr5:74645924-74645924p.Y205C2
chr5:74654610-74654610p.S705S2
chr5:74652176-74652176p.R630L1
chr5:74646188-74646188p.K257E1
chr5:74647030-74647030p.T360K1
chr5:74655094-74655094p.A753S1
chr5:74641412-74641412p.F127L1
chr5:74650518-74650518p.S520F1
chr5:74652209-74652209p.R641H1

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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=1

Point Mutation/ Tissue ID1234567891011121314151617181920
# sample12 8  3 3  622 1410 12
# mutation12 8  3 3  522 1711 15
nonsynonymous SNV11 7  3 1  422  67 11
synonymous SNV 1 1    2  1   114 4
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
chr5:74646642p.H270L,HMGCR2
chr5:74638511p.E550D1
chr5:74650443p.A700S,HMGCR1
chr5:74651313p.G96C,HMGCR1
chr5:74643075p.S527R,HMGCR1
chr5:74655281p.Q713R,HMGCR1
chr5:74646703p.G96D,HMGCR1
chr5:74638514p.P277A,HMGCR1
chr5:74650486p.G534W,HMGCR1
chr5:74651335p.P733L,HMGCR1

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 HMGCR 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 HMGCR

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

AADAC,AMHR2,C1orf141,FOXL2NB,MGARP,CELA2A,CYP11A1,
CYP17A1,CYP19A1,FSHR,HMGCR,HSD3B1,HSD3B2,INHA,
KLHL4,LHCGR,MBOAT4,MRO,STAR,TCF21,TREML5P
ABCC11,ABCC2,ACSL3,AFMID,AKR1D1,ALOX15B,B3GAT1,
C6orf223,CCDC15,GSTT2,HMGCR,HMGCS1,MPV17L,NSUN2,
PXMP4,MSMO1,SLC5A11,SLCO1B1,SRD5A1,TARP,ZP2

ACAT2,ACSL3,AP3B1,CYP51A1,DHCR24,DHCR7,ELOVL6,
FDFT1,FDPS,HMGCR,HMGCS1,HSD17B7,IDI1,LSS,
MVD,MVK,PANK3,PCSK9,MSMO1,SC5D,STARD4
ACTR2,AP1G1,APAF1,BAZ1A,CCDC186,CLTC,CTTNBP2NL,
CYP51A1,DHCR24,FAM199X,FDFT1,FNDC3B,GAN,GPD2,
HMGCR,KDM1B,LOC284441,PGGT1B,RRBP1,TOP1,YME1L1
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 HMGCR
check002.gifCross-referenced pharmacological DB IDs from Uniprot
DB CategoryDB NameDB's ID and Url link

check002.gifDrug-Gene Interaction Network
* Gene Centered Interaction Network.
* Drug Centered Interaction Network.
DrugBank IDTarget NameDrug GroupsGeneric NameDrug Centered NetworkDrug Structure
DB001573-hydroxy-3-methylglutaryl-CoA reductaseapproved; nutraceuticalNADH
DB001753-hydroxy-3-methylglutaryl-CoA reductaseapprovedPravastatin
DB002273-hydroxy-3-methylglutaryl-CoA reductaseapproved; investigationalLovastatin
DB004393-hydroxy-3-methylglutaryl-CoA reductasewithdrawnCerivastatin
DB006413-hydroxy-3-methylglutaryl-CoA reductaseapprovedSimvastatin
DB010763-hydroxy-3-methylglutaryl-CoA reductaseapprovedAtorvastatin
DB010953-hydroxy-3-methylglutaryl-CoA reductaseapprovedFluvastatin
DB010983-hydroxy-3-methylglutaryl-CoA reductaseapprovedRosuvastatin
DB019923-hydroxy-3-methylglutaryl-CoA reductaseexperimentalCoenzyme A
DB034313-hydroxy-3-methylglutaryl-CoA reductaseexperimentalAdenosine-5'-Diphosphate
DB034613-hydroxy-3-methylglutaryl-CoA reductaseexperimental2'-Monophosphoadenosine 5'-Diphosphoribose
DB043773-hydroxy-3-methylglutaryl-CoA reductaseexperimental3-Hydroxy-3-Methyl-Glutaric Acid
DB044473-hydroxy-3-methylglutaryl-CoA reductaseexperimental1,4-Dithiothreitol
DB066933-hydroxy-3-methylglutaryl-CoA reductaseexperimentalMevastatin
DB068463-hydroxy-3-methylglutaryl-CoA reductaseexperimental7-[3-(4-FLUORO-PHENYL)-1-ISOPROPYL-1H-INDOL-2-YL]-3,5-DIHYDROXY-HEPTANOIC ACID
DB019073-hydroxy-3-methylglutaryl-CoA reductaseexperimentalNicotinamide-Adenine-Dinucleotide
DB035183-hydroxy-3-methylglutaryl-CoA reductaseexperimental(R)-Mevalonate
DB037853-hydroxy-3-methylglutaryl-CoA reductaseexperimental(3r,5r)-7-((1r,2r,6s,8r,8as)-2,6-Dimethyl-8-{[(2r)-2-Methylbutanoyl]Oxy}-1,2,6,7,8,8a-Hexahydronaphthalen-1-Yl)-3,5-Dihydroxyheptanoic Acid
DB003633-hydroxy-3-methylglutaryl-CoA reductaseapprovedClozapine
DB005023-hydroxy-3-methylglutaryl-CoA reductaseapprovedHaloperidol
DB002643-hydroxy-3-methylglutaryl-CoA reductaseapproved; investigationalMetoprolol


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Cross referenced IDs for HMGCR
* 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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