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 APOA1

Gene summary

Basic gene Info.	Gene symbol	APOA1
	Gene name	apolipoprotein A-I
	Synonyms	-
	Cytomap	UCSC genome browser: 11q23-q24
	Type of gene	protein-coding
	RefGenes	NM_000039.1,
	Description	apo-AI
	Modification date	20141222
dbXrefs	MIM : 107680
	HGNC : HGNC
	Ensembl : ENSG00000118137
	HPRD : 02517
	Vega : OTTHUMG00000046112
Protein	UniProt: P02647 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_APOA1
	BioGPS: 335
Pathway	NCI Pathway Interaction Database: APOA1
	KEGG: APOA1
	REACTOME: APOA1
	Pathway Commons: APOA1
Context	iHOP: APOA1
	ligand binding site mutation search in PubMed: APOA1
	UCL Cancer Institute: APOA1
Assigned class in mutLBSgeneDB	C: This gene just belongs to mutLBSgenes.

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

GO ID	GO Term	PubMed ID
GO:0002740	negative regulation of cytokine secretion involved in immune response	12458630
GO:0006656	phosphatidylcholine biosynthetic process	4335615
GO:0007179	transforming growth factor beta receptor signaling pathway	23726972
GO:0007186	G-protein coupled receptor signaling pathway	16443932
GO:0007229	integrin-mediated signaling pathway	23726972
GO:0010804	negative regulation of tumor necrosis factor-mediated signaling pathway	21571275
GO:0010873	positive regulation of cholesterol esterification	4335615
GO:0010903	negative regulation of very-low-density lipoprotein particle remodeling	14967812
GO:0018158	protein oxidation	12576517
GO:0018206	peptidyl-methionine modification	12576517
GO:0030301	cholesterol transport	10559507
GO:0032489	regulation of Cdc42 protein signal transduction	16443932
GO:0033344	cholesterol efflux	11162594
GO:0033700	phospholipid efflux	11162594
GO:0034115	negative regulation of heterotypic cell-cell adhesion	21571275
GO:0034380	high-density lipoprotein particle assembly	190223
GO:0035025	positive regulation of Rho protein signal transduction	23726972
GO:0042632	cholesterol homeostasis	21571275
GO:0050713	negative regulation of interleukin-1 beta secretion	12458630
GO:0050728	negative regulation of inflammatory response	21571275
GO:0050821	protein stabilization	17655203
GO:0050919	negative chemotaxis	23726972
GO:0051345	positive regulation of hydrolase activity	7638166
GO:0051496	positive regulation of stress fiber assembly	23726972
GO:0055091	phospholipid homeostasis	21571275
GO:0060354	negative regulation of cell adhesion molecule production	21571275
GO:0060761	negative regulation of response to cytokine stimulus	21571275
GO:0070328	triglyceride homeostasis	21571275
GO:0070371	ERK1 and ERK2 cascade	23726972
GO:1900026	positive regulation of substrate adhesion-dependent cell spreading	23726972

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Ligand binding site mutations for APOA1

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
E259	E258Q	LUAD	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 APOA1

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
E259	E258Q	-0.40889893

(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 APOA1 from PDB

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Differential gene expression and gene-gene network for APOA1

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 APOA1 and the right PPI network was created from samples without mutations in the LBS of APOA1. 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 APOA1

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C2239176	Carcinoma, Hepatocellular	16	AlteredExpression, Biomarker
umls:C0039292	Tangier Disease	14	Biomarker, GeneticVariation
umls:C0020538	Hypertension	7	Biomarker, GeneticVariation
umls:C1704429	Familial hypoalphalipoproteinemia	7	Biomarker, GeneticVariation
umls:C0038454	Stroke	5	AlteredExpression, Biomarker, GeneticVariation
umls:C0019693	HIV Infections	4	AlteredExpression, Biomarker
umls:C0268389	Amyloidosis, familial visceral	3	Biomarker, GeneticVariation
umls:C0021368	Inflammation	3	Biomarker, GeneticVariation, Therapeutic
umls:C0038356	Stomach Neoplasms	3	Biomarker
umls:C0473527	Hypoalphalipoproteinemias	2	Biomarker, GeneticVariation
umls:C0001418	Adenocarcinoma	2	AlteredExpression, Biomarker
umls:C0024121	Lung Neoplasms	2	AlteredExpression, Biomarker
umls:C0853897	Diabetic Cardiomyopathies	1	Biomarker, Therapeutic
umls:C0242488	Acute Lung Injury	1	Therapeutic
umls:C0152013	Adenocarcinoma of lung	1	Biomarker
umls:C0003130	Anoxia	1	Biomarker
umls:C1848533	Ataxia with vitamin E deficiency	1	Biomarker
umls:C0004943	Behcet Syndrome	1	Biomarker
umls:C0011065	Death	1	Therapeutic
umls:C0011609	Drug Eruptions	1	Biomarker
umls:C0860207	Drug-Induced Liver Injury	1	Biomarker
umls:C0013604	Edema	1	Therapeutic
umls:C0017665	Glomerulonephritis, Membranous	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for APOA1

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.

Drug information targeting mutLBSgene (Approved drugs only)

Drug status

DrugBank ID

Name

Type

Drug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of APOA1 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 APOA1

Multiple alignments for P02647 in multiple species

LBS	AA sequence	# species	Species
A199	LRQRLAARLEA	3	Homo sapiens, Pan troglodytes, Macaca mulatta
A199	VRTKLTERLED	1	Danio rerio
A199	LRQKLSQKLEE	1	Gallus gallus
A199	LRQRLTARLEA	1	Bos taurus
A199	MRENLAQRLTE	1	Rattus norvegicus
A199	MRESLAQRLAE	1	Mus musculus
A200	RQRLAARLEAL	3	Homo sapiens, Pan troglodytes, Macaca mulatta
A200	RTKLTERLEDL	1	Danio rerio
A200	RQKLSQKLEEI	1	Gallus gallus
A200	RQRLTARLEAL	1	Bos taurus
A200	RENLAQRLTEI	1	Rattus norvegicus
A200	RESLAQRLAEL	1	Mus musculus
E222	HAKATEHLSTL	2	Homo sapiens, Pan troglodytes
E222	KEQLVKAVEEA	1	Danio rerio
E222	QAKVMEQLSNL	1	Gallus gallus
E222	HAKASEQLKAL	1	Bos taurus
E222	HAKASEHLSTL	1	Macaca mulatta
E222	HTKASDHLKTL	1	Rattus norvegicus
E222	HTRAKTHLKTL	1	Mus musculus
E259	LSALEEYTKKL	3	Homo sapiens, Pan troglodytes, Macaca mulatta
E259	AQMYETIAKAI	1	Danio rerio
E259	ISFLDELQKSV	1	Gallus gallus
E259	LAAIDEASKKL	1	Bos taurus
E259	MSMIDEAKKKL	1	Rattus norvegicus
E259	QSVIDKASETL	1	Mus musculus
H217	RLAEYHAKATE	2	Homo sapiens, Pan troglodytes
H217	YAEEYKEQLVK	1	Danio rerio
H217	QASEYQAKVME	1	Gallus gallus
H217	-LAEYHAKASE	1	Bos taurus
H217	RLAEYHAKASE	1	Macaca mulatta
H217	TLIEYHTKASD	1	Rattus norvegicus
H217	TLNEYHTRAKT	1	Mus musculus
H223	AKATEHLSTLS	2	Homo sapiens, Pan troglodytes
H223	EQLVKAVEEAR	1	Danio rerio
H223	AKVMEQLSNLR	1	Gallus gallus
H223	AKASEQLKALG	1	Bos taurus
H223	AKASEHLSTLS	1	Macaca mulatta
H223	TKASDHLKTLG	1	Rattus norvegicus
H223	TRAKTHLKTLG	1	Mus musculus
K219	AEYHAKATEHL	2	Homo sapiens, Pan troglodytes
K219	EEYKEQLVKAV	1	Danio rerio
K219	SEYQAKVMEQL	1	Gallus gallus
K219	AEYHAKASEQL	1	Bos taurus
K219	AEYHAKASEHL	1	Macaca mulatta
K219	IEYHTKASDHL	1	Rattus norvegicus
K219	NEYHTRAKTHL	1	Mus musculus
K230	STLSEKAKPAL	3	Homo sapiens, Pan troglodytes, Macaca mulatta
K230	EEAREKIAPHT	1	Danio rerio
K230	SNLREKMTPLV	1	Gallus gallus
K230	KALGEKAKPVL	1	Bos taurus
K230	KTLGEKAKPAL	1	Rattus norvegicus
K230	KTLGEKARPAL	1	Mus musculus
L242	DLRQGLLPVLE	4	Homo sapiens, Bos taurus, Pan troglodytes, Macaca mulatta
L242	DLQTRMEPYME	1	Danio rerio
L242	EFRERLTPYAE	1	Gallus gallus
L242	DLGQGLMPVLE	1	Rattus norvegicus
L242	DLRHSLMPMLE	1	Mus musculus
L243	LRQGLLPVLES	4	Homo sapiens, Bos taurus, Pan troglodytes, Macaca mulatta
L243	LQTRMEPYMEN	1	Danio rerio
L243	FRERLTPYAEN	1	Gallus gallus
L243	LGQGLMPVLEA	1	Rattus norvegicus
L243	LRHSLMPMLET	1	Mus musculus
L246	GLLPVLESFKV	3	Homo sapiens, Pan troglodytes, Macaca mulatta
L246	RMEPYMENVRT	1	Danio rerio
L246	RLTPYAENLKN	1	Gallus gallus
L246	GLLPVLESLKV	1	Bos taurus
L246	GLMPVLEAWKA	1	Rattus norvegicus
L246	SLMPMLETLKT	1	Mus musculus
N208	EALKENGGARL	3	Homo sapiens, Pan troglodytes, Macaca mulatta
N208	EDLRTMAAPYA	1	Danio rerio
N208	EEIREKGIPQA	1	Gallus gallus
N208	EALKEGGGS-L	1	Bos taurus
N208	TEIKNH--PTL	1	Rattus norvegicus
N208	AELKSN--PTL	1	Mus musculus
Q196	SDELRQRLAAR	3	Homo sapiens, Pan troglodytes, Macaca mulatta
Q196	VEAVRTKLTER	1	Danio rerio
Q196	SDELRQKLSQK	1	Gallus gallus
Q196	SDDLRQRLTAR	1	Bos taurus
Q196	SDQMRENLAQR	1	Rattus norvegicus
Q196	SEQMRESLAQR	1	Mus musculus
R195	YSDELRQRLAA	3	Homo sapiens, Pan troglodytes, Macaca mulatta
R195	MVEAVRTKLTE	1	Danio rerio
R195	YSDELRQKLSQ	1	Gallus gallus
R195	YSDDLRQRLTA	1	Bos taurus
R195	YSDQMRENLAQ	1	Rattus norvegicus
R195	HSEQMRESLAQ	1	Mus musculus
R212	ENGGARLAEYH	3	Homo sapiens, Pan troglodytes, Macaca mulatta
R212	TMAAPYAEEYK	1	Danio rerio
R212	EKGIPQASEYQ	1	Gallus gallus
R212	EGGGS-LAEYH	1	Bos taurus
R212	NH--PTLIEYH	1	Rattus norvegicus
R212	SN--PTLNEYH	1	Mus musculus
Y260	SALEEYTKKLN	2	Homo sapiens, Pan troglodytes
Y260	QMYETIAKAIQ	1	Danio rerio
Y260	SFLDELQKSVA	1	Gallus gallus
Y260	AAIDEASKKLN	1	Bos taurus
Y260	SALEEYTKKLS	1	Macaca mulatta
Y260	SMIDEAKKKLN	1	Rattus norvegicus
Y260	SVIDKASETLT	1	Mus musculus