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
nfkbPathway	NF-kB Signaling Pathway	2
gsk3Pathway	Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages	5
dcPathway	Dendritic cells in regulating TH1 and TH2 Development	3
tollPathway	Toll-Like Receptor Pathway	2

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

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

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