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 PIK3C3

Gene summary

Basic gene Info.	Gene symbol	PIK3C3
	Gene name	phosphatidylinositol 3-kinase, catalytic subunit type 3
	Synonyms	VPS34\|hVps34
	Cytomap	UCSC genome browser: 18q12.3
	Type of gene	protein-coding
	RefGenes	NM_002647.2,
	Description	PI3-kinase type 3PI3K type 3PtdIns-3-kinase type 3phosphatidylinositol 3-kinase catalytic subunit type 3phosphatidylinositol 3-kinase p100 subunitphosphoinositide-3-kinase, class 3
	Modification date	20141207
dbXrefs	MIM : 602609
	HGNC : HGNC
	HPRD : 04009
Protein	UniProt: Q8NEB9 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PIK3C3
	BioGPS: 5289
Pathway	NCI Pathway Interaction Database: PIK3C3
	KEGG: PIK3C3
	REACTOME: PIK3C3
	Pathway Commons: PIK3C3
Context	iHOP: PIK3C3
	ligand binding site mutation search in PubMed: PIK3C3
	UCL Cancer Institute: PIK3C3
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 PIK3C3

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
D761	G763R	BLCA	1
S614	S614N	COAD	1
L750	T752R	HNSC	1
S687	S687L	LUAD	1
S614,P618	L616R	UCEC	1
D644	Q645R	UCEC	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 PIK3C3

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
P618	L616R	-1.550773
S614	L616R	-1.550773
L750	T752R	-1.2220179
D761	G763R	-0.80576627
S687	S687L	-0.40264767
D644	Q645R	-0.29586772
S614	S614N	-0.22818916

(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 PIK3C3 from PDB

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Differential gene expression and gene-gene network for PIK3C3

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 PIK3C3 and the right PPI network was created from samples without mutations in the LBS of PIK3C3. 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 PIK3C3

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 PIK3C3

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 status	DrugBank ID	Name	Type	Drug structure
Experimental	DB06836	N-(5-(4-CHLORO-3-(2-HYDROXY-ETHYLSULFAMOYL)- PHENYLTHIAZOLE-2-YL)-ACETAMIDE	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PIK3C3 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
AJZ		3-(4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENOL	3ls8	B	D644 D761
AJZ		3-(4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENOL	3ls8	A	D644 S687 L750 D761
UJB		(2S)-1-[(5-CHLORO-2-THIENYL)METHYL]-8-[(3R, 5R)-3,5-DIMETHYLMORPHOLIN-4-YL]-2- (TRIFLUOROMETHYL)-3,4-DIHYDRO-2H-PYRIMIDO[1,2-A]PYRIMI 6-ONE	4uwk	A	P618 L750 D761
1TT		(8S)-9-[(5-CHLORANYLPYRIDIN-3-YL)METHYL]-2-[(3R)-3- METHYLMORPHOLIN-4-YL]-8-(TRIFLUOROMETHYL)-6,7,8,9A- TETRAHYDRO-3H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE	4oys	A	P618 S687 L750
2UG		4'-(CYCLOPROPYLMETHYL)-N~2~-(PYRIDIN-4-YL)-4,5'- BIPYRIMIDINE-2,2'-DIAMINE	4ph4	B	P618 S687 L750
JXM		(8S)-9-[(2R)-2-HYDROXY-2-PHENYLETHYL]-2- (MORPHOLIN-4-YL)-8-(TRIFLUOROMETHYL)-6,7,8,9- TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE	4uwh	A	P618 S687 L750
EUT		(8S)-9-[3,5-BIS(FLUORANYL)PHENYL]-2- MORPHOLIN-4-YL-8-(TRIFLUOROMETHYL)-7,8-DIHYDRO-6H- PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE	4uwf	A	S614 P618 L750
RBQ		(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY) ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9- TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE	4uwg	A	S614 P618 L750
7A5		(8S)-2-[(3R)-3-METHYLMORPHOLIN-4-YL]-9-(3- METHYL-2-OXOBUTYL)-8-(TRIFLUOROMETHYL)-6,7,8,9- TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE	4uwl	A	S614 P618 L750 D761

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Conservation information for LBS of PIK3C3

Multiple alignments for Q8NEB9 in multiple species

LBS	AA sequence	# species	Species
D644	DDLRQDQLILQ	3	Homo sapiens, Mus musculus, Rattus norvegicus
D644	DDLRQDQLVVQ	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Arabidopsis thaliana
D644	DDLRQDQLVIQ	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D747	GDRHLDNLLLT	4	Homo sapiens, Arabidopsis thaliana, Mus musculus, Rattus norvegicus
D747	GDRHLDNLLVT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D747	GDRHLDNLLIT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D761	KLFHIDFGYIL	3	Homo sapiens, Mus musculus, Rattus norvegicus
D761	HFFHADFGYIL	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D761	RLFHVDFAFIL	1	Arabidopsis thaliana
F612	ETATLFKSALM	3	Homo sapiens, Mus musculus, Rattus norvegicus
F612	ETSKVFKSSLS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
F612	DACTVFKSTMQ	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F612	GESSLFKSALH	1	Arabidopsis thaliana
F684	HGFMQFIQSVP	3	Homo sapiens, Mus musculus, Rattus norvegicus
F684	EGAIEFIPNDT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
F684	HGAVQFVPSKT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F684	EGMLEFIPSRS	1	Arabidopsis thaliana
F758	KTGKLFHIDFG	3	Homo sapiens, Mus musculus, Rattus norvegicus
F758	PDGHFFHADFG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
F758	KDGHFFHADFG	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F758	DDGRLFHVDFA	1	Arabidopsis thaliana
I634	GKYPVIFKHGD	3	Homo sapiens, Mus musculus, Rattus norvegicus
I634	QPYHLMFKVGD	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
I634	SKYPIIFKNGD	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I634	GSCKLIFKKGD	1	Arabidopsis thaliana
I685	GFMQFIQSVPV	3	Homo sapiens, Mus musculus, Rattus norvegicus
I685	GAIEFIPNDTL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
I685	GAVQFVPSKTL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I685	GMLEFIPSRSL	1	Arabidopsis thaliana
I760	GKLFHIDFGYI	3	Homo sapiens, Mus musculus, Rattus norvegicus
I760	GHFFHADFGYI	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I760	GRLFHVDFAFI	1	Arabidopsis thaliana
K636	YPVIFKHGDDL	3	Homo sapiens, Mus musculus, Rattus norvegicus
K636	YHLMFKVGDDL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K636	YPIIFKNGDDL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K636	CKLIFKKGDDL	1	Arabidopsis thaliana
L750	HLDNLLLTKTG	3	Homo sapiens, Mus musculus, Rattus norvegicus
L750	HLDNLLVTPDG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L750	HLDNLLITKDG	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L750	HLDNLLLTDDG	1	Arabidopsis thaliana
M682	TKHGFMQFIQS	3	Homo sapiens, Mus musculus, Rattus norvegicus
M682	PQEGAIEFIPN	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
M682	PTHGAVQFVPS	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
M682	HDEGMLEFIPS	1	Arabidopsis thaliana
P618	KSALMPAQLFF	3	Homo sapiens, Mus musculus, Rattus norvegicus
P618	KSSLSPLKITF	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P618	KSTMQPLRLLF	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P618	KSALHPLRLTF	1	Arabidopsis thaliana
P689	FIQSVPVAEVL	3	Homo sapiens, Mus musculus, Rattus norvegicus
P689	FIPNDTLASIL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P689	FVPSKTLATIL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P689	FIPSRSLAQIL	1	Arabidopsis thaliana
Q683	KHGFMQFIQSV	3	Homo sapiens, Mus musculus, Rattus norvegicus
Q683	QEGAIEFIPND	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Q683	THGAVQFVPSK	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q683	DEGMLEFIPSR	1	Arabidopsis thaliana
S614	ATLFKSALMPA	3	Homo sapiens, Mus musculus, Rattus norvegicus
S614	SKVFKSSLSPL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S614	CTVFKSTMQPL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S614	SSLFKSALHPL	1	Arabidopsis thaliana
S687	MQFIQSVPVAE	3	Homo sapiens, Mus musculus, Rattus norvegicus
S687	IEFIPNDTLAS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S687	VQFVPSKTLAT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S687	LEFIPSRSLAQ	1	Arabidopsis thaliana
Y670	LKLTPYKVLAT	3	Homo sapiens, Mus musculus, Rattus norvegicus
Y670	LKLTPYKILAT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y670	LHLKPYRILAT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y670	LCLTPYKVLAT	1	Arabidopsis thaliana