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FLASH GENE
Symbol TLR4 contributors: mct/pgu/shn - updated : 18-02-2016
HGNC name toll-like receptor 4
HGNC id 11850
ASSOCIATED DISORDERS
corresponding disease(s)
Other morbid association(s)
TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
tumoral     --low  
in adrenocortical carcinoma
tumoral     --over  
of TLR4 and MYD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer
tumoral     --other  
expressed in ovarian tumor cells specifically of granulosa cell origin
constitutional     --over  
in neonatal Gram-negative (G-) bacteremia
tumoral     --over  
CD74, MIF and TLR4 were found to be expressed in gastric cancer and increased significantly in the advanced stage, and were also associated with lymph node metastasis
constitutional     --low  
significantly lower in Relapsing Remitting Multiple Sclerosis (RRMS) patients than healthy controls
constitutional       gain of function
lead to the development of necrotizing enterocolitis (NEC), a devastating disease of the premature intestine
Susceptibility
  • to severe sepsis following burn injury
  • resistance to legionnaire disease
  • to age-related macular dystrophy
  • Variant & Polymorphism SNP
  • SNP associated with severe sepsis following burn injury
  • SNP A896G or C1196T associated with resistance to legionnaire disease
  • D299G variant increasing the risk of age-related macular dystrophy
  • Candidate gene to new therapies for the prevention and treatment of neuropathic pain syndromes
    Marker
    Therapy target
  • reintroduction of TLR4 expression in adrenocortical carcinoma may provide a novel therapeutic strategy for adrenal cancer
  • ANIMAL & CELL MODELS
  • respiratory syncytial virus persisted longer in the lungs of infected TLR4-deficient mice (
  • TLR4-defective mice subjected to sensitization and pulmonary challenge with a protein allergen had reductions in airway inflammation with eosinophils, allergen-specific IgE levels, and Th2 cytokine production (
  • TLR4 deficiency of bone marrow-derived mast cells in mice resulted in significantly higher mortality because of defective neutrophil recruitment and production of proinflammatory cytokines in the peritoneal cavity (
  • TLR4(+/+) mice receiving TLR4(-/-) bone marrow, 6 weeks after transplant TLR4 was absent in all circulating leukocytes and in resident macrophages , and these cells were completely nonresponsive to lipopolysaccharide
  • TLR4(-/-) mice receiving TLR4(+/+) bone marrow, endothelial cells but not leukocytes were deficient in TLR4, numbers of circulating leukocytes decreased by 90%, and systemic LPS (0.5 mg/kg) induced a dramatic increase in neutrophil sequestration into the lungs (
  • Apolipoprotein E-deficient mice that also lacked TLR4 or MyD88 demonstrated reduced aortic atherosclerosis that was associated with reductions in circulating levels of proinflammatory cytokines IL-12 or monocyte chemoattractant protein 1, plaque lipid content, numbers of macrophage, and cyclooxygenase 2 immunoreactivity in their plaques (