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 INS

Basic gene info.	Gene symbol	INS
	Gene name	insulin
	Synonyms	IDDM\|IDDM1\|IDDM2\|ILPR\|IRDN\|MODY10
	Cytomap	UCSC genome browser: 11p15.5
	Genomic location	chr11 :2181008-2182439
	Type of gene	protein-coding
	RefGenes	NM_000207.2, NM_001185097.1,NM_001185098.1,NM_001291897.1,
	Ensembl id	ENSG00000254647
	Description	preproinsulinproinsulin
	Modification date	20141222
dbXrefs	MIM : 176730
	HGNC : HGNC
	Ensembl : ENSG00000254647
	HPRD : 01455
	Vega : OTTHUMG00000009558
Protein	UniProt: P01308 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_INS
	BioGPS: 3630
	Gene Expression Atlas: ENSG00000254647
	The Human Protein Atlas: ENSG00000254647
Pathway	NCI Pathway Interaction Database: INS
	KEGG: INS
	REACTOME: INS
	ConsensusPathDB
	Pathway Commons: INS
Metabolism	MetaCyc: INS
	HUMANCyc: INS
Regulation	Ensembl's Regulation: ENSG00000254647
	miRBase: chr11 :2,181,008-2,182,439
	TargetScan: NM_000207
	cisRED: ENSG00000254647
Context	iHOP: INS
	cancer metabolism search in PubMed: INS
	UCL Cancer Institute: INS
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of INS in cancer cell metabolism	1. Lin LL, Huang HC, Juan HF, Taida Cancer Systems Biology Study G (2015) Circadian systems biology in Metazoa. Brief Bioinform. doi: 10.1093/bib/bbv006. go to article 2. Ferroni P, Riondino S, Buonomo O, Palmirotta R, Guadagni F, et al. (2015) Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress. Oxid Med Cell Longev 2015: 183928. doi: 10.1155/2015/183928. pmid: 4480937. go to article 3. Feitelson MA, Arzumanyan A, Kulathinal RJ, Blain SW, Holcombe RF, et al. (2015) Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. Semin Cancer Biol. doi: 10.1016/j.semcancer.2015.02.006. go to article

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

Cancer Description
Cancer	CGAP: INS
	Familial Cancer Database: INS

* 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_INTEGRATION_OF_ENERGY_METABOLISM

Others
OMIM	125852; phenotype. 176730; gene+phenotype. 606176; phenotype. 613370; phenotype.
Orphanet	552; MODY syndrome. 99885; Permanent neonatal diabetes mellitus.
Disease	KEGG Disease: INS
	MedGen: INS (Human Medical Genetics with Condition)
	ClinVar: INS
Phenotype	MGI: INS (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: INS

Mutations for INS

* 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

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

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows INS 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
BC148488	IGF2	33	220	11	2129117	2149603	INS	221	640	11	2159779	2161209
BC153083	IGF2	33	220	11	2129117	2149603	INS	221	640	11	2159779	2161209

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=8)	Stat. for Synonymous SNVs (# total SNVs=5)

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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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
chr11:2182073-2182073	p.C43C	2
chr11:2181169-2181169	p.L82L	1
chr11:2181187-2181187	p.S76R	1
chr11:2182027-2182027	p.E59K	1
chr11:2182069-2182069	p.E45K	1
chr11:2182081-2182081	p.L41L	1
chr11:2181082-2181082	p.111	1
chr11:2182097-2182097	p.L35L	1
chr11:2181097-2181097	p.E106D	1
chr11:2182108-2182108	p.G32R	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					2							1								2
# mutation					2							1								2
nonsynonymous SNV					1															1
synonymous SNV					1							1								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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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
chr11:2181082	p.X111X,INS	1
chr11:2181097	p.E106D,INS	1
chr11:2181139	p.V92V,INS	1
chr11:2181169	p.L82L,INS	1
chr11:2181187	p.S76R,INS	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 INS 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 INS

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


CGB,CGB1,CGB5,CGB8,FAM47C,FFAR2,GCG, GSDMB,INS,LOC727924,LINC00052,OR4M2,OR4N2,OR4N3P, OR4N4,OR4Q3,PWAR4___F2RL3___PAWR,PPY,SNORD115-26,TEX28,TTR	NA,NA,NA,NA,NA,NA,NA, NA,NA,NA,NA,NA,NA,NA, NA,NA,NA,NA,NA,NA,NA

ADAM5,AGT,ALDH1A1,CACNA1B,CALML6,CLCNKA,DPPA2, FAM198B,IAPP,IFNL2,INS,CFAP74,LOC388428,OBSCN, PRSS50,PVT1,RASL10B,SLC17A9,SNORA16A,SPAG17,USP17L6P	NA,NA,NA,NA,NA,NA,NA, NA,NA,NA,NA,NA,NA,NA, NA,NA,NA,NA,NA,NA,NA

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 INS

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	ChEMBL	CHEMBL5881; -.
Organism-specific databases	PharmGKB	PA201; -.
Organism-specific databases	CTD	3630; -.

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
DB01776	insulin	experimental	M-Cresol
DB08231	insulin	experimental	MYRISTIC ACID
DB00121	insulin	approved; nutraceutical	Biotin
DB00877	insulin	approved; investigational	Sirolimus
DB00122	insulin	approved; nutraceutical	Choline

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Cross referenced IDs for INS

* 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