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 PDE4B
Gene summary
Basic gene Info.Gene symbolPDE4B
Gene namephosphodiesterase 4B, cAMP-specific
SynonymsDPDE4|PDEIVB
CytomapUCSC genome browser: 1p31
Type of geneprotein-coding
RefGenesNM_001037339.2,
NM_001037340.2,NM_001037341.1,NM_001297440.1,NM_001297441.1,
NM_001297442.1,NM_002600.3,
DescriptioncAMP-specific 3',5'-cyclic phosphodiesterase 4Bdunce-like phosphodiesterase E4phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)
Modification date20141207
dbXrefs MIM : 600127
HGNC : HGNC
Ensembl : ENSG00000184588
HPRD : 02528
Vega : OTTHUMG00000009088
ProteinUniProt: Q07343
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PDE4B
BioGPS: 5142
PathwayNCI Pathway Interaction Database: PDE4B
KEGG: PDE4B
REACTOME: PDE4B
Pathway Commons: PDE4B
ContextiHOP: PDE4B
ligand binding site mutation search in PubMed: PDE4B
UCL Cancer Institute: PDE4B
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 PDE4B
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
Y575R576WBLCA1
I622I622TBRCA1
L565L565QCOAD1
H450H450YGBM1
F618,I622D620NHNSC1
H410A412SLUAD1
L565L565VOV1
H410,H406S408NSTAD1
I582R581HSTAD1
Y405V403MSTAD1
Y405V403MUCEC1
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 PDE4B
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
I622I622T-1.4833735
L565L565Q-1.4690279
H410A412S-1.4022767
L565L565V-1.2725479
F618D620N-1.237174
I622D620N-1.237174
I582R581H-1.0258777
Y575R576W-0.91807461
H450H450Y-0.89749846
Y405V403M-0.63431684
H406S408N-0.50241061
H410S408N-0.50241061
(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 PDE4B from PDB

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Differential gene expression and gene-gene network for PDE4B
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 PDE4B and the right PPI network was created from samples without mutations in the LBS of PDE4B. 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 PDE4B
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0036341Schizophrenia18AlteredExpression, Biomarker, GeneticVariation
umls:C0005586Bipolar Disorder3Biomarker
umls:C0004096Asthma3Biomarker
umls:C0001973Alcoholism2Biomarker, GeneticVariation
umls:C0004352Autistic Disorder1Biomarker
umls:C0236733Amphetamine-Related Disorders1Biomarker
umls:C0311375Arsenic Poisoning1Biomarker
umls:C0023467Leukemia, Myeloid, Acute1Biomarker
umls:C0151744Myocardial Ischemia1Biomarker
umls:C0037274Skin Diseases1Biomarker

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

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Pharmacological information for PDE4B
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|nutraceuticalDB00131Adenosine monophosphateSmall molecule
ApprovedDB00201CaffeineSmall molecule
ApprovedDB00277TheophyllineSmall molecule
ApprovedDB00651DyphyllineSmall molecule
Approved|investigationalDB00806PentoxifyllineSmall molecule
ApprovedDB00824EnprofyllineSmall molecule
ApprovedDB00920KetotifenSmall molecule
Approved|investigationalDB01088IloprostSmall molecule
ApprovedDB01113PapaverineSmall molecule
ApprovedDB01412TheobromineSmall molecule
ApprovedDB01427AmrinoneSmall molecule
ExperimentalDB01647(R)-MesopramSmall molecule
ApprovedDB01656RoflumilastSmall molecule
ExperimentalDB01791PiclamilastSmall molecule
ExperimentalDB01954RolipramSmall molecule
ExperimentalDB019593,5-Dimethyl-1-(3-Nitrophenyl)-1h-Pyrazole-4-Carboxylic Acid Ethyl EsterSmall molecule
ExperimentalDB02660FilaminastSmall molecule
ExperimentalDB033498-Bromo-Adenosine-5'-MonophosphateSmall molecule
ExperimentalDB03606(S)-RolipramSmall molecule
ExperimentalDB038071-(2-Chlorophenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl EsterSmall molecule
InvestigationalDB03849CilomilastSmall molecule
ExperimentalDB04149(R)-RolipramSmall molecule
ExperimentalDB04530S,S-(2-Hydroxyethyl)ThiocysteineSmall molecule
InvestigationalDB05219AN2728Small molecule
Approved|investigationalDB05266IbudilastSmall molecule
Approved|investigationalDB05676ApremilastSmall molecule
ExperimentalDB069091-ethyl-N-(phenylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideSmall molecule
ExperimentalDB082994-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acidSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PDE4B go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
9888-(3-NITROPHENYL)-6-(PYRIDIN-4-YLMETHYL)QUINOLINE3g45BH406 I582 F618
9888-(3-NITROPHENYL)-6-(PYRIDIN-4-YLMETHYL)QUINOLINE3g45AH406 L565 I582 F618
ZNZINC(2+)3g45AH410
ZNZINC(2+)3g45BH410
ZNZINC(2+)4myqAH410
ZNZINC(2+)4nw7AH410
ZNZINC(2+)4wziAH410
ZNZINC(2+)4wziBH410
ZNZINC(2+)4x0fAH410
ZNZINC(2+)4x0fBH410
19T(4-{[2-(5-CHLOROTHIOPHEN-2-YL)-5-ETHYL-6- METHYLPYRIMIDIN-4-YL]AMINO}PHENYL)ACETIC ACID4myqAY405 I582 F618
ROLROLIPRAM4x0fAY405 Y575 I582 F618
ROLROLIPRAM4x0fBY405 Y575 I582 F618
2O5(4-{[4-(3-CHLOROPHENYL)-6-CYCLOPROPYL-1,3,5-TRIAZIN-2- YL]AMINO}PHENYL)ACETIC ACID4nw7AY575 I582 F618


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Conservation information for LBS of PDE4B
Multiple alignments for Q07343 in multiple species
LBSAA sequence# speciesSpecies


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