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 FASN

Basic gene info.	Gene symbol	FASN
	Gene name	fatty acid synthase
	Synonyms	FAS\|OA-519\|SDR27X1
	Cytomap	UCSC genome browser: 17q25
	Genomic location	chr17 :80036213-80056106
	Type of gene	protein-coding
	RefGenes	NM_004104.4,
	Ensembl id	ENSG00000169710
	Description	short chain dehydrogenase/reductase family 27X, member 1
	Modification date	20141207
dbXrefs	MIM : 600212
	HGNC : HGNC
	Ensembl : ENSG00000169710
	HPRD : 02567
	Vega : OTTHUMG00000178527
Protein	UniProt: P49327 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_FASN
	BioGPS: 2194
	Gene Expression Atlas: ENSG00000169710
	The Human Protein Atlas: ENSG00000169710
Pathway	NCI Pathway Interaction Database: FASN
	KEGG: FASN
	REACTOME: FASN
	ConsensusPathDB
	Pathway Commons: FASN
Metabolism	MetaCyc: FASN
	HUMANCyc: FASN
Regulation	Ensembl's Regulation: ENSG00000169710
	miRBase: chr17 :80,036,213-80,056,106
	TargetScan: NM_004104
	cisRED: ENSG00000169710
Context	iHOP: FASN
	cancer metabolism search in PubMed: FASN
	UCL Cancer Institute: FASN
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of FASN in cancer cell metabolism	1. Chang L, Wu P, Senthilkumar R, Tian X, Liu H, et al. (2015) Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway. J Cancer Res Clin Oncol. doi: 10.1007/s00432-015-2000-8. go to article 2. Patel AV, Johansson G, Colbert MC, Dasgupta B, Ratner N (2015) Fatty acid synthase is a metabolic oncogene targetable in malignant peripheral nerve sheath tumors. Neuro Oncol. doi: 10.1093/neuonc/nov076. go to article 3. Benjamin DI, Li DS, Lowe W, Heuer T, Kemble G, et al. (2015) Diacylglycerol Metabolism and Signaling Is a Driving Force Underlying FASN Inhibitor Sensitivity in Cancer Cells. ACS Chem Biol 10: 1616-1623. doi: 10.1021/acschembio.5b00240. go to article 4. Lee YJ, Choi HS, Seo MJ, Jeon HJ, Kim KJ, et al. (2015) Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish. Food Funct. doi: 10.1039/c5fo00481k. go to article 5. Loubiere C, Goiran T, Laurent K, Djabari Z, Tanti JF, et al. (2015) Metformin-induced energy deficiency leads to the inhibition of lipogenesis in prostate cancer cells. Oncotarget 6: 15652-15661. go to article

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

Cancer Description
Cancer	CGAP: FASN
	Familial Cancer Database: FASN

* 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_VITAMINS_AND_COFACTORS REACTOME_INTEGRATION_OF_ENERGY_METABOLISM REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	600212; gene. 600212; gene.
Orphanet
Disease	KEGG Disease: FASN
	MedGen: FASN (Human Medical Genetics with Condition)
	ClinVar: FASN
Phenotype	MGI: FASN (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: FASN

Mutations for FASN

* 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

There's no intra-chromosomal structural variation.

Sample

Symbol_a

Chr_a

Start_a

End_a

Symbol_b

Chr_b

Start_b

End_b

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 FASN 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
BG982750	C19orf6	5	290	19	1011617	1012147	FASN	280	416	17	80046844	80046980
BE818191	FASN	16	164	17	80050813	80051160	LAMB1	155	309	7	107601021	107601731
BM710952	HTT	5	177	4	3243627	3243805	FASN	161	287	17	80036843	80036969
AF155114	FBXO9	1	1719	6	52930247	52962684	FASN	1715	2716	17	80036214	80037572
AF172068	FASN	1	352	17	80046335	80046976	ESR1	341	1218	6	152265458	152420101
AI970549	LOC100507424	3	73	12	2966846	2966916	FASN	71	749	17	80040912	80042485
AF172069	FASN	1	352	17	80046335	80046976	ESR1	341	1218	6	152265458	152420101
BE818234	FASN	4	152	17	80050813	80051160	LAMB1	143	297	7	107601021	107601731
BG982743	C19orf6	31	310	19	1011625	1012147	FASN	300	436	17	80046844	80046980

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=4

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=121)	Stat. for Synonymous SNVs (# total SNVs=66)

Stat. for Deletions (# total SNVs=6)	Stat. for Insertions (# total SNVs=2)

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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
chr17:80040808-80040808	p.R1917C	4
chr17:80040450-80040450	p.E1958K	2
chr17:80051183-80051183	p.N189N	2
chr17:80037290-80037290	p.R2447R	2
chr17:80053328-80053328	p.R50W	2
chr17:80042406-80042406	p.S1584F	2
chr17:80051640-80051640	p.N96N	2
chr17:80045211-80045211	p.D1071E	2
chr17:80041293-80041293	p.I1784V	2
chr17:80049354-80049354	p.A413fs*39	2

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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=2

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	8	2	17	1		6		4	4		12	7	1	1	1	17	15	1	14
# mutation	2	8	2	18	1		7		4	4		12	7	1	1	1	21	18	1	22
nonsynonymous SNV	2	5	2	14			4		3	3		10	2	1	1	1	12	10	1	11
synonymous SNV		3		4	1		3		1	1		2	5				9	8		11

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
chr17:80046702	p.M785I	2
chr17:80049217	p.A458V	2
chr17:80045689	p.P972L	2
chr17:80049304	p.R429H	2
chr17:80039054	p.R80R	1
chr17:80042140	p.L1760S	1
chr17:80045871	p.S1427F	1
chr17:80049317	p.K1072K	1
chr17:80040272	p.A810T	1
chr17:80043235	p.P2267P	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 FASN 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 FASN

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.

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Protein Expression Plot (RPPA)

*RPPA protein expression data were extracted from TCPA (The Cancer Proteome Atlas). Normalized data based on replicated based normalization (RBN) was used to draw following figures.

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


ACACA,ALDH4A1,ALOX15B,CCDC57,DCXR,ELOVL5,ETNK2, FASN,FKBP5,GGT1,GGTLC1,GNMT,MPV17L,MVK, SCD,SERHL2,SLC26A3,SLC26A6,SREBF1,ZBTB16,ZNF689	ACSM2A,ALDH1L1,C17orf53,IZUMO4,C20orf27,APMAP,CKB, CYB5A,FASN,FGFRL1,GCDH,GLUL,LDHD,NDRG4, PC,PCYT2,PMM1,SHMT1,SLC25A10,SLC25A1,TM7SF2

ACACA,ACLY,CAD,DDB1,DHCR7,DHX37,EIF4G1, FASN,GCN1L1,HNRNPM,HTT,INCENP,KIAA0100,KPNB1, LSS,PCNXL3,PCSK9,PDCD11,POLR1A,SCD,SOCS7	ACACA,ACSL1,ALPL,CAD,DHCR7,AGO2,FASN, LARP1,LSS,MUC4,MUC5B,PKP4,PLXNA1,POLR1A, PRKDC,RANGAP1,SCD,SPTBN2,TNKS1BP1,URB1,USP31

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 FASN

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P49327; -.
Chemistry	ChEMBL	CHEMBL4158; -.
Chemistry	BindingDB	P49327; -.
Chemistry	ChEMBL	CHEMBL4158; -.
Organism-specific databases	PharmGKB	PA28006; -.
Organism-specific databases	PharmGKB	PA28006; -.
Organism-specific databases	CTD	2194; -.
Organism-specific databases	CTD	2194; -.

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
DB01034	fatty acid synthase	approved	Cerulenin
DB01083	fatty acid synthase	approved; investigational	Orlistat
DB00363	fatty acid synthase	approved	Clozapine
DB00502	fatty acid synthase	approved	Haloperidol

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Cross referenced IDs for FASN

* 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