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 SHMT1

Basic gene info.	Gene symbol	SHMT1
	Gene name	serine hydroxymethyltransferase 1 (soluble)
	Synonyms	CSHMT\|SHMT
	Cytomap	UCSC genome browser: 17p11.2
	Genomic location	chr17 :18231186-18266856
	Type of gene	protein-coding
	RefGenes	NM_001281786.1, NM_004169.4,NM_148918.2,
	Ensembl id	ENSG00000176974
	Description	cytoplasmic serine hydroxymethyltransferaseglycine hydroxymethyltransferaseserine hydroxymethyltransferase, cytosolicserine methylase
	Modification date	20141222
dbXrefs	MIM : 182144
	HGNC : HGNC
	Ensembl : ENSG00000176974
	HPRD : 01643
	Vega : OTTHUMG00000059094
Protein	UniProt: P34896 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_SHMT1
	BioGPS: 6470
	Gene Expression Atlas: ENSG00000176974
	The Human Protein Atlas: ENSG00000176974
Pathway	NCI Pathway Interaction Database: SHMT1
	KEGG: SHMT1
	REACTOME: SHMT1
	ConsensusPathDB
	Pathway Commons: SHMT1
Metabolism	MetaCyc: SHMT1
	HUMANCyc: SHMT1
Regulation	Ensembl's Regulation: ENSG00000176974
	miRBase: chr17 :18,231,186-18,266,856
	TargetScan: NM_001281786
	cisRED: ENSG00000176974
Context	iHOP: SHMT1
	cancer metabolism search in PubMed: SHMT1
	UCL Cancer Institute: SHMT1
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of SHMT1 in cancer cell metabolism	1. MacFarlane AJ, Perry CA, McEntee MF, Lin DM, Stover PJ (2011) Shmt1 heterozygosity impairs folate-dependent thymidylate synthesis capacity and modifies risk of Apcmin-mediated intestinal cancer risk. Cancer research 71: 2098-2107. go to article 2. Paone A, Marani M, Fiascarelli A, Rinaldo S, Giardina G, et al. (2014) SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation. Cell death & disease 5: e1525. go to article

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Phenotypic Information for SHMT1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: SHMT1
	Familial Cancer Database: SHMT1

* 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_VITAMINS_AND_COFACTORS REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM	182144; gene.
Orphanet
Disease	KEGG Disease: SHMT1
	MedGen: SHMT1 (Human Medical Genetics with Condition)
	ClinVar: SHMT1
Phenotype	MGI: SHMT1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: SHMT1

Mutations for SHMT1

* 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 SHMT1 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
BF356130	TFCP2L1	45	321	2	122041465	122041739	SHMT1	309	382	17	18238384	18238457
AX747021	SHMT1	1	2757	17	18233997	18236753	MLLT11	2753	3088	1	151040932	151041267
BF356132	TFCP2L1	9	323	2	122041420	122041739	SHMT1	311	384	17	18238384	18238457
AK091498	SHMT1	1	2757	17	18233997	18236753	MLLT11	2753	3088	1	151040932	151041267

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=27)	Stat. for Synonymous SNVs (# total SNVs=9)

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
chr17:18259194-18259194	p.?	2
chr17:18243507-18243507	p.G222R	2
chr17:18232096-18232096	p.L474F	2
chr17:18232688-18232688	p.L396V	2
chr17:18250892-18250892	p.G146V	2
chr17:18250897-18250897	p.P144P	2
chr17:18257053-18257053	p.R59*	1
chr17:18232648-18232648	p.T409M	1
chr17:18238957-18238957	p.E283*	1
chr17:18250920-18250920	p.R137C	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	1	4			2		1			3	2	2			2	3	1	5
# mutation	1	1	1	4			2		1			3	2	2			2	3	1	5
nonsynonymous SNV	1		1	2			1		1			2		2			1	2		4
synonymous SNV		1		2			1					1	2				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
chr17:18250892	p.G8E,SHMT1	2
chr17:18232688	p.L258V,SHMT1	2
chr17:18233876	p.I221I,SHMT1	1
chr17:18250891	p.L153L,SHMT1	1
chr17:18233878	p.S152F,SHMT1	1
chr17:18233940	p.N149S,SHMT1	1
chr17:18250897	p.F337V,SHMT1	1
chr17:18232093	p.A74V,SHMT1	1
chr17:18233941	p.A321A,SHMT1	1
chr17:18250933	p.R69L,SHMT1	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 SHMT1 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 SHMT1

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


ALKBH5,ATPAF2,B9D1,GID4,COPS3,DRG2,DVL2, EVPLL,FLII,LLGL1,MAPK7,MED9,OR5M3,PIGL, PRPSAP2,SFXN2,SHMT1,MIEF2,SMYD4,TOP3A,ZSWIM7	ACACB,ALDH1L1,ASS1,C17orf53,C20orf27,CIDEA,CKB, CYB5A,ECHDC3,GLUL,HADH,HRSP12,MLXIPL,MOCS1, ORMDL3,PC,SHMT1,SLC25A1,STAT5A,TM7SF2,TMEM120A

ATPAF2,AURKB,C1QBP,COPS3,COX10,ECHS1,EIF4A1, EIF5A,EIF5AL1,ELAC2,FAM64A,GLOD4,MPDU1,PFN1, RNMTL1,SCO1,SHMT1,SLC25A11,TTC19,WRAP53,YWHAE	AKR1A1,DNPH1,C9orf41,CA9,CDCA3,DDC,DHRS4L2, EPHA1,ESPL1,FAH,FANCC,GCHFR,LCLAT1,MOCOS, NPY6R,OTC,PCYT2,PNPO,SHMT1,SLC25A15,SLC2A9

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 SHMT1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P34896; -.
Chemistry	ChEMBL	CHEMBL1772927; -.
Organism-specific databases	PharmGKB	PA35753; -.
Organism-specific databases	CTD	6470; -.

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
DB00114	serine hydroxymethyltransferase 1 (soluble)	nutraceutical	Pyridoxal Phosphate
DB00116	serine hydroxymethyltransferase 1 (soluble)	approved; nutraceutical	Tetrahydrofolic acid
DB00145	serine hydroxymethyltransferase 1 (soluble)	approved; nutraceutical	Glycine
DB01055	serine hydroxymethyltransferase 1 (soluble)	approved	Mimosine
DB02067	serine hydroxymethyltransferase 1 (soluble)	experimental	Triglu-5-Formyl-Tetrahydrofolate
DB02800	serine hydroxymethyltransferase 1 (soluble)	experimental	5-Hydroxymethylene-6-Hydrofolic Acid
DB02824	serine hydroxymethyltransferase 1 (soluble)	experimental	N-Pyridoxyl-Glycine-5-Monophosphate
DB00515	serine hydroxymethyltransferase 1 (soluble)	approved	Cisplatin
DB00531	serine hydroxymethyltransferase 1 (soluble)	approved; investigational	Cyclophosphamide
DB00970	serine hydroxymethyltransferase 1 (soluble)	approved	Dactinomycin
DB00997	serine hydroxymethyltransferase 1 (soluble)	approved; investigational	Doxorubicin
DB00541	serine hydroxymethyltransferase 1 (soluble)	approved; investigational	Vincristine
DB00133	serine hydroxymethyltransferase 1 (soluble)	approved; nutraceutical	L-Serine
DB00563	serine hydroxymethyltransferase 1 (soluble)	approved	Methotrexate
DB00115	serine hydroxymethyltransferase 1 (soluble)	approved; nutraceutical	Cyanocobalamin
DB00158	serine hydroxymethyltransferase 1 (soluble)	approved; nutraceutical	Folic Acid

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Cross referenced IDs for SHMT1

* 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