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 PHGDH

Basic gene info.	Gene symbol	PHGDH
	Gene name	phosphoglycerate dehydrogenase
	Synonyms	3-PGDH\|3PGDH\|HEL-S-113\|NLS\|NLS1\|PDG\|PGAD\|PGD\|PGDH\|PHGDHD\|SERA
	Cytomap	UCSC genome browser: 1p12
	Genomic location	chr1 :120254418-120286849
	Type of gene	protein-coding
	RefGenes	NM_006623.3,
	Ensembl id	ENSG00000092621
	Description	3-phosphoglycerate dehydrogenaseD-3-phosphoglycerate dehydrogenaseepididymis secretory protein Li 113
	Modification date	20141211
dbXrefs	MIM : 606879
	HGNC : HGNC
	Ensembl : ENSG00000092621
	HPRD : 06047
	Vega : OTTHUMG00000012100
Protein	UniProt: O43175 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PHGDH
	BioGPS: 26227
	Gene Expression Atlas: ENSG00000092621
	The Human Protein Atlas: ENSG00000092621
Pathway	NCI Pathway Interaction Database: PHGDH
	KEGG: PHGDH
	REACTOME: PHGDH
	ConsensusPathDB
	Pathway Commons: PHGDH
Metabolism	MetaCyc: PHGDH
	HUMANCyc: PHGDH
Regulation	Ensembl's Regulation: ENSG00000092621
	miRBase: chr1 :120,254,418-120,286,849
	TargetScan: NM_006623
	cisRED: ENSG00000092621
Context	iHOP: PHGDH
	cancer metabolism search in PubMed: PHGDH
	UCL Cancer Institute: PHGDH
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of PHGDH in cancer cell metabolism	1. Mullarky E, Mattaini KR, Vander Heiden MG, Cantley LC, Locasale JW (2011) PHGDH amplification and altered glucose metabolism in human melanoma. Pigment cell & melanoma research 24: 1112-1115. go to article 2. Kim HM, Jung WH, Koo JS (2014) Site-specific metabolic phenotypes in metastatic breast cancer. Journal of translational medicine 12: 1-17. go to article 3. Mattaini KR, Brignole EJ, Kini M, Davidson SM, Fiske BP, et al. (2015) An epitope tag alters phosphoglycerate dehydrogenase structure and impairs ability to support cell proliferation. Cancer Metab 3: 5. doi: 10.1186/s40170-015-0131-7. pmid: 4414297. go to article 4. Ou Y, Wang SJ, Jiang L, Zheng B, Gu W (2015) p53 Protein-mediated regulation of phosphoglycerate dehydrogenase (PHGDH) is crucial for the apoptotic response upon serine starvation. J Biol Chem 290: 457-466. doi: 10.1074/jbc.M114.616359. pmid: 4281747. go to article 5. Kim SK, Jung WH, Koo JS (2014) Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. PLoS One 9: e101004. doi: 10.1371/journal.pone.0101004. pmid: 4076239. go to article 6. Chen J, Chung F, Yang G, Pu M, Gao H, et al. (2013) Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth. Oncotarget 4: 2502-2511. pmid: 3926844. go to article 7. Ma L, Tao Y, Duran A, Llado V, Galvez A, et al. (2013) Control of nutrient stress-induced metabolic reprogramming by PKCzeta in tumorigenesis. Cell 152: 599-611. doi: 10.1016/j.cell.2012.12.028. pmid: 3963830. go to article

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

Cancer Description
Cancer	CGAP: PHGDH
	Familial Cancer Database: PHGDH

* 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_GLYCINE_SERINE_AND_THREONINE_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM	256520; phenotype. 601815; phenotype. 606879; gene.
Orphanet	2671; Neu-Laxova syndrome. 79351; 3-phosphoglycerate dehydrogenase deficiency.
Disease	KEGG Disease: PHGDH
	MedGen: PHGDH (Human Medical Genetics with Condition)
	ClinVar: PHGDH
Phenotype	MGI: PHGDH (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: PHGDH

Mutations for PHGDH

* 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 PHGDH 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
BF804555	PHGDH	11	147	1	120284422	120285464	PHGDH	137	214	1	120285552	120285630
BE844016	HLA-DRA	15	189	6	3759098	3759271	PHGDH	184	239	1	120286659	120286714
AW261826	PHGDH	19	400	1	120285616	120286838	EPHX1	395	553	1	226016559	226019583
BC004528	PHGDH	49	889	1	120254576	120278045	UBAC2	887	2734	13	99896770	100038682

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=4

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=35)	Stat. for Synonymous SNVs (# total SNVs=12)

Stat. for Deletions (# total SNVs=1)	Stat. for Insertions (# total SNVs=0)
	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
chr1:120263849-120263849	p.N65N	4
chr1:120284428-120284428	p.A373T	3
chr1:120285546-120285546	p.T442T	3
chr1:120279735-120279735	p.?	2
chr1:120277917-120277917	p.?	2
chr1:120269623-120269623	p.?	2
chr1:120263923-120263923	p.R90K	2
chr1:120254648-120254648	p.M1I	2
chr1:120279853-120279853	p.F303F	2
chr1:120283043-120283043	p.P327L	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	1			5	1				2			8	2	1			4	2	1	11
# mutation	1			5	1				2			8	2	1			4	2	1	11
nonsynonymous SNV				3	1				2			6	2				2	2	1	5
synonymous SNV	1			2								2		1			2			6

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
chr1:120279853	p.F303F	2
chr1:120284439	p.R119M	1
chr1:120263907	p.R294H	1
chr1:120277939	p.P122P	1
chr1:120284452	p.C295Y	1
chr1:120263915	p.A124V	1
chr1:120277957	p.R135Q	1
chr1:120284473	p.V376V	1
chr1:120266064	p.R163Q	1
chr1:120277960	p.E381Q	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 PHGDH 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 PHGDH

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


AMBN,ATP1A1,BPI,CMC2,CNTN6,FRZB,FTMT, KCNJ16,MDGA2,NCALD,NECAB2,NOTCH2,PHGDH,PLSCR5, ROPN1B,SEC22B,SLC39A12,SLC43A3,SPON1,WARS2,ZNF697	ACAD9,FAHD2A,HOOK2,HYI,KLHL22,LPHN1,LRP5, MDFI,MESP1,PHGDH,PPP1R1B,SCRN2,SELENBP1,SF3B2, SLC19A1,SLC25A10,SLC25A6,THRA,TYSND1,VPS26B,WIPI2

AARS,ASNS,ATF4,CARS,CBS,GARS,GPT2, MARS,MTHFD2,PHGDH,PSAT1,SARS,SHMT2,SLC3A2, SLC4A5,SLC7A5,STC2,TARS,ULBP1,XPOT,YARS	ABCC9,ACTA2,ANXA6,AOC3,ATP1A2,CLIP3,CNGA3, CPXM2,FBXL22,FHL3,HRASLS5,LOXL4,MAGEE1,NIPAL4, NLGN1,NPTXR,PDE2A,PHGDH,SLIT2,TGFB1I1,TMEM200B

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 PHGDH

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	ChEMBL	CHEMBL2311243; -.
Organism-specific databases	PharmGKB	PA33264; -.
Organism-specific databases	CTD	26227; -.

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
DB00157	phosphoglycerate dehydrogenase	approved; nutraceutical	NADH
DB01907	phosphoglycerate dehydrogenase	experimental	Nicotinamide-Adenine-Dinucleotide
DB01694	phosphoglycerate dehydrogenase	experimental	D-tartaric acid

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Cross referenced IDs for PHGDH

* 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