mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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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 PDE4A
Gene summary
Basic gene Info.Gene symbolPDE4A
Gene namephosphodiesterase 4A, cAMP-specific
SynonymsDPDE2|PDE4|PDE46
CytomapUCSC genome browser: 19p13.2
Type of geneprotein-coding
RefGenesNM_001111307.1,
NM_001111308.1,NM_001111309.1,NM_001243121.1,NM_006202.2,
DescriptioncAMP-specific 3',5'-cyclic phosphodiesterase 4Aphosphodiesterase 4A, cAMP-specific (duncephosphodiesterase E2 dunce homolog, Drosophilaphosphodiesterase isozyme 4
Modification date20141207
dbXrefs MIM : 600126
HGNC : HGNC
Ensembl : ENSG00000065989
HPRD : 02527
Vega : OTTHUMG00000180411
ProteinUniProt: P27815
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PDE4A
BioGPS: 5141
PathwayNCI Pathway Interaction Database: PDE4A
KEGG: PDE4A
REACTOME: PDE4A
Pathway Commons: PDE4A
ContextiHOP: PDE4A
ligand binding site mutation search in PubMed: PDE4A
UCL Cancer Institute: PDE4A
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:0006198cAMP catabolic process17404263


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Ligand binding site mutations for PDE4A
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
D591A590VGBM1
D474D474NHNSC1
F613Q615HKIRC1
D474V475LLUAD1
N594N594SSTAD1
H473A471VUCEC1
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 PDE4A
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
F613Q615H-1.0745272
D474V475L-0.90902103
N594N594S-0.73330091
H473A471V-0.4219737
D474D474N-0.40433243
D591A590V-0.3834742
(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 PDE4A from PDB

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Differential gene expression and gene-gene network for PDE4A
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 PDE4A and the right PPI network was created from samples without mutations in the LBS of PDE4A. 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 PDE4A
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0004352Autistic Disorder1Biomarker

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

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Pharmacological information for PDE4A
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
ApprovedDB00277TheophyllineSmall molecule
ApprovedDB00651DyphyllineSmall molecule
Approved|investigationalDB00806PentoxifyllineSmall molecule
ApprovedDB00824EnprofyllineSmall molecule
ApprovedDB00920KetotifenSmall molecule
ApprovedDB00975DipyridamoleSmall molecule
Approved|investigationalDB01088IloprostSmall molecule
ApprovedDB01303OxtriphyllineSmall molecule
ApprovedDB01656RoflumilastSmall molecule
ExperimentalDB01791PiclamilastSmall molecule
InvestigationalDB05219AN2728Small molecule
Approved|investigationalDB05266IbudilastSmall molecule
Approved|investigationalDB05676ApremilastSmall molecule
InvestigationalDB05876PDE4Small molecule
ApprovedDB06751DrotaverineSmall molecule
ExperimentalDB06842(4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-oneSmall molecule
ExperimentalDB082994-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acidSmall molecule
ApprovedDB08811TofisopamSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PDE4A go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS


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Conservation information for LBS of PDE4A
Multiple alignments for P27815 in multiple species
LBSAA sequence# speciesSpecies
D429DHYHADVAYHN3Homo sapiens, Mus musculus, Rattus norvegicus
D474AAAIHDVDHPG3Homo sapiens, Mus musculus, Rattus norvegicus
D591MVHCADLSNPT3Homo sapiens, Mus musculus, Rattus norvegicus
F613RIMAEFFQQGD3Homo sapiens, Mus musculus, Rattus norvegicus
F645KSQVGFIDYIV3Homo sapiens, Mus musculus, Rattus norvegicus
H427LEDHYHADVAY3Homo sapiens, Mus musculus, Rattus norvegicus
H433ADVAYHNSLHA3Homo sapiens, Mus musculus, Rattus norvegicus
H437YHNSLHAADVL3Homo sapiens, Mus musculus, Rattus norvegicus
H473FAAAIHDVDHP3Homo sapiens, Mus musculus, Rattus norvegicus
I609QWTDRIMAEFF3Homo sapiens, Mus musculus, Rattus norvegicus
M546VLATDMSKHMT3Homo sapiens, Mus musculus, Rattus norvegicus
M610WTDRIMAEFFQ3Homo sapiens, Mus musculus, Rattus norvegicus
M630MEISPMCDKHT3Homo sapiens, Mus musculus, Rattus norvegicus
N594CADLSNPTKPL3Homo sapiens, Mus musculus, Rattus norvegicus
Q642SVEKSQVGFID3Homo sapiens, Mus musculus, Rattus norvegicus
S641ASVEKSQVGFI3Homo sapiens, Mus musculus, Rattus norvegicus
T544DMVLATDMSKH3Homo sapiens, Mus musculus, Rattus norvegicus
T606LYRQWTDRIMA3Homo sapiens, Mus musculus, Rattus norvegicus
Y432HADVAYHNSLH3Homo sapiens, Mus musculus, Rattus norvegicus


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