TISIDB

Summary
Symbol	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
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	PF01590 GAF domain PF00233 3'5'-cyclic nucleotide phosphodiesterase
Function	Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).

> Gene Ontology [ TOP ]
Biological Process	GO:0002683 negative regulation of immune system process GO:0002694 regulation of leukocyte activation GO:0002695 negative regulation of leukocyte activation GO:0003012 muscle system process GO:0003013 circulatory system process GO:0003015 heart process GO:0003300 cardiac muscle hypertrophy GO:0006140 regulation of nucleotide metabolic process GO:0006195 purine nucleotide catabolic process GO:0006936 muscle contraction GO:0006937 regulation of muscle contraction GO:0006941 striated muscle contraction GO:0006942 regulation of striated muscle contraction GO:0007159 leukocyte cell-cell adhesion GO:0007162 negative regulation of cell adhesion GO:0007281 germ cell development GO:0007292 female gamete generation GO:0008015 blood circulation GO:0008016 regulation of heart contraction GO:0009150 purine ribonucleotide metabolic process GO:0009154 purine ribonucleotide catabolic process GO:0009166 nucleotide catabolic process GO:0009187 cyclic nucleotide metabolic process GO:0009214 cyclic nucleotide catabolic process GO:0009261 ribonucleotide catabolic process GO:0009994 oocyte differentiation GO:0010611 regulation of cardiac muscle hypertrophy GO:0010613 positive regulation of cardiac muscle hypertrophy GO:0010720 positive regulation of cell development GO:0014742 positive regulation of muscle hypertrophy GO:0014743 regulation of muscle hypertrophy GO:0014896 muscle hypertrophy GO:0014897 striated muscle hypertrophy GO:0019439 aromatic compound catabolic process GO:0022407 regulation of cell-cell adhesion GO:0022408 negative regulation of cell-cell adhesion GO:0022412 cellular process involved in reproduction in multicellular organism GO:0030799 regulation of cyclic nucleotide metabolic process GO:0030823 regulation of cGMP metabolic process GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032945 negative regulation of mononuclear cell proliferation GO:0033674 positive regulation of kinase activity GO:0034655 nucleobase-containing compound catabolic process GO:0042098 T cell proliferation GO:0042110 T cell activation GO:0042129 regulation of T cell proliferation GO:0042130 negative regulation of T cell proliferation GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043500 muscle adaptation GO:0043502 regulation of muscle adaptation GO:0043900 regulation of multi-organism process GO:0043902 positive regulation of multi-organism process GO:0044057 regulation of system process GO:0044270 cellular nitrogen compound catabolic process GO:0045822 negative regulation of heart contraction GO:0045860 positive regulation of protein kinase activity GO:0045932 negative regulation of muscle contraction GO:0045988 negative regulation of striated muscle contraction GO:0046068 cGMP metabolic process GO:0046069 cGMP catabolic process GO:0046434 organophosphate catabolic process GO:0046651 lymphocyte proliferation GO:0046700 heterocycle catabolic process GO:0048477 oogenesis GO:0048599 oocyte development GO:0050670 regulation of lymphocyte proliferation GO:0050672 negative regulation of lymphocyte proliferation GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050866 negative regulation of cell activation GO:0050868 negative regulation of T cell activation GO:0051249 regulation of lymphocyte activation GO:0051250 negative regulation of lymphocyte activation GO:0055117 regulation of cardiac muscle contraction GO:0055118 negative regulation of cardiac muscle contraction GO:0055119 relaxation of cardiac muscle GO:0060047 heart contraction GO:0060048 cardiac muscle contraction GO:0060281 regulation of oocyte development GO:0060282 positive regulation of oocyte development GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070664 negative regulation of leukocyte proliferation GO:0071593 lymphocyte aggregation GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0072523 purine-containing compound catabolic process GO:0090075 relaxation of muscle GO:0090257 regulation of muscle system process GO:1900542 regulation of purine nucleotide metabolic process GO:1901136 carbohydrate derivative catabolic process GO:1901292 nucleoside phosphate catabolic process GO:1901361 organic cyclic compound catabolic process GO:1901565 organonitrogen compound catabolic process GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903038 negative regulation of leukocyte cell-cell adhesion GO:1903522 regulation of blood circulation GO:1903523 negative regulation of blood circulation GO:2000241 regulation of reproductive process GO:2000243 positive regulation of reproductive process
Molecular Function	GO:0004112 cyclic-nucleotide phosphodiesterase activity GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity GO:0008081 phosphoric diester hydrolase activity GO:0019001 guanyl nucleotide binding GO:0030551 cyclic nucleotide binding GO:0030553 cGMP binding GO:0032561 guanyl ribonucleotide binding GO:0042578 phosphoric ester hydrolase activity GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04022 cGMP-PKG signaling pathway hsa00230 Purine metabolism
Reactome	R-HSA-109582: Hemostasis R-HSA-392154: Nitric oxide stimulates guanylate cyclase R-HSA-418346: Platelet homeostasis R-HSA-418457: cGMP effects

Summary
Symbol	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PDE5A 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 ]

Literatures describing the relation between PDE5A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25564570	Head and Neck Squamous Cell Carcinoma	Inhibit immunity (T cell function)	This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor-specific immune suppression in patients with head and neck cancer, with potential for therapeutic application.
25320361	Head and Neck Squamous Cell Carcinoma	Inhibit immunity (T cell function)	PDE5 inhibitor tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma.
24878583	myeloma	Promote immunity	Here, we show how the addition of the PDE5 inhibitor, tadalafil, in a patient with end-stage relapsed/refractory multiple myeloma reduced MDSC function and generated a dramatic and durable antimyeloma immune and clinical response.

Summary
Symbol	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
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

[ TOP ]

Statistical results of PDE5A 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	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
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

[ TOP ]

Points in the above scatter plot represent the expression difference of PDE5A 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	-0.363	0.203
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.774	0.181
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.059	0.896
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.238	0.632
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.382	0.863
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.056	0.984
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.17	0.656
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.56	0.641
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.214	0.866
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.36	0.689
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	1.532	0.169
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.278	0.048

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of PDE5A 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	1
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	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PDE5A. 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	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PDE5A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PDE5A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PDE5A. 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	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PDE5A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PDE5A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PDE5A
Name	phosphodiesterase 5A, cGMP-specific
Aliases	CGB-PDE; CN5A; PDE5; cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase; cGMP-specific pho ......
Chromosomal Location	4q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PDE5A collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting PDE5A.

ID	Name	Drug Type	Targets	#Targets
DB00201	Caffeine	Small Molecule	ADORA1, ADORA2A, ATM, ITPR1, ITPR2, ITPR3, PDE10A, PDE11A, PDE1A, ......	33
DB00203	Sildenafil	Small Molecule	PDE5A, PDE6G, PDE6H	3
DB00277	Theophylline	Small Molecule	ADORA1, ADORA2A, ADORA2B, CPNE1, HDAC2, HM13, NOMO1, PARP1, PDE3A, ......	14
DB00806	Pentoxifylline	Small Molecule	ADORA1, ADORA2A, NT5E, PDE4A, PDE4B, PDE5A	6
DB00820	Tadalafil	Small Molecule	PDE11A, PDE5A	2
DB00862	Vardenafil	Small Molecule	PDE5A, PDE6G, PDE6H	3
DB00975	Dipyridamole	Small Molecule	ADA, ORM1, PDE10A, PDE4A, PDE5A, RCAN1	6
DB01972	Guanosine-5'-Monophosphate	Small Molecule	ATIC, DLG4, GMPR, GUK1, HINT1, PDE5A, TGM3	7
DB03597	Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine	Small Molecule	GSTM4, PDE5A, PDE9A	3
DB04272	Citric Acid	Small Molecule	AKR1B1, ANG, APRT, BHMT, C8G, CPB1, CS, CTDSP1, GNMT, HGS, HS3ST3A ......	23
DB05415	OSI-461	Small Molecule	PDE5A	1
DB06237	Avanafil	Small Molecule	PDE5A	1
DB06246	Exisulind	Small Molecule	AKR1B1, AKR1B10, GSTP1, PDE2A, PDE4C, PDE4D, PDE5A	7
DB06267	Udenafil	Small Molecule	PDE5A	1
DB07954	3-isobutyl-1-methyl-7H-xanthine	Small Molecule	PDE2A, PDE3B, PDE4D, PDE5A, PDE6G, PDE7A, PDE8A, PDE9A	8
DB08729	5-ethoxy-4-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-2-sulfonamide	Small Molecule	PDE5A	1
DB09283	Trapidil	Small Molecule	PDE10A, PDE11A, PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE3B, PDE4A, P ......	21

Browse PDE5A