Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

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Basic Info

Approved Symbol	TLR4
Symbol Alias	hToll, CD284, TLR-4, ARMD10
Approved Name	toll-like receptor 4
Location	9q33.1
Position	chr9:117704332-117716871, 1
External Links	HGNC: 11850 Entrez Gene: 7099 Ensembl: ENSG00000136869 UCSC: uc004bjz.4
No. of Studies	1 (Positive: 1; Negative: 0; trend: 0)
Overlap with SZ?	NO
Overlap with MDD?	NO

Gene related studies (count: 1)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Oliveira, J., 2013	SNP: rs1927914, rs11536891	We report for the first time a genetic association between BD and TLR-4 a major player of innate immunity. Possible mechanisms underlying bipolar disorders linking altered TLR-4 expression and increased susceptibility to infections and/or autoimmunity are discussed.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 77)

GO terms by PBA (count: 5)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0045087	innate immune response	biological process	TAS[15356140]	49
GO:0005886	plasma membrane	cellular component	IDA[19740627]; TAS	360
GO:0030890	positive regulation of B cell proliferation	biological process	IEA	3
GO:0004872	receptor activity	molecular function	TAS[10426995]	19
GO:0005887	integral component of plasma membrane	cellular component	IDA[15027902]	158

GO terms by database search (count: 72)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0042088	T-helper 1 type immune response	biological process	NAS[11970998]	1
GO:0001875	lipopolysaccharide receptor activity	molecular function	IDA[19252480]	1
GO:0005515	protein binding	molecular function	IPI[11441107]	563
GO:0042116	macrophage activation	biological process	IMP[10835634]	1
GO:0071223	cellular response to lipoteichoic acid	biological process	IEA	2
GO:0032757	positive regulation of interleukin-8 production	biological process	IDA[19740627]	2
GO:0032707	negative regulation of interleukin-23 production	biological process	ISS	2
GO:0002322	B cell proliferation involved in immune response	biological process	IEA	2
GO:0007249	I-kappaB kinase/NF-kappaB signaling	biological process	TAS	2
GO:0032735	positive regulation of interleukin-12 production	biological process	ISS	5
GO:0048471	perinuclear region of cytoplasm	cellular component	IDA[15027902]	50
GO:0032700	negative regulation of interleukin-17 production	biological process	ISS	2
GO:0035666	TRIF-dependent toll-like receptor signaling pathway	biological process	TAS	7
GO:0032729	positive regulation of interferon-gamma production	biological process	ISS	7
GO:0045416	positive regulation of interleukin-8 biosynthetic process	biological process	IDA[17951129]	2
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process	biological process	ISS	4
GO:0034134	toll-like receptor 2 signaling pathway	biological process	TAS	8
GO:0032722	positive regulation of chemokine production	biological process	IDA[19740627]	4
GO:0051092	positive regulation of NF-kappaB transcription factor activity	biological process	IDA[12594207]	12
GO:0042535	positive regulation of tumor necrosis factor biosynthetic process	biological process	IDA[17951129]	1
GO:0071222	cellular response to lipopolysaccharide	biological process	ISS	12
GO:0042742	defense response to bacterium	biological process	TAS[10426995]	4
GO:0031663	lipopolysaccharide-mediated signaling pathway	biological process	IDA[10880523]; IGI[10880523]	6
GO:0007252	I-kappaB phosphorylation	biological process	IDA[19740627]	1
GO:0046696	lipopolysaccharide receptor complex	cellular component	IDA[19252480]	1
GO:0001530	lipopolysaccharide binding	molecular function	IMP[16514062]; NAS[10835634]	2
GO:0002537	nitric oxide production involved in inflammatory response	biological process	IEA	1
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	ISS	91
GO:0032496	response to lipopolysaccharide	biological process	IC[16514062]; IDA[12594207]	22
GO:0034142	toll-like receptor 4 signaling pathway	biological process	TAS	8
GO:0045671	negative regulation of osteoclast differentiation	biological process	NAS[12133979]	4
GO:0045359	positive regulation of interferon-beta biosynthetic process	biological process	IEA	1
GO:0002224	toll-like receptor signaling pathway	biological process	TAS	10
GO:0010572	positive regulation of platelet activation	biological process	ISS[16514062]	1
GO:0046330	positive regulation of JNK cascade	biological process	IEA	4
GO:0032497	detection of lipopolysaccharide	biological process	IDA[19252480]	1
GO:0060729	intestinal epithelial structure maintenance	biological process	ISS	1
GO:0050707	regulation of cytokine secretion	biological process	IEA	1
GO:0034138	toll-like receptor 3 signaling pathway	biological process	TAS	7
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway	biological process	TAS	8
GO:0050729	positive regulation of inflammatory response	biological process	IC[19740627]	6
GO:0045429	positive regulation of nitric oxide biosynthetic process	biological process	IEA	13
GO:0006955	immune response	biological process	TAS[10426995]	19
GO:0070430	positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	biological process	IEA	1
GO:0070374	positive regulation of ERK1 and ERK2 cascade	biological process	IEA	14
GO:0042346	positive regulation of NF-kappaB import into nucleus	biological process	IDA[19740627]	4
GO:0032755	positive regulation of interleukin-6 production	biological process	IDA[19740627]	8
GO:0070373	negative regulation of ERK1 and ERK2 cascade	biological process	ISS	4
GO:0032732	positive regulation of interleukin-1 production	biological process	ISS	1
GO:0004888	transmembrane signaling receptor activity	molecular function	NAS[11970998]	10
GO:0045348	positive regulation of MHC class II biosynthetic process	biological process	IEA	5
GO:0032728	positive regulation of interferon-beta production	biological process	ISS	1
GO:0032733	positive regulation of interleukin-10 production	biological process	ISS	1
GO:0032760	positive regulation of tumor necrosis factor production	biological process	ISS	5
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway	biological process	TAS	8
GO:0002756	MyD88-independent toll-like receptor signaling pathway	biological process	TAS	7
GO:0071260	cellular response to mechanical stimulus	biological process	IEP[19593445]	12
GO:0070434	positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	biological process	IEA	1
GO:0032727	positive regulation of interferon-alpha production	biological process	ISS	1
GO:0010008	endosome membrane	cellular component	TAS	17
GO:0045084	positive regulation of interleukin-12 biosynthetic process	biological process	IDA[15027902]	2
GO:0016046	detection of fungus	biological process	NAS[11254600]	1
GO:0002755	MyD88-dependent toll-like receptor signaling pathway	biological process	TAS	8
GO:0000187	activation of MAPK activity	biological process	ISS	14
GO:0009897	external side of plasma membrane	cellular component	IDA[16514062]	21
GO:0060907	positive regulation of macrophage cytokine production	biological process	IEA	2
GO:0032609	interferon-gamma production	biological process	IEA	2
GO:0032689	negative regulation of interferon-gamma production	biological process	ISS	2
GO:0005737	cytoplasm	cellular component	IDA[19740627]	322
GO:0050829	defense response to Gram-negative bacterium	biological process	IC[16514062]	3
GO:0032715	negative regulation of interleukin-6 production	biological process	ISS	4
GO:0032720	negative regulation of tumor necrosis factor production	biological process	ISS	5

Gene related KEGG pathways (count: 3)

KEGG pathways by PBA (count: 0)

KEGG pathways by database search (count: 3)

ID	Name	No. of Genes in BDgene
hsa05131	EPEC	6
hsa05130	Pathogenic Escherichia coli infection	6
hsa04620	Toll-like receptor signaling pathway	10

Gene related BioCarta pathways (count: 4)

BioCarta pathways by PBA (count: 0)

BioCarta pathways by database search (count: 4)

ID	Name	No. of Genes in BDgene
tollPathway	Toll-Like Receptor Pathway	2
gsk3Pathway	Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages	5
nfkbPathway	NF-kB Signaling Pathway	2
dcPathway	Dendritic cells in regulating TH1 and TH2 Development	3

Gene related interactors from protein-protein interactions data in HPRD (count: 21)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
TLR4	TIRAP	NO	in vivo	11526399
TLR4	CNPY4	NO	in vitro;in vivo	16338228
TLR4	BCL10	NO	in vivo	15213237
TLR4	IRAK1	NO	in vivo	9625770
TLR4	RNF216	NO	yeast 2-hybrid	15107846
TLR4	TLR1	NO	in vivo	11932926
TLR4	DEFB4	NO	in vitro;in vivo	12411706
TLR4	RIPK2	NO	in vivo	15691841
TLR4	BTK	NO	yeast 2-hybrid	12724322
TLR4	SYK	NO	in vivo	14699155
TLR4	TICAM2	NO	in vitro;in vivo;yeast 2-hybrid	14519765 , 14556004 , 14517278
TLR4	TLR5	NO	in vitro;in vivo	12794153
TLR4	MYD88	NO	in vivo	10952994 , 11743586
TLR4	SIGIRR	NO	in vivo	12925853
TLR4	CD14	NO	in vivo	12196527
TLR4	MAPK8IP3	NO	in vivo	12941697
TLR4	LY96	NO	in vivo	11976338 , 10359581
TLR4	HMGB1	NO	in vivo	16267105
TLR4	IRAK2	NO	in vivo	9625770
TLR4	NOX4	NO	in vitro;yeast 2-hybrid	15356101
TLR4	TOLLIP	NO	in vivo	11751856

Related other genetic factors

Gene related SNPs (count: 6)

Literature-origin SNPs (count: 2)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs1927914	chr9:117702447 - 117702447(1)	upstream_gene_variant	1(1/0/0)
rs11536891	chr9:117717059 - 117717059(1)	downstream_gene_variant	1(1/0/0)

LD-proxies (count: 4)

rs_ID	Location	Functional Annotation
rs10116253	chr9:117702042 - 117702042(1)	upstream_gene_variant
rs2737190	chr9:117701903 - 117701903(1)	upstream_gene_variant
rs1927911	chr9:117707776 - 117707776(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2149356	chr9:117711921 - 117711921(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant; upstream_gene_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 0)

Gene related regions (count: 3)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
Chr 9	chr9:0-138394717	3 (0/3/0)
9q33	chr9:114900000-127500000	1 (0/0/1)
9q32-q33	chr9:112100000-127500000	1 (0/0/1)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)

Gene relationship with SZ

Gene relationship with MDD

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Region: chr9:117704332..117716871 View in gBrowse