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 FPGS

Basic gene info.	Gene symbol	FPGS
	Gene name	folylpolyglutamate synthase
	Synonyms	-
	Cytomap	UCSC genome browser: 9q34.1
	Genomic location	chr9 :130565507-130576556
	Type of gene	protein-coding
	RefGenes	NM_001018078.2, NM_001288803.1,NM_004957.5,NR_110170.1,
	Ensembl id	ENSG00000136877
	Description	folylpoly-gamma-glutamate synthetasefolylpolyglutamate synthase, mitochondrialtetrahydrofolate synthasetetrahydrofolylpolyglutamate synthase
	Modification date	20141207
dbXrefs	MIM : 136510
	HGNC : HGNC
	Ensembl : ENSG00000136877
	HPRD : 00642
	Vega : OTTHUMG00000020716
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_FPGS
	BioGPS: 2356
	Gene Expression Atlas: ENSG00000136877
	The Human Protein Atlas: ENSG00000136877
Pathway	NCI Pathway Interaction Database: FPGS
	KEGG: FPGS
	REACTOME: FPGS
	ConsensusPathDB
	Pathway Commons: FPGS
Metabolism	MetaCyc: FPGS
	HUMANCyc: FPGS
Regulation	Ensembl's Regulation: ENSG00000136877
	miRBase: chr9 :130,565,507-130,576,556
	TargetScan: NM_001018078
	cisRED: ENSG00000136877
Context	iHOP: FPGS
	cancer metabolism search in PubMed: FPGS
	UCL Cancer Institute: FPGS
Assigned class in ccmGDB	C

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

Cancer Description
Cancer	CGAP: FPGS
	Familial Cancer Database: FPGS

* 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

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

Mutations for FPGS

* 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	FPGS	chr9	130569321	130569341	SH2D3C	chr9	130537332	130537352

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 FPGS 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
BE514681	COBL	213	244	7	51336581	51336612	FPGS	242	481	9	130572003	130573276
CN275141	FPGS	51	150	9	130565894	130565993	FPGS	145	581	9	130565673	130566264
BF772512	FPGS	5	103	9	130569942	130570585	FPGS	100	270	9	130566642	130566979

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=40)	Stat. for Synonymous SNVs (# total SNVs=9)

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
chr9:130565267-130565267	p.I22V	4
chr9:130566821-130566821	p.T104M	3
chr9:130575672-130575672	p.S518I	2
chr9:130566572-130566572	p.V49V	2
chr9:130575758-130575758	p.H547D	2
chr9:130569923-130569923	p.D234N	2
chr9:130569293-130569293	p.N143S	2
chr9:130566616-130566616	p.Q64R	1
chr9:130570869-130570869	p.A285A	1
chr9:130575553-130575553	p.D478E	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=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	1	1		5			3	1	3			1	2	1			2	2		6
# mutation	1	1		5			3	1	3			1	2	1			2	2		6
nonsynonymous SNV	1	1		3			1	1	3			1	2	1			2	1		5
synonymous SNV				2			2											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
chr9:130569923	p.D208N,FPGS	2
chr9:130569337	p.R108H,FPGS	1
chr9:130570890	p.A425T,FPGS	1
chr9:130569338	p.L113M,FPGS	1
chr9:130570896	p.N449K,FPGS	1
chr9:130569352	p.P125S,FPGS	1
chr9:130571113	p.G469S,FPGS	1
chr9:130569509	p.T132A,FPGS	1
chr9:130572339	p.S471S,FPGS	1
chr9:130569530	p.G178D,FPGS	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 FPGS 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 FPGS

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


AK1,C9orf114,CDK9,COQ4,DPM2,EDF1,ENDOG, FBXW5,FPGS,LRSAM1,NTMT1,NUDT22,PHPT1,PPP2R4, PTGES2,PTRH1,SLC2A8,SSNA1,TOR2A,UCK1,URM1	BSG,C20orf27,EIF4EBP1,ETFB,F8A1,FPGS,GCDH, GCHFR,MAPK11,MPST,PCYT2,PMM1,POLR2E,PQLC1, PSMA7,SLC25A10,SLC25A1,SLC2A4RG,SNX8,TMEM120A,TSPO

ARPC5L,C9orf142,CDK9,NELFB,COQ4,EDF1,ENDOG, FPGS,NTMT1,MRPL41,PMPCA,PPP2R4,PTGES2,PTRH1, SH3GLB2,SSNA1,TOR2A,TUBB4B,UBAC1,WDR34,ZDHHC12	C19orf10,DHRS13,FARSA,FPGS,HMBS,METTL1,MRPL4, MTX1,NUDT8,NUP85,PDF,PMM2,PPIB,PUSL1, PYCR1,PYCRL,RRP9,RUVBL2,ALYREF,THOC6,TSFM

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 FPGS

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
DB00142	folylpolyglutamate synthase	approved; nutraceutical	L-Glutamic Acid
DB00293	folylpolyglutamate synthase	approved; investigational	Raltitrexed
DB00544	folylpolyglutamate synthase	approved	Fluorouracil
DB00650	folylpolyglutamate synthase	approved	Leucovorin
DB00145	folylpolyglutamate synthase	approved; nutraceutical	Glycine
DB00133	folylpolyglutamate synthase	approved; nutraceutical	L-Serine
DB00515	folylpolyglutamate synthase	approved	Cisplatin
DB00252	folylpolyglutamate synthase	approved	Phenytoin
DB00563	folylpolyglutamate synthase	approved	Methotrexate
DB00642	folylpolyglutamate synthase	approved; investigational	Pemetrexed

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Cross referenced IDs for FPGS

* 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