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 PDE9A

Gene summary

Basic gene Info.	Gene symbol	PDE9A
	Gene name	phosphodiesterase 9A
	Synonyms	HSPDE9A2
	Cytomap	UCSC genome browser: 21q22.3
	Type of gene	protein-coding
	RefGenes	NM_001001567.1, NM_001001568.1,NM_001001569.1,NM_001001570.1,NM_001001571.1, NM_001001572.1,NM_001001573.1,NM_001001574.1,NM_001001575.1, NM_001001576.1,NM_001001577.1,NM_001001578.1,NM_001001579.1, NM_001001580.1,NM_001001581.1,NM_001001582.1,NM_001001583.1, NM_001001584.2,NM_001001585.1,NM_002606.2,
	Description	CGMP-specific 3',5'-cyclic phosphodiesterase type 9high affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9Aphosphodiesterase PDE9A21
	Modification date	20141207
dbXrefs	MIM : 602973
	HGNC : HGNC
	Ensembl : ENSG00000160191
	HPRD : 09115
	Vega : OTTHUMG00000086825
Protein	UniProt: O76083 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PDE9A
	BioGPS: 5152
Pathway	NCI Pathway Interaction Database: PDE9A
	KEGG: PDE9A
	REACTOME: PDE9A
	Pathway Commons: PDE9A
Context	iHOP: PDE9A
	ligand binding site mutation search in PubMed: PDE9A
	UCL Cancer Institute: PDE9A
Assigned class in mutLBSgeneDB	B: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez

GO ID

GO Term

PubMed ID

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Ligand binding site mutations for PDE9A

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

LBS	AAchange of nsSNV	Cancer type	# samples
D353	D353N	COAD	1
Y484	E483K	SKCM	1
G515	G515E	SKCM	1
H356	H356Y	SKCM	1
I514	I514F	STAD	1

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 PDE9A

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.

LBS	AAchange of nsSNV	Relative stability change
Y484	E483K	-1.8511971
I514	I514F	-1.1001034
H356	H356Y	-0.99912714
D353	D353N	-0.28714321
G515	G515E	-0.094698767

(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 PDE9A from PDB

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Differential gene expression and gene-gene network for PDE9A

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 PDE9A and the right PPI network was created from samples without mutations in the LBS of PDE9A. 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 PDE9A

Gene level disease information (DisGeNet)

Disease ID

Disease name

# PubMed

Association type

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for PDE9A

Drug information targeting mutLBSgene (Approved drugs only)

Drug status	DrugBank ID	Name	Type	Drug structure
Experimental	DB03597	Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine	Small molecule
Experimental	DB07954	3-isobutyl-1-methyl-7H-xanthine	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PDE9A go to BioLip

Ligand ID

Ligand short name

Ligand long name

PDB ID

PDB name

mutLBS

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Conservation information for LBS of PDE9A

Multiple alignments for O76083 in multiple species

LBS	AA sequence	# species	Species
A512	VTKATAQIGFI	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
D304	LFCVHDNYRNN	2	Homo sapiens, Pan troglodytes
D304	LLCVHDNYRNN	1	Mus musculus
D304	LLCVHDNYRSN	1	Rattus norvegicus
D353	AAICHDLDHPG	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
D462	LIKCCDISNEV	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
E382	DISPLENHHCA	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
F311	YRNNPFHNFRH	3	Homo sapiens, Pan troglodytes, Mus musculus
F311	YRSNPFHNFRH	1	Rattus norvegicus
F485	LLEEYFMQSDR	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
F501	LPVAPFMDRDK	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
F516	TAQIGFIKFVL	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
G515	ATAQIGFIKFV	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
H312	RNNPFHNFRHC	3	Homo sapiens, Pan troglodytes, Mus musculus
H312	RSNPFHNFRHC	1	Rattus norvegicus
H316	FHNFRHCFCVA	2	Homo sapiens, Pan troglodytes
H316	FHNFRHCFCVT	2	Mus musculus, Rattus norvegicus
H352	TAAICHDLDHP	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
H356	CHDLDHPGYNN	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
H385	PLENHHCAVAF	2	Homo sapiens, Pan troglodytes
H385	PLENHHCAIAF	2	Mus musculus, Rattus norvegicus
I463	IKCCDISNEVR	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
I514	KATAQIGFIKF	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
L480	PWVDCLLEEYF	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
L481	WVDCLLEEYFM	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
M425	ILATDMARHAE	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
M502	PVAPFMDRDKV	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
N465	CCDISNEVRPM	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
Q513	TKATAQIGFIK	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
T423	TLILATDMARH	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
T511	KVTKATAQIGF	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
V477	VAEPWVDCLLE	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
V520	GFIKFVLIPMF	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
Y306	CVHDNYRNNPF	3	Homo sapiens, Pan troglodytes, Mus musculus
Y306	CVHDNYRSNPF	1	Rattus norvegicus
Y484	CLLEEYFMQSD	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus