TISIDB

Summary
Symbol	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
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	-
Domain	PF00383 Cytidine and deoxycytidylate deaminase zinc-binding region
Function	This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.

> Gene Ontology [ TOP ]
Biological Process	GO:0001558 regulation of cell growth GO:0006140 regulation of nucleotide metabolic process GO:0006206 pyrimidine nucleobase metabolic process GO:0006213 pyrimidine nucleoside metabolic process GO:0006216 cytidine catabolic process GO:0008655 pyrimidine-containing compound salvage GO:0009112 nucleobase metabolic process GO:0009116 nucleoside metabolic process GO:0009119 ribonucleoside metabolic process GO:0009163 nucleoside biosynthetic process GO:0009164 nucleoside catabolic process GO:0009972 cytidine deamination GO:0016049 cell growth GO:0019439 aromatic compound catabolic process GO:0019858 cytosine metabolic process GO:0030308 negative regulation of cell growth GO:0034655 nucleobase-containing compound catabolic process GO:0042454 ribonucleoside catabolic process GO:0043094 cellular metabolic compound salvage GO:0043097 pyrimidine nucleoside salvage GO:0043174 nucleoside salvage GO:0044270 cellular nitrogen compound catabolic process GO:0045926 negative regulation of growth GO:0045980 negative regulation of nucleotide metabolic process GO:0046087 cytidine metabolic process GO:0046131 pyrimidine ribonucleoside metabolic process GO:0046133 pyrimidine ribonucleoside catabolic process GO:0046134 pyrimidine nucleoside biosynthetic process GO:0046135 pyrimidine nucleoside catabolic process GO:0046700 heterocycle catabolic process GO:0051259 protein oligomerization GO:0051260 protein homooligomerization GO:0051262 protein tetramerization GO:0051289 protein homotetramerization GO:0072527 pyrimidine-containing compound metabolic process GO:0072528 pyrimidine-containing compound biosynthetic process GO:0072529 pyrimidine-containing compound catabolic process GO:1901136 carbohydrate derivative catabolic process GO:1901361 organic cyclic compound catabolic process GO:1901565 organonitrogen compound catabolic process GO:1901657 glycosyl compound metabolic process GO:1901658 glycosyl compound catabolic process GO:1901659 glycosyl compound biosynthetic process
Molecular Function	GO:0004126 cytidine deaminase activity GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds GO:0016814 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines GO:0019239 deaminase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00240 Pyrimidine metabolism hsa00983 Drug metabolism - other enzymes hsa01100 Metabolic pathways
Reactome	R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-1430728: Metabolism R-HSA-15869: Metabolism of nucleotides R-HSA-6798695: Neutrophil degranulation R-HSA-73848: Pyrimidine metabolism R-HSA-73614: Pyrimidine salvage reactions

Summary
Symbol	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CDA 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

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Literatures describing the relation between CDA and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
20404277	Plasmacytoma	Inhibit immunity; Resistant to immunotherapy	In this study, we report that small interfering RNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by CTLs. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells, and upregulation of CD200 was shown to be in favor of tumor eradication by CTLs.

Summary
Symbol	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
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 CDA 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	NA/NS	NA/NS
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	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
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 CDA 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	0.21	0.648
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.016	0.987
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.384	0.58
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.195	0.721
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.016	0.266
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.849	0.416
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.124	0.834
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.026	0.976
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.324	0.725
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.333	0.168
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	0.729	0.668
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.156	0.438

> Mutation difference between responders and non-responders

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

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	2.7	-2.7	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDA. 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	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDA. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDA. 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	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CDA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CDA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CDA
Name	cytidine deaminase
Aliases	cytosine nucleoside deaminase; small cytidine deaminase
Chromosomal Location	1p36.2-p35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CDA collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CDA.

ID	Name	Drug Type	Targets	#Targets
DB03185	1-Beta-Ribofuranosyl-1,3-Diazepinone	Small Molecule	CDA	1

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