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 GPI

Basic gene info.	Gene symbol	GPI
	Gene name	glucose-6-phosphate isomerase
	Synonyms	AMF\|GNPI\|NLK\|PGI\|PHI\|SA-36\|SA36
	Cytomap	UCSC genome browser: 19q13.1
	Genomic location	chr19 :34856031-34893318
	Type of gene	protein-coding
	RefGenes	NM_000175.3, NM_001184722.1,NM_001289789.1,NM_001289790.1,
	Ensembl id	ENSG00000105220
	Description	autocrine motility factorglucose phosphate isomerasehexose monophosphate isomerasehexosephosphate isomeraseneuroleukinoxoisomerasephosphoglucose isomerasephosphohexomutasephosphohexose isomerasephosphosaccharomutasesperm antigen 36sperm antigen
	Modification date	20141207
dbXrefs	MIM : 172400
	HGNC : HGNC
	Ensembl : ENSG00000105220
	HPRD : 01394
	Vega : OTTHUMG00000182087
Protein	UniProt: P06744 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_GPI
	BioGPS: 2821
	Gene Expression Atlas: ENSG00000105220
	The Human Protein Atlas: ENSG00000105220
Pathway	NCI Pathway Interaction Database: GPI
	KEGG: GPI
	REACTOME: GPI
	ConsensusPathDB
	Pathway Commons: GPI
Metabolism	MetaCyc: GPI
	HUMANCyc: GPI
Regulation	Ensembl's Regulation: ENSG00000105220
	miRBase: chr19 :34,856,031-34,893,318
	TargetScan: NM_000175
	cisRED: ENSG00000105220
Context	iHOP: GPI
	cancer metabolism search in PubMed: GPI
	UCL Cancer Institute: GPI
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of GPI in cancer cell metabolism	1. Niinaka Y, Harada K, Fujimuro M, Oda M, Haga A, et al. (2010) Silencing of autocrine motility factor induces mesenchymal-to-epithelial transition and suppression of osteosarcoma pulmonary metastasis. Cancer Res 70: 9483-9493. doi: 10.1158/0008-5472.CAN-09-3880. pmid: 2982894. go to article 2. Lin LL, Hsia CR, Hsu CL, Huang HC, Juan HF (2015) Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells. BMC Genomics 16: 41. doi: 10.1186/s12864-015-1230-0. pmid: 4328042. go to article 3. Zou W, Al-Rubeai M (2015) Understanding central carbon metabolism of rapidly proliferating mammalian cells based on analysis of key enzymatic activities in GS-CHO cell lines. Biotechnol Appl Biochem. doi: 10.1002/bab.1409. go to article 4. Kim HR, Roe JS, Lee JE, Cho EJ, Youn HD (2013) p53 regulates glucose metabolism by miR-34a. Biochem Biophys Res Commun 437: 225-231. doi: 10.1016/j.bbrc.2013.06.043. go to article

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

Cancer Description
Cancer	CGAP: GPI
	Familial Cancer Database: GPI

* 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
KEGG_GLYCOLYSIS_GLUCONEOGENESIS KEGG_STARCH_AND_SUCROSE_METABOLISM KEGG_AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR_METABOLISM BIOCARTA_GLYCOLYSIS_PATHWAY REACTOME_METABOLISM_OF_CARBOHYDRATES REACTOME_GLUCOSE_METABOLISM

Others
OMIM	172400; gene. 613470; phenotype.
Orphanet	712; Hemolytic anemia due to glucophosphate isomerase deficiency.
Disease	KEGG Disease: GPI
	MedGen: GPI (Human Medical Genetics with Condition)
	ClinVar: GPI
Phenotype	MGI: GPI (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: GPI

Mutations for GPI

* 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
breast	GPI	chr19	34860391	34860391	GPI	chr19	34873874	34873874
pancreas	GPI	chr19	34893029	34893049		chr19	43253123	43253143

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 GPI 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
AW366833	AGXT2L2	8	100	5	177648021	177648114	GPI	101	163	19	34859538	34859600
AW369844	AGXT2L2	4	104	5	177648014	177648114	GPI	105	167	19	34859538	34859600
CB046420	GPI	24	326	19	34868441	34870455	FDPS	322	436	1	155290342	155290456
DB005136	GPI	1	55	19	34856101	34856155	NFKB2	56	540	10	104154272	104156743
AV703221	GPI	1	212	19	34893033	34893244	STAR	213	411	8	38001350	38001602
BE898941	GPI	1	502	19	34887484	34890958	TM2D1	503	732	1	62147846	62148079
AF187554	GPI	187	2113	19	34856124	34891143	FBN1	2114	2671	15	48712787	48716414
BQ316137	ARL15	165	222	5	53580235	53580292	GPI	217	518	19	34884819	34887504
CB046419	FDPS	35	149	1	155290342	155290456	GPI	145	447	19	34868441	34870455
AI342169	GPI	22	371	19	34892969	34893318	FGF2	362	480	4	123814902	123815020
BF870824	GPI	1	208	19	34875115	34875322	CDC37	203	385	19	10506640	10506822
BP302114	GPI	1	215	19	34856101	34857271	HDAC8	214	458	X	71708790	71715070
BF358813	GPI	6	201	19	34877702	34877899	MYH11	198	478	16	15897730	15898010

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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=41)	Stat. for Synonymous SNVs (# total SNVs=18)

Stat. for Deletions (# total SNVs=1)	Stat. for Insertions (# total SNVs=1)

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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
chr19:34890129-34890129	p.F429F	3
chr19:34856216-34856216	p.Q15Q	2
chr19:34884178-34884178	p.W277*	2
chr19:34887543-34887543	p.R417Q	2
chr19:34859562-34859562	p.M119I	2
chr19:34890861-34890861	p.A533S	2
chr19:34884959-34884959	p.A350A	2
chr19:34868642-34868642	p.G163G	2
chr19:34868649-34868649	p.M166L	1
chr19:34887329-34887329	p.H396Y	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	4	1		11			2		2			7	5	3	1		5	5		6
# mutation	4	1		10			2		2			8	4	3	1		6	5		7
nonsynonymous SNV	2	1		5			2		1			6	4	2			3	5		6
synonymous SNV	2			5					1			2	1	1	1		3			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
chr19:34884959	p.A322A,GPI	2
chr19:34890129	p.G49G,GPI	2
chr19:34857274	p.R245S,GPI	2
chr19:34884165	p.F401L,GPI	2
chr19:34856216	p.Q15Q,GPI	2
chr19:34856261	p.F30F,GPI	1
chr19:34859595	p.K147N,GPI	1
chr19:34868778	p.F471F,GPI	1
chr19:34857254	p.T43A,GPI	1
chr19:34884965	p.T150A,GPI	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 GPI 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 GPI

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


ATP5G3,BOLA3,COX6B1,ENO1,GAPDH,GPI,LSR, MRPS5,PDCD2L,PDCD5,PDHA1,PFKP,PGAM1,PKM, PSMB2,TIMM50,TMEM147,TPI1,TUBA1C,UQCRH,UQCRHL	ACAA2,ACOT1,ACOT2,ACSS2,AKT2,ANXA6,ATP5G3, BTBD6,NATD1,MROH8,CS,DLST,EIF2B3,GPI, HSDL2,ITGA7,PDHA1,PFKFB1,PPP1R1A,RNF157,TESK1

ALDOA,ATP5B,BCAT2,CS,EIF3K,ENO1,FBL, GAPDH,GPI,GYS1,HSPBP1,IMMT,PGAM1,RDH13, RUVBL2,SARS2,SNRPA,TOMM40,TPI1,UBE2S,UQCRFS1	DAZAP1,DDB1,EIF3B,ELAVL1,FOXM1,GANAB,GPI, HNRNPM,KHSRP,LMNB2,LONP1,MED24,MTHFD1,NOC2L, RANGAP1,RNF26,TBCD,TBL3,TMEM201,USP5,VARS

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 GPI

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA28841; -.
Organism-specific databases	CTD	2821; -.

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
DB02007	glucose-6-phosphate isomerase	experimental	Alpha-D-Glucose-6-Phosphate
DB02076	glucose-6-phosphate isomerase	experimental	6-Phosphogluconic Acid
DB02093	glucose-6-phosphate isomerase	experimental	5-Phospho-D-Arabinohydroxamic Acid
DB02548	glucose-6-phosphate isomerase	experimental	Sorbitol 6-phosphate
DB03042	glucose-6-phosphate isomerase	experimental	5-Phosphoarabinonic Acid
DB03581	glucose-6-phosphate isomerase	experimental	Glucose-6-Phosphate
DB03937	glucose-6-phosphate isomerase	experimental	Erythose-4-Phosphate
DB04493	glucose-6-phosphate isomerase	experimental	Fructose-6-Phosphate
DB00121	glucose-6-phosphate isomerase	approved; nutraceutical	Biotin

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Cross referenced IDs for GPI

* 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