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 ACACA

Basic gene info.	Gene symbol	ACACA
	Gene name	acetyl-CoA carboxylase alpha
	Synonyms	ACAC\|ACACAD\|ACC\|ACC1\|ACCA
	Cytomap	UCSC genome browser: 17q21
	Genomic location	chr17 :35441926-35766902
	Type of gene	protein-coding
	RefGenes	NM_198834.2, NM_198836.2,NM_198837.1,NM_198838.1,NM_198839.2, NM_000664.3,NM_198835.1,
	Ensembl id	ENSG00000132142
	Description	ACC-alphaacetyl-CoA carboxylase 1acetyl-Coenzyme A carboxylase alpha
	Modification date	20141207
dbXrefs	MIM : 200350
	HGNC : HGNC
	Ensembl : ENSG00000278540
	HPRD : 01938
	Vega : OTTHUMG00000188463
Protein	UniProt: Q13085 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ACACA
	BioGPS: 31
	Gene Expression Atlas: ENSG00000132142
	The Human Protein Atlas: ENSG00000132142
Pathway	NCI Pathway Interaction Database: ACACA
	KEGG: ACACA
	REACTOME: ACACA
	ConsensusPathDB
	Pathway Commons: ACACA
Metabolism	MetaCyc: ACACA
	HUMANCyc: ACACA
Regulation	Ensembl's Regulation: ENSG00000132142
	miRBase: chr17 :35,441,926-35,766,902
	TargetScan: NM_198834
	cisRED: ENSG00000132142
Context	iHOP: ACACA
	cancer metabolism search in PubMed: ACACA
	UCL Cancer Institute: ACACA
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of ACACA in cancer cell metabolism	1. Moreno-Navarrete JM, Moreno M, Vidal M, Ortega F, Serrano M, et al. (2015) Deleted in breast cancer 1 plays a functional role in adipocyte differentiation. Am J Physiol Endocrinol Metab 308: E554-561. doi: 10.1152/ajpendo.00286.2014. go to article 2. Volden PA, Wonder EL, Skor MN, Carmean CM, Patel FN, et al. (2013) Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. Cancer Prev Res (Phila) 6: 634-645. doi: 10.1158/1940-6207.CAPR-12-0458. pmid: 3881320 go to article 3. Corominas-Faja B, Cuyas E, Gumuzio J, Bosch-Barrera J, Leis O, et al. (2014) Chemical inhibition of acetyl-CoA carboxylase suppresses self-renewal growth of cancer stem cells. Oncotarget 5: 8306-8316. pmid: 4226684 go to article 4. Leyssens C, Marien E, Verlinden L, Derua R, Waelkens E, et al. (2015) Remodeling of phospholipid composition in colon cancer cells by 1alpha,25(OH)2D3 and its analogs. J Steroid Biochem Mol Biol 148: 172-178. doi: 10.1016/j.jsbmb.2015.01.018. go to article 5. Vazquez-Martin A, Corominas-Faja B, Cufi S, Vellon L, Oliveras-Ferraros C, et al. (2013) The mitochondrial H(+)-ATP synthase and the lipogenic switch: new core components of metabolic reprogramming in induced pluripotent stem (iPS) cells. Cell Cycle 12: 207-218. doi: 10.4161/cc.23352. pmid: 3575450 go to article

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

Cancer Description
Cancer	CGAP: ACACA
	Familial Cancer Database: ACACA

* 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_PYRUVATE_METABOLISM KEGG_PROPANOATE_METABOLISM REACTOME_INTEGRATION_OF_ENERGY_METABOLISM REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS

Others
OMIM	200350; gene. 200350; gene. 613933; phenotype. 613933; phenotype.
Orphanet
Disease	KEGG Disease: ACACA
	MedGen: ACACA (Human Medical Genetics with Condition)
	ClinVar: ACACA
Phenotype	MGI: ACACA (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: ACACA

Mutations for ACACA

* 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

* Inter-chromosomal variantions includes 'interchromosomal amplicon to amplicon', 'interchromosomal amplicon to non-amplified dna', 'interchromosomal insertion', 'Interchromosomal unknown type'.

- 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
central_nervous_system	ACACA	chr17	35755632	35755632	ACACA	chr17	35758826	35758826
central_nervous_system	ACACA	chr17	35755643	35755643	ACACA	chr17	35758807	35758807
ovary	ACACA	chr17	35492008	35492028	ACACA	chr17	35492271	35492291
ovary	ACACA	chr17	35507739	35507759	GGNBP2	chr17	34914207	34914227
ovary	ACACA	chr17	35512781	35512801	AATF	chr17	35406977	35406997
ovary	ACACA	chr17	35530905	35530925	ACACA	chr17	35534243	35534263
ovary	ACACA	chr17	35532393	35532413		chr17	45046026	45046046
ovary	ACACA	chr17	35657517	35657537	ADRBK2	chr22	26008739	26008759
ovary	ACACA	chr17	35714732	35714752		chr17	45039058	45039078
pancreas	ACACA	chr17	35453740	35453760	MRPL45	chr17	36461866	36461886
pancreas	ACACA	chr17	35476890	35476910	ACACA	chr17	35478795	35478815
pancreas	ACACA	chr17	35499723	35499743	ACACA	chr17	35617114	35617134
pancreas	ACACA	chr17	35628366	35628386	ACACA	chr17	35631005	35631025
pancreas	ACACA	chr17	35654318	35654338	STK3	chr8	99698169	99698189
pancreas	ACACA	chr17	35741875	35741895	LOC440434	chr17	36401752	36401772
pancreas	ACACA	chr17	35752230	35752250	ACACA	chr17	35758781	35758801
pancreas	ACACA	chr17	35755483	35755683	ACACA	chr17	35758697	35758897

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 ACACA 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
BF910869	RGPD5	1	143	2	113146685	113146827	ACACA	137	191	17	35591930	35591984
XX000005	ACACA	1	71	17	35479453	35479523	STAC2	70	150	17	37374348	37374428
BF511511	DOK3	25	368	5	176928911	176929254	ACACA	362	439	17	35540059	35540136
BF800878	ACACA	15	169	17	35765424	35765578	PRKDC	162	285	8	48798797	48798920

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	ns	ovary	pancre	prost	skin	stoma	thyro	urina
Total # sample	12			3			4		1		1				4		2
GAIN (# sample)	11			2			4		1		1				4		2
LOSS (# sample)	2			1													1

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=5

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=176)	Stat. for Synonymous SNVs (# total SNVs=44)

Stat. for Deletions (# total SNVs=3)	Stat. for Insertions (# total SNVs=1)

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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
chr17:35518873-35518873	p.R1629Q	4
chr17:35518742-35518742	p.R1673C	4
chr17:35591977-35591977	p.E958D	2
chr17:35578665-35578665	p.L1126L	2
chr17:35627678-35627678	p.V266V	2
chr17:35518824-35518824	p.S1645S	2
chr17:35506823-35506823	p.H1787Y	2
chr17:35640208-35640208	p.F95F	2
chr17:35486393-35486393	p.P1853S	2
chr17:35627697-35627697	p.G260E	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=4

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	34	5		12		7			16	7	1		1	25	18	1	23
# mutation	14	4	1	36	5		12		7			20	7	1		1	29	22	1	34
nonsynonymous SNV	10	3	1	27	4		11		6			14	4			1	18	16	1	29
synonymous SNV	4	1		9	1		1		1			6	3	1			11	6		5

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
chr17:35518742	p.R1673C,ACACA	4
chr17:35518873	p.R1629Q,ACACA	3
chr17:35468504	p.R918Q,ACACA	2
chr17:35640208	p.L2117L,ACACA	2
chr17:35545329	p.R1460H,ACACA	2
chr17:35506883	p.R2081L,ACACA	2
chr17:35641791	p.F95F,ACACA	2
chr17:35631165	p.E958D,ACACA	2
chr17:35597475	p.G1801R,ACACA	2
chr17:35454849	p.A45V,ACACA	2

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 ACACA 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 ACACA

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.

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Protein Expression Plot (RPPA)

*RPPA protein expression data were extracted from TCPA (The Cancer Proteome Atlas). Normalized data based on replicated based normalization (RBN) was used to draw following figures.

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


ACACA,ACLY,ALCAM,APOOL,AR,ATP7A,CLOCK, CPD,DDX52,FASN,HTT,IDE,KLHL11,LMBRD2, NF1,PRKAR2A,PXMP4,SCD,STT3B,SYNRG,TADA2A	AACS,ACACA,BCKDHB,CSPG5,EYS,FADS1,FADS2, FASN,HIBCH,IDH1,LONP2,LSS,MCCC1,ME1, PNPLA3,SC5D,SCD,SCP2,SUOX,TBC1D24,TMEM132B

AATF,ACACA,C17orf96,CCNE1,CDK12,CWC25,DDX52, FASN,FXYD2,KCNA10,MED1,MED24,MLLT6,MRPL45, PIP4K2B,RGSL1,RPL19,SNAR-A2,SOCS7,STARD3,SYNRG	ACACA,ATXN2,PRRC2A,BAZ1B,CDK5RAP2,CKAP5,DAG1, HERC1,HUWE1,ILF3,IPO9,MDC1,PBRM1,POLR1A, PRKDC,TCHP,TCOF1,TP53BP1,TTLL5,UBAP2L,URB1

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 ACACA

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	Q13085; -.
Chemistry	ChEMBL	CHEMBL3351; -.
Chemistry	GuidetoPHARMACOLOGY	1263; -.
Chemistry	BindingDB	Q13085; -.
Chemistry	ChEMBL	CHEMBL3351; -.
Chemistry	GuidetoPHARMACOLOGY	1263; -.
Organism-specific databases	PharmGKB	PA24421; -.
Organism-specific databases	PharmGKB	PA24421; -.
Organism-specific databases	CTD	31; -.
Organism-specific databases	CTD	31; -.

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
DB00121	acetyl-CoA carboxylase alpha	approved; nutraceutical	Biotin
DB01132	acetyl-CoA carboxylase alpha	approved; investigational	Pioglitazone

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Cross referenced IDs for ACACA

* 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