TREM2: Triggering Receptor Expressed on Myeloid Cells 2
Key Immune Receptor in Alzheimer's Disease and Neuroinflammation
Gene Information Card
| Symbol | TREM2 |
|---|---|
| Full Name | Triggering Receptor Expressed on Myeloid Cells 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 54209 ncbi.nlm.nih.gov/gene/54209 |
| Ensembl ID | ENSG00000095970 |
| UniProt ID | Q9NZC2 |
| OMIM ID | 605086 |
| HGNC ID | 17761 |
| Aliases | PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c |
Description
TREM2 encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily. It is expressed on myeloid cells such as microglia, macrophages, and osteoclasts. TREM2 forms a receptor-signaling complex with TYROBP (DAP12) and regulates immune responses, phagocytosis, and cell survival. Loss-of-function mutations cause Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL) and increase risk for late-onset Alzheimer's disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease (late-onset) | TREM2 variants (e.g., R47H) impair microglial function, reducing Aβ clearance and promoting neuroinflammation | GWAS, functional studies (PMID: 24097068, 24162737) |
| Nasu-Hakola disease (PLOSL) | Biallelic loss-of-function mutations in TREM2 or TYROBP disrupt osteoclast and microglial signaling, leading to bone cysts and neurodegeneration | OMIM #221770, ClinVar |
| Frontotemporal dementia | TREM2 variants may contribute to TDP-43 pathology and microglial dysfunction | Case-control studies (PMID: 25284779) |
| Parkinson's disease | Rare TREM2 variants associated with increased risk in some populations | Meta-analysis (PMID: 28886341) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (microglia) | 12.5 | High |
| Lung (alveolar macrophages) | 8.3 | Medium |
| Spleen | 6.1 | Medium |
| Blood (monocytes) | 4.7 | Low |
| Bone marrow | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Microglia (iPS-derived) | 15.2 | High expression |
| THP-1 (monocyte) | 9.8 | Medium expression |
| U937 (macrophage) | 7.4 | Medium expression |
| HEK293 | 0.5 | Very low / not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R47H (rs75932628) | Missense | ~0.3% (European) | Increased risk for Alzheimer's disease; impaired ligand binding and microglial function |
| R62H (rs143332484) | Missense | ~0.1% | Moderate risk for Alzheimer's disease |
| Q33X (rs104894002) | Nonsense | Rare | Loss-of-function; causes Nasu-Hakola disease |
| Y38C (rs201258663) | Missense | Rare | Loss-of-function; associated with PLOSL |
| T96K (rs2234255) | Missense | ~1% | Reduced TREM2 shedding; possible protective effect |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function (e.g., Q33X, Y38C) cause Nasu-Hakola disease; heterozygous loss-of-function variants (e.g., R47H) increase Alzheimer's risk by impairing microglial phagocytosis and survival.
Gain of Function (GOF)
Not well established; some variants (e.g., T96K) may reduce shedding and increase surface expression, but functional impact is unclear.
Dominant Negative (DN)
R47H may act as a dominant-negative by disrupting TREM2 dimerization and signaling, though haploinsufficiency is also proposed.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004888 – transmembrane signaling receptor activity | • GO:0007165 – signal transduction |
| • GO:0006909 – phagocytosis | • GO:0045087 – innate immune response |
| • GO:0030674 – protein binding | • bridging |
| • GO:0005886 – plasma membrane |
Pathways
• TREM2 signaling (Reactome: R-HSA-2172127)
• Microglia pathogen phagocytosis pathway (KEGG: hsa04650)
• Osteoclast differentiation (KEGG: hsa04380)
• Alzheimer's disease (KEGG: hsa05010)
Protein Summary
TREM2 is a 230-amino-acid type I transmembrane protein with a single extracellular immunoglobulin-like domain, a stalk region, a transmembrane domain containing a lysine residue for DAP12 interaction, and a short cytoplasmic tail. It is primarily expressed on microglia in the brain and on osteoclasts. Upon ligand binding (e.g., anionic lipids, ApoE, Aβ), TREM2 associates with TYROBP to activate SYK and PI3K pathways, promoting cell survival, proliferation, and phagocytosis. Soluble TREM2 (sTREM2) is generated by ADAM10/17 shedding and is a biomarker for microglial activation in neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| Trem2 Knockout BV-2 Cell Line | EDC07598 | Mouse | 83433 | Details Get a Quote |
| TREM2 Knockout HEK293 Cell Line | EDJ-KQ1140 | Human | 54209 | Details Get a Quote |
| TREM2 Overexpression BV-2 Stable Cell Line | EDC90074 | Mouse | 54209 | Details Get a Quote |
| TREM2 Knockout THP-1 Cell Line | EDJ-KZ61 | Human | 54209 | Details Get a Quote |
| TREM2 Knockout HeLa Cell Line | EDJ-KQ56402 | Human | 54209 | Details Get a Quote |
| TREM2 Knockout A-549 Cell Line | EDJ-KQ64894 | Human | 54209 | Details Get a Quote |
| TREM2 Knockout HCT 116 Cell Line | EDJ-KQ73338 | Human | 54209 | Details Get a Quote |
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