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 CLOCK

Basic gene info.	Gene symbol	CLOCK
	Gene name	clock circadian regulator
	Synonyms	KAT13D\|bHLHe8
	Cytomap	UCSC genome browser: 4q12
	Genomic location	chr4 :56298659-56412997
	Type of gene	protein-coding
	RefGenes	NM_001267843.1, NM_004898.3,
	Ensembl id	ENSG00000134852
	Description	circadian locomoter output cycles kaput proteincircadian locomoter output cycles protein kaputclass E basic helix-loop-helix protein 8clock homolog
	Modification date	20141222
dbXrefs	MIM : 601851
	HGNC : HGNC
	Ensembl : ENSG00000134852
	HPRD : 03508
	Vega : OTTHUMG00000102141
Protein	UniProt: O15516 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_CLOCK
	BioGPS: 9575
	Gene Expression Atlas: ENSG00000134852
	The Human Protein Atlas: ENSG00000134852
Pathway	NCI Pathway Interaction Database: CLOCK
	KEGG: CLOCK
	REACTOME: CLOCK
	ConsensusPathDB
	Pathway Commons: CLOCK
Metabolism	MetaCyc: CLOCK
	HUMANCyc: CLOCK
Regulation	Ensembl's Regulation: ENSG00000134852
	miRBase: chr4 :56,298,659-56,412,997
	TargetScan: NM_001267843
	cisRED: ENSG00000134852
Context	iHOP: CLOCK
	cancer metabolism search in PubMed: CLOCK
	UCL Cancer Institute: CLOCK
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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

Cancer Description
Cancer	CGAP: CLOCK
	Familial Cancer Database: CLOCK

* 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	601851; gene.
Orphanet
Disease	KEGG Disease: CLOCK
	MedGen: CLOCK (Human Medical Genetics with Condition)
	ClinVar: CLOCK
Phenotype	MGI: CLOCK (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: CLOCK

Mutations for CLOCK

* 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

* 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'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
ovary	CLOCK	chr4	56306510	56306530	CLOCK	chr4	56352273	56352293
ovary	CLOCK	chr4	56318273	56318293		chr8	75768627	75768647
pancreas	CLOCK	chr4	56311262	56311282	CLOCK	chr4	56311434	56311454
pancreas	CLOCK	chr4	56311386	56311406	CLOCK	chr4	56316157	56316177

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 CLOCK related fusion information.

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

BE883242

CLOCK

56299576

56299645

CLOCK

676

56299008

56299610

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

Mutation type/ Tissue ID

brca

cns

cerv

endome

haematopo

kidn

Lintest

liver

lung

ovary

pancre

prost

skin

stoma

thyro

urina

Total # sample

GAIN (# sample)

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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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=57)	Stat. for Synonymous SNVs (# total SNVs=10)

Stat. for Deletions (# total SNVs=18)	Stat. for Insertions (# total SNVs=4)

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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
chr4:56336954-56336954	p.L123fs*1	17
chr4:56336953-56336954	p.L123fs*14	3
chr4:56325088-56325088	p.V255I	2
chr4:56315604-56315604	p.H470Y	2
chr4:56315615-56315615	p.H466L	2
chr4:56336906-56336906	p.T139N	2
chr4:56348941-56348941	p.T4T	2
chr4:56304455-56304455	p.F785L	2
chr4:56304599-56304599	p.A737A	1
chr4:56316339-56316339	p.R423G	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			7	5		4		2	1		3	4	1		1	1	3		7
# mutation	1			9	5		4		2	1		3	4	1		1	1	4		9
nonsynonymous SNV	1			7	3		3		2			3	4	1			1	3		8
synonymous SNV				2	2		1			1						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
chr4:56308750	p.Q652K,CLOCK	2
chr4:56304676	p.G673R,CLOCK	1
chr4:56345063	p.T240A,CLOCK	1
chr4:56315025	p.S19G,CLOCK	1
chr4:56325372	p.R239H,CLOCK	1
chr4:56308641	p.D18G,CLOCK	1
chr4:56345848	p.S632L,CLOCK	1
chr4:56315585	p.S221Y,CLOCK	1
chr4:56329897	p.S12L,CLOCK	1
chr4:56308687	p.N588N,CLOCK	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 CLOCK 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 CLOCK

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


APOOL,ASXL2,BIRC6,CCNT1,CLOCK,DDI2,DNAJB14, DPP8,EXOC6B,GTF2A1,LCOR,MAP3K2,NBEAL1,RC3H2, REST,RIF1,RSC1A1,SON,STRN,UHMK1,WDFY3	APC,ASXL2,CLOCK,ELK4,HIPK1,HMBOX1,LMBRD2, MAP3K2,MARCH6,MED13,NBEAL1,NHLRC2,RC3H2,RSC1A1, STRN,TAOK1,TRIP12,TTBK2,UBR1,UHMK1,YIPF6

ANKRD17,ANKRD36BP1,ASXL2,CLOCK,DDI2,ETV3,GTF2A1, HEATR5A,HIPK1,HIPK3,LCOR,LUZP1,MAN1A2,MAN2A1, MYO9A,REL,REST,SON,TAOK1,TRIP11,UHMK1	CLOCK,DDI2,DHX33,DPP8,AGO2,FAM63B,HIPK3, IL6ST,KIAA0754,LATS1,LNPEP,MAN1A2,PIK3C2A,PREX2, PTPRG,RAD54L2,RC3H2,RIF1,SHROOM4,TAOK1,TRIM44

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 CLOCK

There's no related Drug.

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Cross referenced IDs for CLOCK

* 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