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 TLR8

Gene summary

Basic gene Info.	Gene symbol	TLR8
	Gene name	toll-like receptor 8
	Synonyms	CD288
	Cytomap	UCSC genome browser: Xp22
	Type of gene	protein-coding
	RefGenes	NM_016610.3, NM_138636.5,
	Description	-
	Modification date	20141222
dbXrefs	MIM : 300366
	HGNC : HGNC
	Ensembl : ENSG00000101916
	HPRD : 02296
	Vega : OTTHUMG00000021145
Protein	UniProt: Q9NR97 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_TLR8
	BioGPS: 51311
Pathway	NCI Pathway Interaction Database: TLR8
	KEGG: TLR8
	REACTOME: TLR8
	Pathway Commons: TLR8
Context	iHOP: TLR8
	ligand binding site mutation search in PubMed: TLR8
	UCL Cancer Institute: TLR8
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:0007249	I-kappaB kinase/NF-kappaB signaling	12032557
GO:0009615	response to virus	12032557
GO:0045078	positive regulation of interferon-gamma biosynthetic process	16286015
GO:0045089	positive regulation of innate immune response	16123302
GO:0045356	positive regulation of interferon-alpha biosynthetic process	16286015
GO:0045359	positive regulation of interferon-beta biosynthetic process	16286015

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Ligand binding site mutations for TLR8

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
I634	S633P	COAD	2
H469	H469D	BLCA	1
L605	E606K	BRCA	1
Y353	P354S	COAD	1
I634	S633F	COAD	1
V520	Q519E	LUAD	1
L605	N604Y	OV	1
I634	S633T	OV	1
Y291	Y291C	STAD	1
I341,D343	L342I	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 TLR8

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
L605	E606K	-1.2014189
Y353	P354S	-1.1029228
Y291	Y291C	-1.0623694
H469	H469D	-1.0334977
I341	L342I	-1.0049099
D343	L342I	-1.0049099
I634	S633T	-0.68786572
I634	S633P	-0.57274788
V520	Q519E	-0.51848387
L605	N604Y	-0.50309582
I634	S633F	-0.44792932

(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 TLR8 from PDB

PDB ID	PDB title	PDB structure
3W3G	Crystal structure of human TLR8 (unliganded form)

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Differential gene expression and gene-gene network for TLR8

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 TLR8 and the right PPI network was created from samples without mutations in the LBS of TLR8. 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 TLR8

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0017661	Glomerulonephritis, IGA	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for TLR8

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
Approved\|investigational	DB00724	Imiquimod	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of TLR8 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
UPT		1-[(2R,3AR,4R,6R,6AR)-2-HYDROXY-6-(HYDROXYMETHYL)-2- SULFIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]PYRIMIDINE-2,4(1H,3H)-DIONE	4r09	C	H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r07	A	I341 D343 H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r07	B	I341 D343 H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r07	C	I341 D343 H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r07	D	I341 D343 H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r08	A	I341 D343 H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r08	B	I341 D343 H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r08	C	I341 D343 H469
UCG		3'-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6- DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2- OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4- YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE 5'-(DIHYDROGEN PHOSPHATE)	4r08	D	I341 D343 H469
BU3		(R,R)-BUTANE-2,3-DIOL	3w3g	A	L605 I634
URI		URIDINE	4r07	B	V520
URI		URIDINE	4r07	C	V520
URI		URIDINE	4r07	D	V520
URI		URIDINE	4r08	A	V520
URI		URIDINE	4r08	C	V520
URI		URIDINE	4r09	A	V520
URI		URIDINE	4r09	B	V520
URI		URIDINE	4r09	C	V520
URI		URIDINE	4r09	D	V520
06S		O-[(2R,3S,4R,5R)-5-(2-AMINO-6-OXO-3,6-DIHYDRO-9H-PURIN- 9-YL)-2-({[(S)-({(2R,3S,4R,5R)-5-(2,4-DIOXO-3,4- DIHYDROPYRIMIDIN-1(2H)-YL)-4-HYDROXY-2- [(THIOPHOSPHONOOXY)METHYL]TETRAHYDROFURAN-3-YL}OXY) (SULFANYL)PHOSPHORYL]OXY}METHYL)-4- HYDROXYTETRAHYDROFURAN	4r09	A	Y291 I341 D343 H469
06S		O-[(2R,3S,4R,5R)-5-(2-AMINO-6-OXO-3,6-DIHYDRO-9H-PURIN- 9-YL)-2-({[(S)-({(2R,3S,4R,5R)-5-(2,4-DIOXO-3,4- DIHYDROPYRIMIDIN-1(2H)-YL)-4-HYDROXY-2- [(THIOPHOSPHONOOXY)METHYL]TETRAHYDROFURAN-3-YL}OXY) (SULFANYL)PHOSPHORYL]OXY}METHYL)-4- HYDROXYTETRAHYDROFURAN	4r09	B	Y291 I341 D343 H469
06S		O-[(2R,3S,4R,5R)-5-(2-AMINO-6-OXO-3,6-DIHYDRO-9H-PURIN- 9-YL)-2-({[(S)-({(2R,3S,4R,5R)-5-(2,4-DIOXO-3,4- DIHYDROPYRIMIDIN-1(2H)-YL)-4-HYDROXY-2- [(THIOPHOSPHONOOXY)METHYL]TETRAHYDROFURAN-3-YL}OXY) (SULFANYL)PHOSPHORYL]OXY}METHYL)-4- HYDROXYTETRAHYDROFURAN	4r09	C	Y291 I341 D343 H469
06S		O-[(2R,3S,4R,5R)-5-(2-AMINO-6-OXO-3,6-DIHYDRO-9H-PURIN- 9-YL)-2-({[(S)-({(2R,3S,4R,5R)-5-(2,4-DIOXO-3,4- DIHYDROPYRIMIDIN-1(2H)-YL)-4-HYDROXY-2- [(THIOPHOSPHONOOXY)METHYL]TETRAHYDROFURAN-3-YL}OXY) (SULFANYL)PHOSPHORYL]OXY}METHYL)-4- HYDROXYTETRAHYDROFURAN	4r09	D	Y291 I341 D343 H469
C09	CL097	2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINE	3w3j	A	Y353
C09	CL097	2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINE	3w3j	B	Y353
L07	CL075, 3M-002	2-PROPYL[1,3]THIAZOLO[4,5-C]QUINOLIN-4-AMINE	3w3k	A	Y353
L07	CL075, 3M-002	2-PROPYL[1,3]THIAZOLO[4,5-C]QUINOLIN-4-AMINE	3w3k	B	Y353
RX8	R848, RESIQUIMOD	1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN- 1-YL]-2-METHYLPROPAN-2-OL	3w3l	A	Y353
RX8	R848, RESIQUIMOD	1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN- 1-YL]-2-METHYLPROPAN-2-OL	3w3l	B	Y353
RX8	R848, RESIQUIMOD	1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN- 1-YL]-2-METHYLPROPAN-2-OL	3w3l	C	Y353
RX8	R848, RESIQUIMOD	1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN- 1-YL]-2-METHYLPROPAN-2-OL	3w3l	D	Y353
RX8	R848, RESIQUIMOD	1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN- 1-YL]-2-METHYLPROPAN-2-OL	3w3m	A	Y353
RX8	R848, RESIQUIMOD	1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN- 1-YL]-2-METHYLPROPAN-2-OL	3w3n	A	Y353
RX8	R848, RESIQUIMOD	1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN- 1-YL]-2-METHYLPROPAN-2-OL	3w3n	B	Y353
D87		2-BUTYLFURO[2,3-C]QUINOLIN-4-AMINE	3wn4	A	Y353
D80		2-BUTYL[1,3]OXAZOLO[4,5-C]QUINOLIN-4-AMINE	4qbz	A	Y353
URI		URIDINE	4r07	A	Y353
URI		URIDINE	4r07	B	Y353
URI		URIDINE	4r07	C	Y353
URI		URIDINE	4r07	D	Y353
URI		URIDINE	4r08	A	Y353
URI		URIDINE	4r08	C	Y353
URI		URIDINE	4r08	D	Y353
URI		URIDINE	4r09	A	Y353
URI		URIDINE	4r09	B	Y353
URI		URIDINE	4r09	C	Y353
URI		URIDINE	4r09	D	Y353
URI		URIDINE	4r0a	A	Y353
HB2		1-(4-AMINO-2-BUTYL-1H-IMIDAZO[4,5-C]QUINOLIN-1-YL)-2- METHYLPROPAN-2-OL	4r6a	A	Y353
M0A		1-[[3-(AMINOMETHYL)PHENYL]METHYL]-2-BUTYL-IMIDAZO[4,5- C]QUINOLIN-4-AMINE	5awb	A	Y353
IDQ		1-[[4-(AMINOMETHYL)PHENYL]METHYL]-2-BUTYL-IMIDAZO[4,5- C]QUINOLIN-4-AMINE	5awd	A	Y353

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Conservation information for LBS of TLR8

Multiple alignments for Q9NR97 in multiple species

LBS

AA sequence

# species

Species