TLR4
toll like receptor 4 | ARMD10, CD284, TLR-4, hToll

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. In silico studies have found a particularly strong binding of surface TLR4 with the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease-2019 (COVID-19). This receptor has also been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness, and with susceptibility to age-related macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

Biological processes 164 terms
MyD88-dependent toll-like receptor signaling pathway (GO:0002755)MyD88-dependent toll-like receptor signaling pathway (GO:0002755)MyD88-dependent toll-like receptor signaling pathway (GO:0002755)MyD88-dependent toll-like receptor signaling pathway (GO:0002755)T-helper 1 type immune response (GO:0042088)TRIF-dependent toll-like receptor signaling pathway (GO:0035666)TRIF-dependent toll-like receptor signaling pathway (GO:0035666)amyloid-beta binding (GO:0001540)cell surface (GO:0009986)cellular response to amyloid-beta (GO:1904646)cellular response to amyloid-beta (GO:1904646)cellular response to lipopolysaccharide (GO:0071222)cellular response to lipopolysaccharide (GO:0071222)cellular response to lipopolysaccharide (GO:0071222)cellular response to lipopolysaccharide (GO:0071222)cellular response to mechanical stimulus (GO:0071260)cellular response to oxidised low-density lipoprotein particle stimulus (GO:0140052)cellular response to oxidised low-density lipoprotein particle stimulus (GO:0140052)cellular response to oxidised low-density lipoprotein particle stimulus (GO:0140052)cellular response to platelet-derived growth factor stimulus (GO:0036120)cellular response to type II interferon (GO:0071346)cytoplasm (GO:0005737)cytoplasm (GO:0005737)defense response to Gram-negative bacterium (GO:0050829)defense response to Gram-negative bacterium (GO:0050829)defense response to bacterium (GO:0042742)defense response to bacterium (GO:0042742)detection of fungus (GO:0016046)detection of lipopolysaccharide (GO:0032497)detection of lipopolysaccharide (GO:0032497)detection of lipopolysaccharide (GO:0032497)detection of stimulus (GO:0051606)early endosome (GO:0005769)endosome membrane (GO:0010008)endosome membrane (GO:0010008)external side of plasma membrane (GO:0009897)identical protein binding (GO:0042802)immune response (GO:0006955)immune response (GO:0006955)inflammatory response (GO:0006954)inflammatory response (GO:0006954)inflammatory response (GO:0006954)innate immune response (GO:0045087)innate immune response (GO:0045087)innate immune response (GO:0045087)intestinal epithelial structure maintenance (GO:0060729)intestinal epithelial structure maintenance (GO:0060729)leukocyte activation (GO:0045321)lipopolysaccharide binding (GO:0001530)lipopolysaccharide binding (GO:0001530)lipopolysaccharide binding (GO:0001530)lipopolysaccharide immune receptor activity (GO:0001875)lipopolysaccharide immune receptor activity (GO:0001875)lipopolysaccharide receptor complex (GO:0046696)lipopolysaccharide receptor complex (GO:0046696)lipopolysaccharide-mediated signaling pathway (GO:0031663)lipopolysaccharide-mediated signaling pathway (GO:0031663)macrophage activation (GO:0042116)membrane (GO:0016020)negative regulation of ERK1 and ERK2 cascade (GO:0070373)negative regulation of ERK1 and ERK2 cascade (GO:0070373)negative regulation of cold-induced thermogenesis (GO:0120163)negative regulation of cold-induced thermogenesis (GO:0120163)negative regulation of interleukin-17 production (GO:0032700)negative regulation of interleukin-17 production (GO:0032700)negative regulation of interleukin-23 production (GO:0032707)negative regulation of interleukin-23 production (GO:0032707)negative regulation of interleukin-6 production (GO:0032715)negative regulation of interleukin-6 production (GO:0032715)negative regulation of osteoclast differentiation (GO:0045671)negative regulation of tumor necrosis factor production (GO:0032720)negative regulation of tumor necrosis factor production (GO:0032720)negative regulation of type II interferon production (GO:0032689)negative regulation of type II interferon production (GO:0032689)perinuclear region of cytoplasm (GO:0048471)phagocytic cup (GO:0001891)phagocytosis (GO:0006909)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)positive regulation of NLRP3 inflammasome complex assembly (GO:1900227)positive regulation of NLRP3 inflammasome complex assembly (GO:1900227)positive regulation of canonical NF-kappaB signal transduction (GO:0043123)positive regulation of canonical NF-kappaB signal transduction (GO:0043123)positive regulation of canonical NF-kappaB signal transduction (GO:0043123)positive regulation of canonical NF-kappaB signal transduction (GO:0043123)positive regulation of cellular response to macrophage colony-stimulating factor stimulus (GO:1903974)positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343)positive regulation of chemokine production (GO:0032722)positive regulation of chemokine production (GO:0032722)positive regulation of cytokine production involved in inflammatory response (GO:1900017)positive regulation of cytokine production involved in inflammatory response (GO:1900017)positive regulation of cytokine production involved in inflammatory response (GO:1900017)positive regulation of cytokine production involved in inflammatory response (GO:1900017)positive regulation of extrinsic apoptotic signaling pathway (GO:2001238)positive regulation of extrinsic apoptotic signaling pathway (GO:2001238)positive regulation of gene expression (GO:0010628)positive regulation of gene expression (GO:0010628)positive regulation of gene expression (GO:0010628)positive regulation of inflammatory response (GO:0050729)positive regulation of inflammatory response (GO:0050729)positive regulation of inflammatory response (GO:0050729)positive regulation of interferon-alpha production (GO:0032727)positive regulation of interferon-alpha production (GO:0032727)positive regulation of interferon-beta production (GO:0032728)positive regulation of interferon-beta production (GO:0032728)positive regulation of interleukin-1 beta production (GO:0032731)positive regulation of interleukin-1 beta production (GO:0032731)positive regulation of interleukin-1 beta production (GO:0032731)positive regulation of interleukin-1 production (GO:0032732)positive regulation of interleukin-1 production (GO:0032732)positive regulation of interleukin-10 production (GO:0032733)positive regulation of interleukin-10 production (GO:0032733)positive regulation of interleukin-12 production (GO:0032735)positive regulation of interleukin-12 production (GO:0032735)positive regulation of interleukin-12 production (GO:0032735)positive regulation of interleukin-6 production (GO:0032755)positive regulation of interleukin-6 production (GO:0032755)positive regulation of interleukin-6 production (GO:0032755)positive regulation of interleukin-8 production (GO:0032757)positive regulation of macrophage activation (GO:0043032)positive regulation of macrophage activation (GO:0043032)positive regulation of matrix metallopeptidase secretion (GO:1904466)positive regulation of nitric oxide biosynthetic process (GO:0045429)positive regulation of platelet activation (GO:0010572)positive regulation of platelet activation (GO:0010572)positive regulation of reactive oxygen species biosynthetic process (GO:1903428)positive regulation of reactive oxygen species biosynthetic process (GO:1903428)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of tumor necrosis factor production (GO:0032760)positive regulation of tumor necrosis factor production (GO:0032760)positive regulation of tumor necrosis factor production (GO:0032760)positive regulation of tumor necrosis factor production (GO:0032760)positive regulation of type II interferon production (GO:0032729)positive regulation of type II interferon production (GO:0032729)protein binding (GO:0005515)protein heterodimerization activity (GO:0046982)regulation of inflammatory response (GO:0050727)regulation of tumor necrosis factor production (GO:0032680)response to lipopolysaccharide (GO:0032496)response to lipopolysaccharide (GO:0032496)response to lipopolysaccharide (GO:0032496)ruffle (GO:0001726)signal transduction (GO:0007165)signaling receptor activity (GO:0038023)signaling receptor activity (GO:0038023)signaling receptor binding (GO:0005102)signaling receptor complex (GO:0043235)signaling receptor complex (GO:0043235)toll-like receptor 4 signaling pathway (GO:0034142)toll-like receptor 4 signaling pathway (GO:0034142)toll-like receptor 4 signaling pathway (GO:0034142)toll-like receptor signaling pathway (GO:0002224)toll-like receptor signaling pathway (GO:0002224)transmembrane signaling receptor activity (GO:0004888)transmembrane signaling receptor activity (GO:0004888)transmembrane signaling receptor activity (GO:0004888)wound healing involved in inflammatory response (GO:0002246)
Expression (TPM)
TLR4 — as a Regulated Gene

TFs regulating TLR4 0 TFs

Transcription factors with Perturb-seq knockdown data for TLR4. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = TLR4 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to TLR4

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of TLR4, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr9:117,704,154–117,704,620 at TSS At TSS 175
chr9:117,714,402–117,714,570 10.0 kb Proximal (<10kb) 24

Genome Browser

Genomic view of the TLR4 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr9:117,694,154 – 117,724,570
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq