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 HMGCR

Basic gene info.	Gene symbol	HMGCR
	Gene name	3-hydroxy-3-methylglutaryl-CoA reductase
	Synonyms	LDLCQ3
	Cytomap	UCSC genome browser: 5q13.3-q14
	Genomic location	chr5 :74632992-74657926
	Type of gene	protein-coding
	RefGenes	NM_000859.2, NM_001130996.1,
	Ensembl id	ENSG00000113161
	Description	3-hydroxy-3-methylglutaryl CoA reductase (NADPH)3-hydroxy-3-methylglutaryl-Coenzyme A reductaseHMG-CoA reductasehydroxymethylglutaryl-CoA reductase
	Modification date	20141207
dbXrefs	MIM : 142910
	HGNC : HGNC
	Ensembl : ENSG00000113161
	HPRD : 00836
	Vega : OTTHUMG00000102069
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_HMGCR
	BioGPS: 3156
	Gene Expression Atlas: ENSG00000113161
	The Human Protein Atlas: ENSG00000113161
Pathway	NCI Pathway Interaction Database: HMGCR
	KEGG: HMGCR
	REACTOME: HMGCR
	ConsensusPathDB
	Pathway Commons: HMGCR
Metabolism	MetaCyc: HMGCR
	HUMANCyc: HMGCR
Regulation	Ensembl's Regulation: ENSG00000113161
	miRBase: chr5 :74,632,992-74,657,926
	TargetScan: NM_000859
	cisRED: ENSG00000113161
Context	iHOP: HMGCR
	cancer metabolism search in PubMed: HMGCR
	UCL Cancer Institute: HMGCR
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of HMGCR in cancer cell metabolism	1. 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)

Cancer 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/

Metabolic Pathway Description
REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM
Orphanet
Disease	KEGG Disease: HMGCR
	MedGen: HMGCR (Human Medical Genetics with Condition)
	ClinVar: HMGCR
Phenotype	MGI: HMGCR (International Mouse Phenotyping Consortium)
Phenotype	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.

Structural Variants in COSMIC : go to COSMIC mutation histogram

- Statistics for Tissue and Mutation type

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- 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'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
ovary	HMGCR	chr5	74639466	74639486		chr5	74579729	74579749
pancreas	HMGCR	chr5	74647500	74647520	HMGCR	chr5	74647426	74647446

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 HMGCR 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
DB238220	WDR41	1	348	5	76758920	76788045	HMGCR	349	584	5	74647342	74650477
BF853983	HMGCR	3	115	5	74657009	74657122	TP53INP2	113	214	20	33300042	33300143

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=2

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Somatic 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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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
chr5:74638449-74638449	p.R7G	2
chr5:74645924-74645924	p.Y205C	2
chr5:74654610-74654610	p.S705S	2
chr5:74655086-74655086	p.N750S	1
chr5:74640131-74640131	p.F113L	1
chr5:74646984-74646984	p.E345K	1
chr5:74650443-74650443	p.R495H	1
chr5:74655921-74655921	p.L857L	1
chr5:74643088-74643088	p.L170L	1
chr5:74651313-74651313	p.A616T	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	2		8			3		3			6	2	2		1	4	10		12
# mutation	1	2		8			3		3			5	2	2		1	7	11		15
nonsynonymous SNV	1	1		7			3		1			4	2	2			6	7		11
synonymous SNV		1		1					2			1				1	1	4		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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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
chr5:74646642	p.H270L,HMGCR	2
chr5:74641412	p.T751T,HMGCR	1
chr5:74651240	p.T119T,HMGCR	1
chr5:74655088	p.R300I,HMGCR	1
chr5:74646188	p.R537C,HMGCR	1
chr5:74647395	p.R787Q,HMGCR	1
chr5:74643031	p.F127L,HMGCR	1
chr5:74651260	p.S306F,HMGCR	1
chr5:74655094	p.G538G,HMGCR	1
chr5:74650434	p.G796V,HMGCR	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 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

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


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

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 HMGCR

Cross-referenced pharmacological DB IDs from Uniprot

DB Category

DB Name

DB's ID and Url link

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
DB00157	3-hydroxy-3-methylglutaryl-CoA reductase	approved; nutraceutical	NADH
DB00175	3-hydroxy-3-methylglutaryl-CoA reductase	approved	Pravastatin
DB00227	3-hydroxy-3-methylglutaryl-CoA reductase	approved; investigational	Lovastatin
DB00439	3-hydroxy-3-methylglutaryl-CoA reductase	withdrawn	Cerivastatin
DB00641	3-hydroxy-3-methylglutaryl-CoA reductase	approved	Simvastatin
DB01076	3-hydroxy-3-methylglutaryl-CoA reductase	approved	Atorvastatin
DB01095	3-hydroxy-3-methylglutaryl-CoA reductase	approved	Fluvastatin
DB01098	3-hydroxy-3-methylglutaryl-CoA reductase	approved	Rosuvastatin
DB01992	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	Coenzyme A
DB03431	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	Adenosine-5'-Diphosphate
DB03461	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	2'-Monophosphoadenosine 5'-Diphosphoribose
DB04377	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	3-Hydroxy-3-Methyl-Glutaric Acid
DB04447	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	1,4-Dithiothreitol
DB06693	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	Mevastatin
DB06846	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	7-[3-(4-FLUORO-PHENYL)-1-ISOPROPYL-1H-INDOL-2-YL]-3,5-DIHYDROXY-HEPTANOIC ACID
DB01907	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	Nicotinamide-Adenine-Dinucleotide
DB03518	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	(R)-Mevalonate
DB03785	3-hydroxy-3-methylglutaryl-CoA reductase	experimental	(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
DB00363	3-hydroxy-3-methylglutaryl-CoA reductase	approved	Clozapine
DB00502	3-hydroxy-3-methylglutaryl-CoA reductase	approved	Haloperidol
DB00264	3-hydroxy-3-methylglutaryl-CoA reductase	approved; investigational	Metoprolol

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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