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 AIRE

Gene summary

Basic gene Info.	Gene symbol	AIRE
	Gene name	autoimmune regulator
	Synonyms	AIRE1\|APECED\|APS1\|APSI\|PGA1
	Cytomap	UCSC genome browser: 21q22.3
	Type of gene	protein-coding
	RefGenes	NM_000383.3, NM_000658.2,NM_000659.1,
	Description	autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein
	Modification date	20141221
dbXrefs	MIM : 607358
	HGNC : HGNC
	Ensembl : ENSG00000160224
	HPRD : 06301
	Vega : OTTHUMG00000086921
Protein	UniProt: O43918 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_AIRE
	BioGPS: 326
Pathway	NCI Pathway Interaction Database: AIRE
	KEGG: AIRE
	REACTOME: AIRE
	Pathway Commons: AIRE
Context	iHOP: AIRE
	ligand binding site mutation search in PubMed: AIRE
	UCL Cancer Institute: AIRE
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
GO:0006355	regulation of transcription, DNA-templated	18292755
GO:0045893	positive regulation of transcription, DNA-templated	18292755

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Ligand binding site mutations for AIRE

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
V301,C299	A300V	KIRC	1
C434	G435R	LUAD	1
L308	L308V	LUAD	1
I330	E329K	SKCM	1
C434	C434Y	STAD	1
C322	L323M	STAD	1
C449	A450T	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 AIRE

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
I330	E329K	-1.0104748
L308	L308V	-0.9592469
C322	L323M	-0.81611639
C449	A450T	-0.67996762
V301	A300V	-0.5758284
C299	A300V	-0.5758284
C434	G435R	-0.56068792
C434	C434Y	-0.098320946

(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 AIRE from PDB

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Differential gene expression and gene-gene network for AIRE

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

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C3494489	Autoimmune polyendocrinopathy syndrome, type 1	63	Biomarker, GeneticVariation
umls:C0085859	Polyglandular autoimmune syndrome type I	57	Biomarker, GeneticVariation
umls:C0085409	Polyendocrinopathies, Autoimmune	18	Biomarker, GeneticVariation
umls:C0006840	Candidiasis	14	Biomarker, GeneticVariation

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for AIRE

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 AIRE go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
ZN		ZINC(2+)	1xwh	A	C299 V301 C322
ZN		ZINC(2+)	2ke1	A	C299 V301 C322
ZN		ZINC(2+)	2kft	A	C299 V301 C322
III		Peptide ligand (ALA,ARG,THR,LYS,GLN,THR,ALA,ARG,LYS,SER)	2ke1	A	L308 I330
III		Peptide ligand (ALA,ARG,THR,LYS,GLN,THR,ALA,ARG,LYS,SER,THR,GLY,GLY,LYS,ALA,PRO,ARG,LYS,GLN,LEU,CYS)	2kft	A	L308 I330

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Conservation information for LBS of AIRE

Multiple alignments for O43918 in multiple species

LBS

AA sequence

# species

Species