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 LDHA

Basic gene info.	Gene symbol	LDHA
	Gene name	lactate dehydrogenase A
	Synonyms	GSD11\|HEL-S-133P\|LDH1\|LDHM
	Cytomap	UCSC genome browser: 11p15.4
	Genomic location	chr11 :18415935-18429765
	Type of gene	protein-coding
	RefGenes	NM_001135239.1, NM_001165414.1,NM_001165415.1,NM_001165416.1,NM_005566.3, NR_028500.1,
	Ensembl id	ENSG00000134333
	Description	L-lactate dehydrogenase A chainLDH muscle subunitLDH-ALDH-Mcell proliferation-inducing gene 19 proteinepididymis secretory sperm binding protein Li 133Plactate dehydrogenase Mproliferation-inducing gene 19renal carcinoma antigen NY-REN-59
	Modification date	20141222
dbXrefs	MIM : 150000
	HGNC : HGNC
	Ensembl : ENSG00000134333
	HPRD : 01025
	Vega : OTTHUMG00000167721
Protein	UniProt: P00338 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_LDHA
	BioGPS: 3939
	Gene Expression Atlas: ENSG00000134333
	The Human Protein Atlas: ENSG00000134333
Pathway	NCI Pathway Interaction Database: LDHA
	KEGG: LDHA
	REACTOME: LDHA
	ConsensusPathDB
	Pathway Commons: LDHA
Metabolism	MetaCyc: LDHA
	HUMANCyc: LDHA
Regulation	Ensembl's Regulation: ENSG00000134333
	miRBase: chr11 :18,415,935-18,429,765
	TargetScan: NM_001135239
	cisRED: ENSG00000134333
Context	iHOP: LDHA
	cancer metabolism search in PubMed: LDHA
	UCL Cancer Institute: LDHA
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of LDHA in cancer cell metabolism	1. Dai Q, Yin Q, Wei L, Zhou Y, Qiao C, et al. (2015) Oroxylin A regulates glucose metabolism in response to hypoxic stress with the involvement of Hypoxia-inducible factor-1 in human hepatoma HepG2 cells. Mol Carcinog. doi: 10.1002/mc.22369. go to article 2. Intlekofer AM, Dematteo RG, Venneti S, Finley LW, Lu C, et al. (2015) Hypoxia Induces Production of L-2-Hydroxyglutarate. Cell Metab 22: 304-311. doi: 10.1016/j.cmet.2015.06.023. pmid: 4527873. go to article 3. Ooi AT, Gomperts BN (2015) Molecular Pathways: Targeting Cellular Energy Metabolism in Cancer via Inhibition of SLC2A1 and LDHA. Clin Cancer Res 21: 2440-2444. doi: 10.1158/1078-0432.CCR-14-1209. pmid: 4452440. go to article 4. Maiso P, Huynh D, Moschetta M, Sacco A, Aljawai Y, et al. (2015) Metabolic signature identifies novel targets for drug resistance in multiple myeloma. Cancer Res 75: 2071-2082. doi: 10.1158/0008-5472.CAN-14-3400. pmid: 4433568. go to article

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

Cancer Description
Cancer	CGAP: LDHA
	Familial Cancer Database: LDHA

* 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_CYSTEINE_AND_METHIONINE_METABOLISM KEGG_PYRUVATE_METABOLISM KEGG_PROPANOATE_METABOLISM REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE REACTOME_PYRUVATE_METABOLISM

Others
OMIM	150000; gene. 150000; gene. 612933; phenotype. 612933; phenotype.
Orphanet	284426; Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency. 284426; Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.
Disease	KEGG Disease: LDHA
	MedGen: LDHA (Human Medical Genetics with Condition)
	ClinVar: LDHA
Phenotype	MGI: LDHA (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: LDHA

Mutations for LDHA

* 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 LDHA 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
BM044090	LDHA	1	64	11	18427043	18427106	WIPI2	65	875	7	5262235	5270683
BG179712	LDHA	1	150	11	18429031	18429180	MEST	143	802	7	130145346	130146013
BQ928549	LDHA	1	62	11	18427045	18427106	WIPI2	63	848	7	5262235	5270662
CA424367	BOLA2	19	570	16	29821934	29822485	LDHA	571	654	11	18424385	18424469
BM049309	LDHA	1	64	11	18427043	18427106	WIPI2	65	782	7	5262235	5270603
CA414218	LDHA	18	339	11	18429072	18429394	EIF4EBP2	338	632	10	72163813	72181544
BG775162	LDHA	1	64	11	18427043	18427106	WIPI2	65	794	7	5262235	5270616
BC025288	SKI	1	443	1	2238670	2239112	LDHA	436	2093	11	18416115	18429394
BG122659	PRPF8	1	183	17	1579226	1579560	LDHA	178	765	11	18428658	18429243
BC051361	SKI	1	443	1	2238670	2239112	LDHA	436	2093	11	18416115	18429394
BF893167	GORASP2	1	147	2	171806733	171807914	LDHA	139	460	11	18416110	18421075
CB143668	LDHA	1	158	11	18425250	18427044	ATP5G3	150	434	2	176043940	176046436
BC072009	SKI	1	443	1	2238670	2239112	LDHA	436	2093	11	18416115	18429394

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=6

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=38)	Stat. for Synonymous SNVs (# total SNVs=10)

Stat. for Deletions (# total SNVs=2)	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
chr11:18425274-18425274	p.V209A	6
chr11:18424398-18424398	p.T144A	3
chr11:18421003-18421003	p.V51G	2
chr11:18421014-18421014	p.E55K	2
chr11:18424527-18424527	p.G187W	2
chr11:18418496-18418496	p.A36V	2
chr11:18421071-18421071	p.T74S	1
chr11:18428760-18428760	p.E311K	1
chr11:18424451-18424451	p.S161S	1
chr11:18425304-18425304	p.G219E	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=7

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				13	4		1		1			6		1			4	2	2	6
# mutation				7	5		1		1			6		1			4	2	2	8
nonsynonymous SNV				5	3		1					5		1			4	2	2	7
synonymous SNV				2	2				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
chr11:18425274	p.V151A,LDHA	7
chr11:18421014	p.T86A,LDHA	2
chr11:18421031	p.E55K,LDHA	2
chr11:18424398	p.G60G,LDHA	2
chr11:18424399	p.L72F,LDHA	1
chr11:18427054	p.L196L,LDHA	1
chr11:18424404	p.G80V,LDHA	1
chr11:18428671	p.A199T,LDHA	1
chr11:18421030	p.R135C,LDHA	1
chr11:18424451	p.Y223C,LDHA	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 LDHA 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 LDHA

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


AFAP1L1,ARHGAP31,EOGT,AGPAT4-IT1,CAV2,CCDC82,CLIC4, CPNE8,EHBP1,FAM126A,FERMT2,FNDC3B,LATS2,LDHAL6B, LOC400927,MAML2,MYO1E,PLEKHG1,QKI,RBMS1,TMEM43	ABHD13,ABL2,AHR,TMEM263,CTTNBP2NL,FAM91A1,GNAI3, GNB4,HIAT1,KRAS,LDHAL6B,MAPK1IP1L,NCOA7,PAQR3, PIGA,RIPK2,SERPINB8,SGMS2,SLC25A32,ZNF207,ZBTB21

AKAP13,ARL14,ELMSAN1,MIR22HG,DENND3,DOCK5,EHBP1L1, FRMD4B,JOSD1,KDM6B,LDHAL6B,MNT,MXD1,MYO1E, NBEAL1,NEAT1,PTPRH,RREB1,TET2,TLN2,ZZEF1	AKAP8,BCL3,CFAP45,DGCR11,EPHA2,GADD45A,HRH1, LDHAL6B,LDLR,MAP2K3,MCL1,NRG1,NABP1,SENP2, SKIL,SLC25A44,SLC25A45,TRIM51,TCTE1,TNFRSF12A,ZNF800

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 LDHA

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P00338; -.
Chemistry	ChEMBL	CHEMBL4835; -.
Chemistry	BindingDB	P00338; -.
Chemistry	ChEMBL	CHEMBL4835; -.
Organism-specific databases	PharmGKB	PA30319; -.
Organism-specific databases	PharmGKB	PA30319; -.
Organism-specific databases	CTD	3939; -.
Organism-specific databases	CTD	3939; -.

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	lactate dehydrogenase A	approved; nutraceutical	NADH
DB01907	lactate dehydrogenase A	experimental	Nicotinamide-Adenine-Dinucleotide
DB02483	lactate dehydrogenase A	experimental	Etheno-Nad
DB02701	lactate dehydrogenase A	experimental	Nicotinamide
DB03940	lactate dehydrogenase A	experimental	Oxamic Acid
DB00171	lactate dehydrogenase A	approved; nutraceutical	Adenosine triphosphate
DB00119	lactate dehydrogenase A	approved; nutraceutical	Pyruvic acid

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Cross referenced IDs for LDHA

* 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