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 SDHD

Basic gene info.	Gene symbol	SDHD
	Gene name	succinate dehydrogenase complex, subunit D, integral membrane protein
	Synonyms	CBT1\|CII-4\|CWS3\|PGL\|PGL1\|QPs3\|SDH4\|cybS
	Cytomap	UCSC genome browser: 11q23
	Genomic location	chr11 :111957570-111966518
	Type of gene	protein-coding
	RefGenes	NM_001276503.1, NM_001276504.1,NM_001276506.1,NM_003002.3,NR_077060.1,
	Ensembl id	ENSG00000204370
	Description	succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrialsuccinate-ubiquinone oxidoreductase cytochrome b small subunitsuccinate-ubiquinone reductase membrane anchor subunit
	Modification date	20141219
dbXrefs	MIM : 602690
	HGNC : HGNC
	Ensembl : ENSG00000204370
	HPRD : 04069
	Vega : OTTHUMG00000166997
Protein	UniProt: O14521 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_SDHD
	BioGPS: 6392
	Gene Expression Atlas: ENSG00000204370
	The Human Protein Atlas: ENSG00000204370
Pathway	NCI Pathway Interaction Database: SDHD
	KEGG: SDHD
	REACTOME: SDHD
	ConsensusPathDB
	Pathway Commons: SDHD
Metabolism	MetaCyc: SDHD
	HUMANCyc: SDHD
Regulation	Ensembl's Regulation: ENSG00000204370
	miRBase: chr11 :111,957,570-111,966,518
	TargetScan: NM_001276503
	cisRED: ENSG00000204370
Context	iHOP: SDHD
	cancer metabolism search in PubMed: SDHD
	UCL Cancer Institute: SDHD
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of SDHD in cancer cell metabolism	1. Baysal BE (2003) On the association of succinate dehydrogenase mutations with hereditary paraganglioma. Trends in Endocrinology & Metabolism 14: 453-459. go to article 2. Puissegur M, Mazure N, Bertero T, Pradelli L, Grosso S, et al. (2011) miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death & Differentiation 18: 465-478. go to article

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

Cancer Description
Cancer	CGAP: SDHD
	Familial Cancer Database: SDHD

* 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_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE

Others
OMIM	114900; phenotype. 168000; phenotype. 171300; phenotype. 602690; gene. 606864; phenotype. 615106; phenotype.
Orphanet	100093; Carcinoid tumor and carcinoid syndrome. 201; Cowden syndrome. 29072; Hereditary pheochromocytoma-paraganglioma. 3208; Isolated succinate-CoQ reductase deficiency. 97286; Carney-Stratakis syndrome.
Disease	KEGG Disease: SDHD
	MedGen: SDHD (Human Medical Genetics with Condition)
	ClinVar: SDHD
Phenotype	MGI: SDHD (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: SDHD

Mutations for SDHD

* 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
prostate	SDHD	chr11	111963712	111963712		chr11	115734775	115734775

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 SDHD 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

AA213804

SDHD

198

111965577

111965774

XIRP2

199

309

168106959

168107074

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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=13)	Stat. for Synonymous SNVs (# total SNVs=5)

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
chr11:111958593-111958593	p.R22Q	3
chr11:111959687-111959687	p.S89C	1
chr11:111958619-111958619	p.I31V	1
chr11:111959712-111959712	p.A97A	1
chr11:111958662-111958662	p.G45E	1
chr11:111965564-111965564	p.G117V	1
chr11:111958687-111958687	p.P53P	1
chr11:111965573-111965573	p.L120S	1
chr11:111958696-111958696	p.H56H	1
chr11:111965589-111965589	p.K125N	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	2	1		4					1			3					1		1	4
# mutation	2	1		4					1			3					1		1	4
nonsynonymous SNV				4					1			2							1	3
synonymous SNV	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
chr11:111958593	p.R22Q,SDHD	2
chr11:111965564	p.E30K,SDHD	1
chr11:111958687	p.V33V,SDHD	1
chr11:111965680	p.L37F,SDHD	1
chr11:111958696	p.L37H,SDHD	1
chr11:111965691	p.L38L,SDHD	1
chr11:111959621	p.S50C,SDHD	1
chr11:111959626	p.A58A,SDHD	1
chr11:111959637	p.G69W,SDHD	1
chr11:111959647	p.L117M,SDHD	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 SDHD 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 SDHD

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


ALG9,ARCN1,ATP5L,C11orf57,CWF19L2,DDX10,DLAT, EI24,NPAT,PTS,PUS3,RBM7,REXO2,RPS25, SDHD,STT3A,TMEM123,UBE4A,USP28,ZPR1,ZW10	ACAT1,ATPAF1,MPC1,DLD,GHITM,GNPAT,GPN3, HADHB,MRPS36,NDUFB5,PDHX,PHYH,PPP3CB,PRDX3, RRAGD,SDHB,SDHD,SNRNP27,SUCLA2,VBP1,VDAC2

ATP5F1,ATP5G3,ATP5L,ATP5O,C14orf142,COX7A2,MRPL21, MRPL35,MRPS22,NDUFB5,NDUFS3,SAR1B,SDHB,SDHD, SUCLG1,TIMM8B,TMEM126A,TMEM126B,TMX2,TOMM22,UQCRC2	ATG5,ATP5C1,ATP5F1,ATP5O,TMEM251,C14orf142,C3orf38, COX7A2,FAM96A,HINT1,MRPL13,MRPS36,NDUFB5,NXT2, ORC4,PDZD11,PPCS,SDHB,SDHD,TXNL1,UQCRC2

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 SDHD

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Organism-specific databases	PharmGKB	PA35608; -.
Organism-specific databases	CTD	6392; -.

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
DB00139	succinate dehydrogenase complex, subunit D, integral membrane protein	approved; nutraceutical	Succinic acid
DB00756	succinate dehydrogenase complex, subunit D, integral membrane protein	approved	Hexachlorophene
DB04141	succinate dehydrogenase complex, subunit D, integral membrane protein	experimental	2-Hexyloxy-6-Hydroxymethyl-Tetrahydro-Pyran-3,4,5-Triol
DB08689	succinate dehydrogenase complex, subunit D, integral membrane protein	experimental	UBIQUINONE-1

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Cross referenced IDs for SDHD

* 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