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 SPHK2

Basic gene info.	Gene symbol	SPHK2
	Gene name	sphingosine kinase 2
	Synonyms	SK 2\|SK-2\|SPK 2\|SPK-2
	Cytomap	UCSC genome browser: 19q13.2
	Genomic location	chr19 :49122547-49133663
	Type of gene	protein-coding
	RefGenes	NM_001204158.2, NM_001204159.2,NM_001204160.2,NM_001243876.1,NM_020126.4,
	Ensembl id	ENSG00000063176
	Description	sphingosine kinase type 2
	Modification date	20141207
dbXrefs	MIM : 607092
	HGNC : HGNC
	Ensembl : ENSG00000063176
	HPRD : 06157
	Vega : OTTHUMG00000183318
Protein	UniProt: Q9NRA0 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_SPHK2
	BioGPS: 56848
	Gene Expression Atlas: ENSG00000063176
	The Human Protein Atlas: ENSG00000063176
Pathway	NCI Pathway Interaction Database: SPHK2
	KEGG: SPHK2
	REACTOME: SPHK2
	ConsensusPathDB
	Pathway Commons: SPHK2
Metabolism	MetaCyc: SPHK2
	HUMANCyc: SPHK2
Regulation	Ensembl's Regulation: ENSG00000063176
	miRBase: chr19 :49,122,547-49,133,663
	TargetScan: NM_001204158
	cisRED: ENSG00000063176
Context	iHOP: SPHK2
	cancer metabolism search in PubMed: SPHK2
	UCL Cancer Institute: SPHK2
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of SPHK2 in cancer cell metabolism	1. Engel N, Lisec J, Piechulla B, Nebe B (2012) Metabolic profiling reveals sphingosine-1-phosphate kinase 2 and lyase as key targets of (phyto-) estrogen action in the breast cancer cell line mcf-7 and not in mcf-12a. go to article 2. Degagné E, Saba JD (2014) S1pping fire: Sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer. Clinical and experimental gastroenterology 7: 205. go to article

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Phenotypic Information for SPHK2(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: SPHK2
	Familial Cancer Database: SPHK2

* 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_SPHINGOLIPID_METABOLISM KEGG_FC_GAMMA_R_MEDIATED_PHAGOCYTOSIS REACTOME_PHOSPHOLIPID_METABOLISM REACTOME_SPHINGOLIPID_METABOLISM REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	607092; gene.
Orphanet
Disease	KEGG Disease: SPHK2
	MedGen: SPHK2 (Human Medical Genetics with Condition)
	ClinVar: SPHK2
Phenotype	MGI: SPHK2 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: SPHK2

Mutations for SPHK2

* 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 SPHK2 related fusion information.

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

C02583

MAP1A

166

43814856

43815229

SPHK2

163

317

49133508

49133661

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=42)	Stat. for Synonymous SNVs (# total SNVs=18)

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
chr19:49132881-49132881	p.R606C	3
chr19:49132634-49132634	p.L523L	3
chr19:49129486-49129486	p.G126G	3
chr19:49131042-49131042	p.N202S	2
chr19:49132338-49132338	p.L425F	2
chr19:49132104-49132104	p.S347G	2
chr19:49131491-49131491	p.G277S	2
chr19:49123805-49123805	p.D12N	2
chr19:49132383-49132383	p.P440T	2
chr19:49131947-49131947	p.P294P	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	4	3	1	5	2		2		2			2	2				10	3		5
# mutation	5	3	1	5	2		2		2			2	2				10	3		5
nonsynonymous SNV	3	2		4			1		1			2	1				7	1		3
synonymous SNV	2	1	1	1	2		1		1				1				3	2		2

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
chr19:49132307	p.S378S,SPHK2	2
chr19:49132338	p.L389V,SPHK2	2
chr19:49132082	p.P13S,SPHK2	1
chr19:49132515	p.R274W,SPHK2	1
chr19:49131293	p.P486L,SPHK2	1
chr19:49132111	p.G17G,SPHK2	1
chr19:49129225	p.L280L,SPHK2	1
chr19:49132520	p.S537S,SPHK2	1
chr19:49131440	p.R44H,SPHK2	1
chr19:49132129	p.R292C,SPHK2	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 SPHK2 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 SPHK2

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


ARMC5,BBC3,TMEM259,CAPN10,CCDC9,CROCC,CYTH2, FLYWCH1,GLTSCR1,IRF2BP1,MIB2,MZF1,PNKP,PPP1R12C, RHOT2,SNRNP70,SPHK2,SPSB3,TBC1D17,ZNF205,ZNF628	AAMP,ARFRP1,BRF1,ST20-AS1,BRAT1,NELFB,FAM73B, GTF2H4,HDGFRP2,HGS,PEX16,PFKL,PNKP,SCAF1, SELO,SIX5,SPHK2,SPSB3,TAF6L,TELO2,WDR83

B3GNT8,CYP2B6,DHX34,ENGASE,EPN1,FBXO46,GLTSCR1, HNF1A,NAPA,NR1I2,PPP2R1A,PRR12,SCAF1,SGK2, SLC39A5,SPHK2,SYMPK,VIL1,ZBTB45,ZNF526,ZNF787	ACADS,ACSF3,BAIAP2L2,CEBPA,DAPK2,DHRS11,DOLPP1, ESPN,FAM73B,HECTD3,LPCAT3,MAP2K2,MGAT4B,PLEKHG6, PPAP2C,PPP1R16A,RAB40C,SPHK2,SPINT1,ULK3,ZBTB7B

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 SPHK2

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	Q9NRA0; -.
Chemistry	ChEMBL	CHEMBL3023; -.
Chemistry	GuidetoPHARMACOLOGY	2205; -.
Organism-specific databases	PharmGKB	PA38719; -.
Organism-specific databases	CTD	56848; -.

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
DB00143	sphingosine kinase 2	approved; nutraceutical	Glutathione

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Cross referenced IDs for SPHK2

* 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