1. Gene Aliases

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

CXCL12-activated CXCR4 signaling pathway [The series of molecular signals initiated by the binding of the C-X-C chemokine CXCL12 to a C-X-C chemokine type 4 receptor (CXCR4) on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. GO:0038160]

amyloid-beta clearance [The process in which amyloid-beta is removed from extracellular brain regions by mechanisms involving cell surface receptors. GO:0097242]

amyloid-beta clearance by cellular catabolic process [The process in which amyloid-beta is removed from extracellular brain regions by cell surface receptor-mediated endocytosis, followed by intracellular degradation. GO:0150094]

apoptotic cell clearance [The recognition and removal of an apoptotic cell by a neighboring cell or by a phagocyte.|Note that unlike mammals or Drosophila, C. elegans (and many lower organisms) do not have professional macrophages/phagocytes, instead cell corpses are engulfed by neighboring cells. Cell types that can function as engulfing cells include hypodermal cells, gonadal sheath cells, pharyngeal muscle cells, and intestinal cells. GO:0043277]

astrocyte activation [A change in morphology and behavior of an astrocyte resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. GO:0048143]

cellular response to amyloid-beta [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a amyloid-beta stimulus. GO:1904646]

cellular response to glucose stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus. GO:0071333]

cellular response to hypoxia [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.|Note that this term should not be confused with 'cellular response to anoxia ; GO:0071454'. Note that in laboratory studies, hypoxia is typically studied at O2 concentrations ranging from 0.1 - 5%. GO:0071456]

cellular response to lipid [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipid stimulus. GO:0071396]

cellular response to lipoteichoic acid [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipoteichoic acid stimulus; lipoteichoic acid is a major component of the cell wall of gram-positive bacteria and typically consists of a chain of glycerol-phosphate repeating units linked to a glycolipid anchor. GO:0071223]

cellular response to oxidised low-density lipoprotein particle stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an oxidized lipoprotein particle stimulus. GO:0140052]

cellular response to peptidoglycan [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptidoglycan stimulus. Peptidoglycan is a bacterial cell wall macromolecule. GO:0071224]

complement-mediated synapse pruning [Synaptic pruning mediated by complement system signaling. GO:0150062]

defense response to Gram-negative bacterium [Reactions triggered in response to the presence of a Gram-negative bacterium that act to protect the cell or organism. GO:0050829]

defense response to bacterium [Reactions triggered in response to the presence of a bacterium that act to protect the cell or organism. GO:0042742]

dendritic cell differentiation [The process in which a precursor cell type acquires the specialized features of a dendritic cell. A dendritic cell is a leukocyte of dendritic lineage specialized in the uptake, processing, and transport of antigens to lymph nodes for the purpose of stimulating an immune response via T cell activation.|Note that immunologists typically use the word 'maturation' to refer to dendritic cells undergoing the process that GO describes as 'cell differentiation'. GO:0097028]

dendritic spine maintenance [The organization process that preserves a dendritic spine in a stable functional or structural state. A dendritic spine is a specialized protrusion from a neuronal dendrite and is involved in synaptic transmission. GO:0097062]

detection of lipopolysaccharide [The series of events in which a lipopolysaccharide stimulus is received by a cell and converted into a molecular signal. Lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0032497]

detection of lipoteichoic acid [The series of events in which a lipoteichoic acid stimulus is received by a cell and converted into a molecular signal; lipoteichoic acid is a major component of the cell wall of gram-positive bacteria and typically consists of a chain of glycerol-phosphate repeating units linked to a glycolipid anchor. GO:0070392]

detection of peptidoglycan [The series of events in which a peptidoglycan stimulus is received by a cell and converted into a molecular signal. Peptidoglycan is a bacterial cell wall macromolecule. GO:0032499]

excitatory synapse pruning [The disaggregation of an excitatory synapse into its constituent components. GO:1905805]

import into cell [The directed movement of some substance from outside of a cell into a cell. This may occur via transport across the plasma membrane or via endocytosis. GO:0098657]

lipid homeostasis [Any process involved in the maintenance of an internal steady state of lipid within an organism or cell. GO:0055088]

memory [The activities involved in the mental information processing system that receives (registers), modifies, stores, and retrieves informational stimuli. The main stages involved in the formation and retrieval of memory are encoding (processing of received information by acquisition), storage (building a permanent record of received information as a result of consolidation) and retrieval (calling back the stored information and use it in a suitable way to execute a given task). GO:0007613]

microglial cell activation [The change in morphology and behavior of a microglial cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. GO:0001774]

microglial cell activation involved in immune response [The change in morphology and behavior of a microglial cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor, leading to the initiation or perpetuation of an immune response. GO:0002282]

microglial cell proliferation [The expansion of a microglial cell population by cell division. GO:0061518]

negative regulation of NLRP3 inflammasome complex assembly [Any process that stops, prevents or reduces the frequency, rate or extent of NLRP3 inflammasome complex assembly. GO:1900226]

negative regulation of amyloid fibril formation [Any process that stops, prevents or reduces the frequency, rate or extent of amyloid fibril formation.|Although deposition of amyloid fibrils is associated with diseases, e.g. Alzheimer's disease, amyloid formation is a normal process. Disease occurs when the balance between amyloid formation and clearance is disrupted (reviewed e.g. in PMID: 29654159 and PMID: 28937655). An example of a normal amyloid complex is composed of human RIP1 and RIP3 kinases (PMID: 22817896). GO:1905907]

negative regulation of apoptotic process [Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.|This term should only be used when it is not possible to determine which phase or subtype of the apoptotic process is negatively regulated by a gene product. Whenever detailed information is available, the more granular children terms should be used. GO:0043066]

negative regulation of astrocyte activation [Any process that decreases the frequency, rate or extent of astrocyte activation. GO:0061889]

negative regulation of autophagic cell death [Any process that stops, prevents or reduces the frequency, rate or extent of autophagic cell death. GO:1904093]

negative regulation of autophagy [Any process that stops, prevents, or reduces the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. GO:0010507]

negative regulation of canonical NF-kappaB signal transduction [Any process that stops, prevents, or reduces the frequency, rate or extent of a canonical NF-kappaB signaling cascade. GO:0043124]

negative regulation of cell activation [Any process that stops, prevents, or reduces the frequency, rate or extent of cell activation. GO:0050866]

negative regulation of cholesterol storage [Any process that decreases the rate or extent of cholesterol storage. Cholesterol storage is the accumulation and maintenance in cells or tissues of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. GO:0010887]

negative regulation of cytokine production involved in inflammatory response [Any process that stops, prevents or reduces the frequency, rate or extent of cytokine production involved in inflammatory response. GO:1900016]

negative regulation of fat cell proliferation [Any process that stops or decreases the rate or extent of fat cell proliferation. GO:0070345]

negative regulation of glial cell apoptotic process [Any process that stops, prevents, or reduces the frequency, rate, or extent of glial cell apoptotic process. GO:0034351]

negative regulation of inflammatory response to antigenic stimulus [Any process that stops, prevents, or reduces the frequency, rate, or extent of an inflammatory response to an antigenic stimulus. GO:0002862]

negative regulation of interleukin-1 beta production [Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-1 beta production. GO:0032691]

negative regulation of macrophage colony-stimulating factor signaling pathway [Any process that stops, prevents or reduces the frequency, rate or extent of macrophage colony-stimulating factor signaling pathway. GO:1902227]

negative regulation of neuroinflammatory response [Any process that stops, prevents or reduces the frequency, rate or extent of neuroinflammatory response. GO:0150079]

negative regulation of p38MAPK cascade [Any process that stops, prevents or reduces the frequency, rate or extent of p38MAPK cascade. GO:1903753]

negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [Any process that stops, prevents, or reduces the frequency, rate or extent of phosphatidylinositol 3-kinase/protein kinase B signal transduction. GO:0051898]

negative regulation of sequestering of triglyceride [Any process that decreases the rate, frequency or extent of sequestering of triglyceride. Triglyceride sequestration is the process of binding or confining any triester of glycerol such that it is separated from other components of a biological system. GO:0010891]

negative regulation of toll-like receptor 2 signaling pathway [Any process that stops, prevents, or reduces the frequency, rate, or extent of toll-like receptor 2 signaling pathway. GO:0034136]

negative regulation of toll-like receptor 4 signaling pathway [Any process that stops, prevents, or reduces the frequency, rate, or extent of toll-like receptor 4 signaling pathway. GO:0034144]

negative regulation of tumor necrosis factor production [Any process that stops, prevents, or reduces the frequency, rate, or extent of tumor necrosis factor production.|Note that this term refers only to the specific, original 'tumor necrosis factor' protein (TNF) and not other members of the tumor necrosis factor superfamily (those with the gene symbol root 'TNFSF'). GO:0032720]

neuroinflammatory response [The immediate defensive reaction by neural vertebrate tissue to infection or injury caused by chemical or physical agents. GO:0150076]

osteoclast differentiation [The process in which a relatively unspecialized monocyte acquires the specialized features of an osteoclast. An osteoclast is a specialized phagocytic cell associated with the absorption and removal of the mineralized matrix of bone tissue. GO:0030316]

phagocytosis, engulfment [The internalization of bacteria, immune complexes and other particulate matter or of an apoptotic cell by phagocytosis, including the membrane and cytoskeletal processes required, which involves one of three mechanisms: zippering of pseudopods around a target via repeated receptor-ligand interactions, sinking of the target directly into plasma membrane of the phagocytosing cell, or induced uptake via an enhanced membrane ruffling of the phagocytosing cell similar to macropinocytosis. GO:0006911]

phagocytosis, recognition [The initial step in phagocytosis involving adhesion to bacteria, immune complexes and other particulate matter, or an apoptotic cell and based on recognition of factors such as bacterial cell wall components, opsonins like complement and antibody or protein receptors and lipids like phosphatidyl serine, and leading to intracellular signaling in the phagocytosing cell.|Note that cell surface molecules involved in the direct binding of bacteria may be also annotated to the molecular function term 'bacterial cell surface binding ; GO:0051635'. Note that cell surface molecules involved in the direct binding to opsonins such as complement components or antibodies may be also annotated to the term 'opsonin binding ; GO:0001846'. GO:0006910]

positive regulation of ATP biosynthetic process [Any process that activates or increases the frequency, rate or extent of ATP biosynthetic process. GO:2001171]

positive regulation of C-C chemokine receptor CCR7 signaling pathway [Any process that activates or increases the frequency, rate or extent of C-C chemokine receptor CCR7 signaling pathway. GO:1903082]

positive regulation of CAMKK-AMPK signaling cascade [Any process that activates or increases the frequency, rate or extent of CAMKK-AMPK signaling cascade. GO:1905291]

positive regulation of CD40 signaling pathway [Any process that activates or increases the frequency, rate or extent of signaling via the CD40 signaling pathway. GO:2000350]

positive regulation of ERK1 and ERK2 cascade [Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. GO:0070374]

positive regulation of TOR signaling [Any process that activates or increases the frequency, rate or extent of TOR signaling. GO:0032008]

positive regulation of amyloid-beta clearance [Any process that activates or increases the frequency, rate or extent of amyloid-beta clearance. GO:1900223]

positive regulation of antigen processing and presentation of peptide antigen via MHC class II [Any process that activates or increases the frequency, rate, or extent of antigen processing and presentation of peptide antigen via MHC class II. GO:0002588]

positive regulation of calcium-mediated signaling [Any process that activates or increases the frequency, rate or extent of calcium-mediated signaling. GO:0050850]

positive regulation of chemotaxis [Any process that activates or increases the frequency, rate or extent of the directed movement of a motile cell or organism in response to a specific chemical concentration gradient. GO:0050921]

positive regulation of cholesterol efflux [Any process that increases the frequency, rate or extent of cholesterol efflux. Cholesterol efflux is the directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle. GO:0010875]

positive regulation of complement activation, classical pathway [Any process that activates or increases the frequency, rate or extent of complement activation by the classical pathway. GO:0045960]

positive regulation of engulfment of apoptotic cell [Any process that activates or increases the frequency, rate or extent of engulfment of apoptotic cell. GO:1901076]

positive regulation of establishment of protein localization [Any process that activates or increases the frequency, rate or extent of establishment of protein localization. GO:1904951]

positive regulation of gene expression [Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). GO:0010628]

positive regulation of high-density lipoprotein particle clearance [Any process that increases the rate, frequency or extent of high-density lipoprotein particle clearance. High-density lipoprotein particle clearance is the process in which a high-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded. GO:0010983]

positive regulation of interleukin-10 production [Any process that activates or increases the frequency, rate, or extent of interleukin-10 production. GO:0032733]

positive regulation of low-density lipoprotein particle clearance [Any process that activates or increases the frequency, rate or extent of low-density lipoprotein particle clearance. GO:1905581]

positive regulation of macrophage fusion [Any process that activates or increases the frequency, rate or extent of macrophage fusion. GO:0034241]

positive regulation of microglial cell activation [Any process that activates or increases the frequency, rate or extent of microglial cell activation. GO:1903980]

positive regulation of microglial cell migration [Any process that activates or increases the frequency, rate or extent of microglial cell migration. GO:1904141]

positive regulation of mitochondrion organization [Any process that increases the frequency, rate or extent of a process involved in the formation, arrangement of constituent parts, or disassembly of a mitochondrion. GO:0010822]

positive regulation of neuroinflammatory response [Any process that activates or increases the frequency, rate or extent of neuroinflammatory response. GO:0150078]

positive regulation of non-canonical NF-kappaB signal transduction [Any process that activates or increases the frequency, rate or extent of the non-canonical NF-kappaB cascade. GO:1901224]

positive regulation of osteoclast differentiation [Any process that activates or increases the frequency, rate or extent of osteoclast differentiation. GO:0045672]

positive regulation of peptidyl-tyrosine phosphorylation [Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine. GO:0050731]

positive regulation of phagocytosis [Any process that activates or increases the frequency, rate or extent of phagocytosis. GO:0050766]

positive regulation of phagocytosis, engulfment [Any process that activates or increases the frequency, rate or extent of the internalization of bacteria, immune complexes and other particulate matter or of an apoptotic cell by phagocytosis. GO:0060100]

positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [Any process that activates or increases the frequency, rate or extent of phosphatidylinositol 3-kinase/protein kinase B signal transduction. GO:0051897]

positive regulation of proteasomal protein catabolic process [Any process that activates or increases the frequency, rate or extent of proteasomal protein catabolic process. GO:1901800]

positive regulation of protein localization to plasma membrane [Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane. GO:1903078]

positive regulation of protein phosphorylation [Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein. GO:0001934]

positive regulation of protein secretion [Any process that activates or increases the frequency, rate or extent of the controlled release of a protein from a cell. GO:0050714]

positive regulation of synapse pruning [Any process that activates or increases the frequency, rate or extent of synapse pruning. GO:1905808]

pyroptosis [A caspase-1-dependent cell death subroutine that is associated with the generation of pyrogenic mediators such as IL-1beta and IL-18. GO:0070269]

regulation of TOR signaling [Any process that modulates the frequency, rate or extent of TOR signaling. GO:0032006]

regulation of cytokine production involved in inflammatory response [Any process that modulates the frequency, rate or extent of cytokine production involved in inflammatory response. GO:1900015]

regulation of gene expression [Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).|This class covers any process that regulates the rate of production of a mature gene product, and so includes processes that regulate that rate by regulating the level, stability or availability of intermediates in the process of gene expression. For example, it covers any process that regulates the level, stability or availability of mRNA or circRNA for translation and thereby regulates the rate of production of the encoded protein via translation. GO:0010468]

regulation of hippocampal neuron apoptotic process [Any process that modulates the occurrence or rate of cell death by apoptotic process in hippocampal neurons. GO:0110089]

regulation of innate immune response [Any process that modulates the frequency, rate or extent of the innate immune response, the organism's first line of defense against infection. GO:0045088]

regulation of interleukin-6 production [Any process that modulates the frequency, rate, or extent of interleukin-6 production. GO:0032675]

regulation of intracellular signal transduction [Any process that modulates the frequency, rate or extent of intracellular signal transduction. GO:1902531]

regulation of lipid metabolic process [Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving lipids. GO:0019216]

regulation of macrophage inflammatory protein 1 alpha production [Any process that modulates the frequency, rate, or extent of production of macrophage inflammatory protein 1 alpha. GO:0071640]

regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway [Any process that modulates the frequency, rate or extent of oxidative stress-induced neuron intrinsic apoptotic signaling pathway. GO:1903376]

regulation of peptidyl-tyrosine phosphorylation [Any process that modulates the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine. GO:0050730]

regulation of plasma membrane bounded cell projection organization [Any process that modulates the frequency, rate or extent of a process involved in the formation, arrangement of constituent parts, or disassembly of plasma membrane bounded cell projections. GO:0120035]

regulation of resting membrane potential [Any process that modulates the establishment or extent of a resting potential, the electrical charge across the plasma membrane, with the interior of the cell negative with respect to the exterior. The resting potential is the membrane potential of a cell that is not stimulated to be depolarized or hyperpolarized. GO:0060075]

regulation of toll-like receptor 6 signaling pathway [Any process that modulates the frequency, rate, or extent of toll-like receptor 6 signaling pathway. GO:0034151]

respiratory burst after phagocytosis [A phase of elevated metabolic activity, during which oxygen consumption increases, that occurs in neutrophils, monocytes, and macrophages shortly after phagocytosing material. An enhanced uptake of oxygen leads to the production, by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals, which play a part in microbiocidal activity. GO:0045728]

response to axon injury [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an axon injury stimulus. GO:0048678]

response to ischemia [Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a inadequate blood supply.|Ischemia always results in hypoxia; however, hypoxia can occur without ischemia. GO:0002931]

social behavior [Behavior directed towards society, or taking place between members of the same species. Occurs predominantly, or only, in individuals that are part of a group.|Behavior such as predation which involves members of different species is not social. Communication between members of different species is also not social behavior. GO:0035176]

MSigDB Signatures:

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

REACTOME_ADAPTIVE_IMMUNE_SYSTEM: Adaptive Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ADAPTIVE_IMMUNE_SYSTEM.html]

REACTOME_DEVELOPMENTAL_BIOLOGY: Developmental Biology [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DEVELOPMENTAL_BIOLOGY.html]

REACTOME_NERVOUS_SYSTEM_DEVELOPMENT: Nervous system development [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NERVOUS_SYSTEM_DEVELOPMENT.html]

REACTOME_DAP12_SIGNALING: DAP12 signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DAP12_SIGNALING.html]

WP_MICROGLIA_PATHOGEN_PHAGOCYTOSIS_PATHWAY: Microglia pathogen phagocytosis pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_MICROGLIA_PATHOGEN_PHAGOCYTOSIS_PATHWAY.html]

REACTOME_IMMUNOREGULATORY_INTERACTIONS_BETWEEN_A_LYMPHOID_AND_A_NON_LYMPHOID_CELL: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_IMMUNOREGULATORY_INTERACTIONS_BETWEEN_A_LYMPHOID_AND_A_NON_LYMPHOID_CELL.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

GeneCards Summary: TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) is a Protein Coding gene. Diseases associated with TREM2 include Polycystic Lipomembranous Osteodysplasia With Sclerosing Leukoencephalopathy 2 and Polycystic Lipomembranous Osteodysplasia With Sclerosing Leukoencephalopathy 1. Among its related pathways are Nervous system development and DAP12 interactions. Gene Ontology (GO) annotations related to this gene include signaling receptor activity and lipopolysaccharide binding. An important paralog of this gene is CD300E.

UniProtKB/Swiss-Prot Summary: Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding [PMID: 10799849]. Acts as a receptor for amyloid-beta protein 42, a cleavage product of the amyloid-beta precursor protein APP, and mediates its uptake and degradation by microglia [PMID: 27477018, PMID: 29518356]. Binding to amyloid-beta 42 mediates microglial activation, proliferation, migration, apoptosis and expression of pro-inflammatory cytokines, such as IL6R and CCL3, and the anti-inflammatory cytokine ARG1. Acts as a receptor for lipoprotein particles such as LDL, VLDL, and HDL and for apolipoproteins such as APOA1, APOA2, APOB, APOE, APOE2, APOE3, APOE4, and CLU and enhances their uptake in microglia [PMID: 27477018]. Binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and sphingomyelin [PMID: 29794134]. Regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade. Required for microglial phagocytosis of apoptotic neurons [PMID: 24990881]. Also required for microglial activation and phagocytosis of myelin debris after neuronal injury and of neuronal synapses during synapse elimination in the developing brain. Regulates microglial chemotaxis and process outgrowth, and also the microglial response to oxidative stress and lipopolysaccharide. It suppresses PI3K and NF-kappa-B signaling in response to lipopolysaccharide; thus promoting phagocytosis, suppressing pro-inflammatory cytokine and nitric oxide production, inhibiting apoptosis and increasing expression of IL10 and TGFB. During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling. Plays a role in microglial MTOR activation and metabolism. Regulates age-related changes in microglial numbers [PMID: 29752066]. Triggers activation of the immune responses in macrophages and dendritic cells [PMID: 10799849]. Mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages. In dendritic cells, it mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival [PMID: 11602640]. Involved in the positive regulation of osteoclast differentiation [PMID: 12925681].

8. Cellular Location of Gene Product

Cytoplasmic and membranous expression in several tissues. Localized to vesicles. Predicted location: Secreted, Membrane (different isoforms) [https://www.proteinatlas.org/ENSG00000095970/subcellular]

9. Mechanistic Information

Summary

TREM2 enhances the phagocytic activity of both microglia in the brain and macrophages in peripheral tissues, including the lung, contributing to the functional removal of cellular debris and potentially limiting the release of pro-inflammatory cytokines indirectly through these phagocytic processes. TREM2's capacity to bind anionic phospholipids like phosphatidylserine, a component of cell membranes typically exposed on the surface of apoptotic cells, facilitates the recognition and ingestion of these cells by immune cells. The recognition and management of such phospholipids via TREM2 thus plays an instrumental role in maintaining pulmonary surfactant homeostasis, particularly under conditions of lung injury where disrupted alveolar cells might otherwise accumulate and impair gas exchange.

In lung diseases, such as COPD, IPF, and in response to bleomycin or ovalbumin challenge, TREM2 upregulation plays a key role in the recruitment and activation of immune cells that attempt to remove cellular debris and manage inflammation, part of an innate response to lung injury. This upregulated expression of TREM2 correlates with decreased lung function and negative clinical outcomes, likely because the enhanced immune response and macrophage activity could contribute to further inflammation and tissue damage when not properly resolved. In the case of bacterial infections in the lung, TREM2 aids in the clearance of bacteria, and its absence exacerbates inflammation, indicating that TREM2's function is crucial for resolving infections and minimizing tissue damage.

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: brain, choroid plexus (tissue enhanced) [https://www.proteinatlas.org/ENSG00000095970/tissue]

Cell type enchanced: hofbauer cells (cell type enriched) [https://www.proteinatlas.org/ENSG00000095970/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

No biomarkers associated with disease or organ of interest were found