TISIDB

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Mitochondrion matrix.
Domain	PF00285 Citrate synthase
Function	-

> Gene Ontology [ TOP ]
Biological Process	GO:0006091 generation of precursor metabolites and energy GO:0006099 tricarboxylic acid cycle GO:0006101 citrate metabolic process GO:0009060 aerobic respiration GO:0015980 energy derivation by oxidation of organic compounds GO:0045333 cellular respiration GO:0072350 tricarboxylic acid metabolic process
Molecular Function	GO:0004108 citrate (Si)-synthase activity GO:0016746 transferase activity, transferring acyl groups GO:0036440 citrate synthase activity GO:0046912 transferase activity, transferring acyl groups, acyl groups converted into alkyl on transfer
Cellular Component	GO:0005759 mitochondrial matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00020 Citrate cycle (TCA cycle) hsa00630 Glyoxylate and dicarboxylate metabolism hsa01100 Metabolic pathways hsa01200 Carbon metabolism hsa01210 2-Oxocarboxylic acid metabolism hsa01230 Biosynthesis of amino acids
Reactome	R-HSA-71403: Citric acid cycle (TCA cycle) R-HSA-1430728: Metabolism R-HSA-392499: Metabolism of proteins R-HSA-1268020: Mitochondrial protein import R-HSA-71406: Pyruvate metabolism and Citric Acid (TCA) cycle R-HSA-1428517: The citric acid (TCA) cycle and respiratory electron transport

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CS and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CS in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	logFC: 1.20; FDR: 0.001060	Sensitive to T cell-mediated killing
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CS in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.112	0.572
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.058	0.983
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.152	0.939
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.336	0.316
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.105	0.961
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.63	0.817
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.003	0.994
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.039	0.985
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.006	0.998
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.358	0.854
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.717	0.809
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.011	0.844

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CS in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	11.1	0	11.1	0.0181
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	0	11.1	0.0286
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CS. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CS. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CS. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CS. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CS expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CS and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CS
Name	citrate synthase
Aliases	citrate (Si)-synthase; Citrate synthase, mitochondrial
Chromosomal Location	12q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CS collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CS.

ID	Name	Drug Type	Targets	#Targets
DB01969	Trifluoroacetonyl Coenzyme A	Small Molecule	CS	1
DB01992	Coenzyme A	Small Molecule	ACAT2, CRAT, CS, DBI, HMGCR, KAT2A, KAT2B, KAT5	8
DB02637	Oxaloacetate Ion	Small Molecule	CS, SPR	2
DB03182	Alpha-Fluoro-Carboxymethyldethia Coenzyme a Complex	Small Molecule	CS	1
DB03499	Malate Ion	Small Molecule	CS, ME2	2
DB04230	Nitromethyldethia Coenzyme A	Small Molecule	CS	1
DB04272	Citric Acid	Small Molecule	AKR1B1, ANG, APRT, BHMT, C8G, CPB1, CS, CTDSP1, GNMT, HGS, HS3ST3A ......	23

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