mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

Gene Summary

Ligand Binding Site Mutation Information

Protein Structure Related Information

Gene Expression and Gene-Gene Network

Phenotype Information

Pharmacological Information

Conservation Information for LBS

Gene summary for PDE5A
Gene summary
Basic gene Info.Gene symbolPDE5A
Gene namephosphodiesterase 5A, cGMP-specific
SynonymsCGB-PDE|CN5A|PDE5
CytomapUCSC genome browser: 4q27
Type of geneprotein-coding
RefGenesNM_001083.3,
NM_033430.2,NM_033437.3,
DescriptioncGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterasecGMP-specific 3',5'-cyclic phosphodiesterasecGMP-specific phosphodiesterase PDE5A2cGMP-specific phosphodiesterase type 5Aphosphodiesterase isozyme 5
Modification date20141207
dbXrefs MIM : 603310
HGNC : HGNC
Ensembl : ENSG00000138735
HPRD : 04497
Vega : OTTHUMG00000132971
ProteinUniProt: O76074
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PDE5A
BioGPS: 8654
PathwayNCI Pathway Interaction Database: PDE5A
KEGG: PDE5A
REACTOME: PDE5A
Pathway Commons: PDE5A
ContextiHOP: PDE5A
ligand binding site mutation search in PubMed: PDE5A
UCL Cancer Institute: PDE5A
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0046069cGMP catabolic process14687666


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Ligand binding site mutations for PDE5A
Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)
 : non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
Y709K710NCOAD1
K730R732QHNSC1
F820I821THNSC1
I778R777QSKCM1
K730R732QSKCM1
F787F787CSTAD1
I778R777WUCEC1
F786F786LUCEC1
cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, 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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Protein structure related information for PDE5A
Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
  (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)
: nsSNV at non-LBS: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.
LBSAAchange of nsSNVRelative stability change
F820I821T-1.4674548
F787F787C-1.1972107
I778R777Q-0.88337121
K730R732Q-0.7248752
Y709K710N-0.65227778
F786F786L-0.62696321
I778R777W-0.57328033
(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for PDE5A from PDB

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Differential gene expression and gene-gene network for PDE5A
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)
* Left PPI network was created from samples with mutations in the LBS of PDE5A and the right PPI network was created from samples without mutations in the LBS of PDE5A. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


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Phenotype information for PDE5A
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0027627Neoplasm Metastasis1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for PDE5A
Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network
Drug information targeting mutLBSgene (Approved drugs only)
Drug statusDrugBank IDNameTypeDrug structure
Approved|investigationalDB00203SildenafilSmall molecule
ApprovedDB00277TheophyllineSmall molecule
Approved|investigationalDB00806PentoxifyllineSmall molecule
Approved|investigationalDB00820TadalafilSmall molecule
ApprovedDB00862VardenafilSmall molecule
ApprovedDB00975DipyridamoleSmall molecule
ExperimentalDB01972Guanosine-5'-MonophosphateSmall molecule
ExperimentalDB03597Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]GlycineSmall molecule
Nutraceutical|vet_approvedDB04272Citric AcidSmall molecule
InvestigationalDB05415OSI-461Small molecule
ApprovedDB06237AvanafilSmall molecule
Approved|investigationalDB06267UdenafilSmall molecule
ExperimentalDB079543-isobutyl-1-methyl-7H-xanthineSmall molecule
ExperimentalDB087295-ethoxy-4-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-2-sulfonamideSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PDE5A go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
CIATADALAFIL1uduAF786 F787 F820
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE1rkpAF786 F820
5GPGMP RESIDUE1t9sBF786 F820
VIASILDENAFIL1tbfAF786 F820
VDNVARDENAFIL1uhoAF786 F820
CIATADALAFIL1xozAF786 F820
VDNVARDENAFIL1xp0AF786 F820
VIASILDENAFIL2h42AF786 F820
VIASILDENAFIL2h42BF786 F820
VIASILDENAFIL2h42CF786 F820
WAN5-ETHOXY-4-(1-METHYL-7-OXO-3-PROPYL-6,7-DIHYDRO-1H-PYRAZOLO[4,3-D]PYRIMIDIN-5-YL)THIOPHENE-2-SULFONAMIDE3bjcAF786 F820
VIASILDENAFIL3jwqBF786 F820
VIASILDENAFIL3jwqCF786 F820
VIASILDENAFIL3jwqDF786 F820
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3jwrAF786 F820
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3jwrBF786 F820
5FO6-ETHYL-5-FLUORO-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2-PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE3shyAF786 F820
5CO5-CHLORO-6-ETHYL-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2-PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE3shzAF786 F820
5BO5-BROMO-6-ETHYL-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2-PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE3sieAF786 F820
0H37-(6-METHOXYPYRIDIN-3-YL)-4-{[2-(PROPAN-2-YLOXY)ETHYL]AMINO}-1-(2-PROPOXYETHYL)PYRIDO[4,3-D]PYRIMIDIN-2(1H)-ONE3tggAF786 F820
5EO6-ETHYL-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2- PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE3tseAF786 F820
5IO6-ETHYL-5-IODO-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]- 2-PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE3tsfAF786 F820
NI05,6-DIETHYL-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2- PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE4g2wAF786 F820
NI52-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2- PROPOXYPHENYL}-3,5,6,7-TETRAHYDRO-4H- CYCLOPENTA[D]PYRIMIDIN-4-ONE4g2yAF786 F820
5BA5-BROMO-2-{5-[(4-METHYLPIPERAZIN-1-YL)ACETYL]-2- PROPOXYPHENYL}-6-(PROPAN-2-YL)PYRIMIDIN-4(3H)-ONE4i9zAF786 F820
5BB5-BROMO-2-{2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL) SULFONYL]PHENYL}-6-OCTYLPYRIMIDIN-4(3H)-ONE4ia0AF786 F820
5IO6-ETHYL-5-IODO-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]- 2-PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE4oewAF786 F820
5EO6-ETHYL-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2- PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE4oexAF786 F820
24E3-(4-HYDROXYBENZYL)-1-(THIOPHEN-2-YL)CHROMENO[2,3- C]PYRROL-9(2H)-ONE4md6AF787 F820
5GPGMP RESIDUE1t9sAF820
VIASILDENAFIL1udtAF820
VDNVARDENAFIL3b2rAF820
VDNVARDENAFIL3b2rBF820
PD46-(6-METHOXYPYRIDIN-3-YL)-2-[(2-MORPHOLIN-4-YLETHYL)AMINO]-4-(2-PROPOXYETHYL)PYRIDO[2,3-B]PYRAZIN-3(4H)-ONE3hc8AF820
PD65-AMINO-1-BUTYL-7-PHENYL-1,6-NAPHTHYRIDIN-4(1H)-ONE3hdzAF820
VIASILDENAFIL3jwqAF820
IIIPeptide ligand (GLU,ALA,PHE,ASN,HIS,LEU,GLU,LEU,HIS,GLU,LEU,ALA,GLN,TYR,GLY,ILE,ILE)3jwrBF820
5BO5-BROMO-6-ETHYL-2-{5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]-2-PROPOXYPHENYL}PYRIMIDIN-4(3H)-ONE3sieBF820
CIATADALAFIL1uduBI778 F786 F787 F820
7CAICARISID II2h44AI778 F786 F820
TGE7-(6-METHOXYPYRIDIN-3-YL)-3-{[2-(MORPHOLIN-4-YL)ETHYL]AMINO}-1-(2-PROPOXYETHYL)PYRIDO[3,4-B]PYRAZIN-2(1H)-ONE3tgeAI778 F786 F820
IIIPeptide ligand (GLU,ALA,PHE,ASN,HIS,LEU,GLU,LEU,HIS,GLU,LEU,ALA,GLN,TYR,GLY,ILE,ILE)3jwrAK730
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3jwrAY709
IBM3-ISOBUTYL-1-METHYL-9H-XANTHINE3jwrBY709


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Conservation information for LBS of PDE5A
Multiple alignments for O76074 in multiple species
LBSAA sequence# speciesSpecies
A726LATDLALYIKR5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
A767ACDLSAITKPW5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
A779IQQRIAELVAT3Homo sapiens, Bos taurus, Canis lupus familiaris
A779IQQRIAELVAA2Mus musculus, Rattus norvegicus
A783IAELVATEFFD3Homo sapiens, Bos taurus, Canis lupus familiaris
A783IAELVAAEFFD2Mus musculus, Rattus norvegicus
A823VGFIDAICLQL5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
C677LAQLYCHSIME4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
C677LAQLYCHSTME1Rattus norvegicus
D654AALSHDLDHRG5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
D687EHHHFDQCLMI4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
D687EHHHFDQCLMV1Rattus norvegicus
D764LMTACDLSAIT5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
E682CHSIMEHHHFD4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
E682CHSTMEHHHFD1Rattus norvegicus
E707SGLSIEEYKTT4Homo sapiens, Rattus norvegicus, Bos taurus, Canis lupus familiaris
E707SGLSIDEYKTT1Mus musculus
F559LKITDFSFSDF5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
F786LVATEFFDQGD3Homo sapiens, Bos taurus, Canis lupus familiaris
F786LVAAEFFDQGD2Mus musculus, Rattus norvegicus
F787VATEFFDQGDR3Homo sapiens, Bos taurus, Canis lupus familiaris
F787VAAEFFDQGDR2Mus musculus, Rattus norvegicus
F820SMQVGFIDAIC5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
G697ILNSPGNQILS4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
G697VLNSPGNQILS1Rattus norvegicus
G819PSMQVGFIDAI5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
H613KNVAYHNWRHA5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
H617YHNWRHAFNTA5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
H653IAALSHDLDHR5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
H657SHDLDHRGVNN5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
H678AQLYCHSIMEH4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
H678AQLYCHSTMEH1Rattus norvegicus
H685IMEHHHFDQCL4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
H685TMEHHHFDQCL1Rattus norvegicus
I665VNNSYIQRSEH5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
I680LYCHSIMEHHH4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
I680LYCHSTMEHHH1Rattus norvegicus
I706LSGLSIEEYKT4Homo sapiens, Rattus norvegicus, Bos taurus, Canis lupus familiaris
I706LSGLSIDEYKT1Mus musculus
I729DLALYIKRRGE5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
I768CDLSAITKPWP5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
I778PIQQRIAELVA5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
I813EKKNKIPSMQV5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
I824GFIDAICLQLY5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
K730LALYIKRRGEF5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
L690HFDQCLMILNS4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
L690HFDQCLMVLNS1Rattus norvegicus
L693QCLMILNSPGN4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
L693QCLMVLNSPGN1Rattus norvegicus
L701PGNQILSGLSI5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
L704QILSGLSIEEY4Homo sapiens, Rattus norvegicus, Bos taurus, Canis lupus familiaris
L704QILSGLSIDEY1Mus musculus
L725ILATDLALYIK5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
L765MTACDLSAITK5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
L804MEPADLMNREK2Mus musculus, Rattus norvegicus
L804IEPADLMNREK2Bos taurus, Canis lupus familiaris
L804IEPTDLMNREK1Homo sapiens
M816NKIPSMQVGFI5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
N661DHRGVNNSYIQ5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
N662HRGVNNSYIQR5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
P696MILNSPGNQIL4Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris
P696MVLNSPGNQIL1Rattus norvegicus
Q666NNSYIQRSEHP5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
Q699NSPGNQILSGL5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
Q775KPWPIQQRIAE5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
Q817KIPSMQVGFID5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
S560KITDFSFSDFE5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
S663RGVNNSYIQRS5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
S668SYIQRSEHPLA5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
S702GNQILSGLSIE4Homo sapiens, Rattus norvegicus, Bos taurus, Canis lupus familiaris
S702GNQILSGLSID1Mus musculus
S705ILSGLSIEEYK4Homo sapiens, Rattus norvegicus, Bos taurus, Canis lupus familiaris
S705ILSGLSIDEYK1Mus musculus
T723QAILATDLALY5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
V782RIAELVATEFF3Homo sapiens, Bos taurus, Canis lupus familiaris
V782RIAELVAAEFF2Mus musculus, Rattus norvegicus
Y612RKNVAYHNWRH5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
Y664GVNNSYIQRSE5Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, Canis lupus familiaris
Y709LSIEEYKTTLK4Homo sapiens, Rattus norvegicus, Bos taurus, Canis lupus familiaris
Y709LSIDEYKTTLK1Mus musculus


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