gene

TREM2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TREM2: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

3624Connections

30Hypotheses

30Analyses

50Outgoing

50Incoming

Summary

A gene referenced in 1 knowledge graph relationship. Key connections: encodes TREM2_protein (protein).

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🧬 Gene Info

Gene Symbol	TREM2
Full Name	Triggering Receptor Expressed on Myeloid Cells 2
Aliases	TREM-2
Chromosome	6p21.1
Protein Type	Receptor
Target Class	Receptor
Function	Lipid sensing; Debris clearance; Microglial activation
Mechanism of Action	Agonist antibodies that enhance TREM2 signaling to promote microglial function
Primary Expression	Microglia, Cerebral cortex, Hippocampus
Druggability	Low (0.42)
Clinical Stage	Phase II
Molecular Weight	35 kDa
Amino Acids	231 aa
Exons	5
Pathways	Innate immunity, Phagocytosis, DAP12-SYK signaling
UniProt ID	Q9NZC2
NCBI Gene ID	54209
Ensembl ID	ENSG00000095970
OMIM	605086
GeneCards	TREM2
Human Protein Atlas	TREM2
Associated Diseases	ALS, ALZHEIMER'S DISEASE, ALZHEIMERS, AUTOPHAGY, Aging
Known Drugs/Compounds	lecanemab treatment, β-amyloid, phosphatidylserine, Beta-Amyloid, amyloid deposits, METFORMIN
Interactions	NLRP3, TLR4, GSDMD, MYD88, CD9, PSEN1
SciDEX Target	View Target Profile (1 clinical trials)
SciDEX Hypotheses	TREM2-Dependent Microglial Senescence Transition TREM2-Dependent Astrocyte-Microglia Cross-talk in TREM2-Dependent Microglial Phagocytosis Acts as a (+30 more)
KG Connections	3620 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure: TREM2 — PDB 6YXY Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    TREM2["TREM2 Receptor"] -->|"Recognizes"| Ligands["Lipids, Apolipoproteins"]
    TREM2 -->|"Signals via"| DAP12["DAP12 Adapter"]
    DAP12 -->|"Activates"| SYK["SYK Kinase"]
    SYK -->|"Downstream"| PI3K["PI3K/AKT"]
    SYK -->|"Downstream"| MAPK["MAPK Pathway"]
    PI3K -->|"Promotes"| Survival["Cell Survival"]
    MAPK -->|"Induces"| Phagocytosis["Phagocytosis"]
    TREM2 -->|"Modulates"| Inflammation["Inflammatory Response"]
    TREM2 -.Loss-of-function.-> AD["Alzheimer's Risk"]

Outgoing (2035)

Target	Relation	Type	Str
ALZHEIMERS	associated_with	disease	1.00
APOE	activates	protein	1.00
MICROGLIA	expressed_in	cell_type	1.00
MICROGLIA	regulates	cell_type	1.00
Als	activates	disease	1.00
Alzheimer	regulates	disease	1.00
Inflammation	activates	disease	1.00
Neuroinflammation	activates	disease	1.00
Alzheimer	activates	disease	1.00
Alzheimer	associated_with	disease	1.00
Neurodegeneration	associated_with	disease	1.00
Alzheimer	therapeutic_target	disease	1.00
Alzheimer	expressed_in	disease	1.00
Alzheimer	implicated_in	entity	1.00
Neuroinflammation	therapeutic_target	disease	1.00
Inflammation	therapeutic_target	disease	1.00
NEURODEGENERATION	associated_with	disease	1.00
Inflammation	inhibits	disease	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
ALZHEIMER'S DISEASE	activates	gene	1.00
NEUROINFLAMMATION	activates	gene	1.00
ALZHEIMER'S DISEASE	therapeutic_target	gene	1.00
MICROGLIA	activates	gene	1.00
ALZHEIMER	activates	gene	1.00
ALZHEIMER	associated_with	gene	1.00
GENES	associated_with	gene	1.00
ALZHEIMER	therapeutic_target	gene	1.00
MICROGLIA	implicated_in	gene	1.00
ds-f50762b67605	provides_data_for	dataset	1.00
ds-83b31ef18d49	provides_data_for	dataset	1.00
ds-6784494f1741	provides_data_for	dataset	1.00
ds-db4a006ea647	provides_data_for	dataset	1.00
ds-f2c28aed24a7	provides_data_for	dataset	1.00
Phagocytosis	activates	pathway	1.00
ALZHEIMER'S DISEASE	expressed_in	gene	1.00
ALZHEIMER'S DISEASE	regulates	gene	1.00
Immune Response	activates	pathway	1.00
NEUROINFLAMMATION	therapeutic_target	gene	1.00
ALZHEIMER	regulates	gene	1.00
AMYLOID	inhibits	gene	1.00
ALZHEIMER	expressed_in	gene	1.00
PHAGOCYTOSIS	activates	gene	1.00
Late-Onset Alzheimer's Disease	risk_factor_for	disease	0.95
Microglial Metabolism	regulates	process	0.95
NLRP3 Inflammasome Activation	regulates	process	0.95
glioma growth	promotes	process	0.95
GBM progression	prevents	process	0.95
fatty acid oxidation	inhibits	process	0.95
microglia activation	activates	process	0.95
immunosuppression	regulates	process	0.95

Incoming (1589)

Source	Relation	Type	Str
APOE	associated_with	gene	1.00
MICROGLIA	expressed_in	cell_type	1.00
MICROGLIA	associated_with	gene	1.00
MICROGLIA	activates	gene	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
NEURODEGENERATION	associated_with	gene	1.00
AMYLOID	associated_with	protein	1.00
ds-f50762b67605	data_in	dataset	1.00
ds-83b31ef18d49	data_in	dataset	1.00
ds-6784494f1741	data_in	dataset	1.00
ds-db4a006ea647	data_in	dataset	1.00
ds-f2c28aed24a7	data_in	dataset	1.00
TAU	associated_with	gene	0.98
MICROGLIA	inhibits	gene	0.98
PARKINSON'S DISEASE	associated_with	disease	0.98
h-61196ade	targets	hypothesis	0.95
Microglia	expressed_in	cell_type	0.95
anti-TREM2 antibodies	activates	drug	0.90
APOE	activates	gene	0.90
APP	associated_with	gene	0.90
Senescent Microglia	co_expressed_with	cell_type	0.90
Disease-Associated Microglia	associated_with	cell_type	0.90
galectin-3	binds_to	protein	0.90
APOE	ligand_of	gene	0.90
Strem2	associated_with	protein	0.90
ADAM Proteases	mediates	enzyme	0.90
Mutant THAP11	upregulates	protein	0.90
Al002C	activates	drug	0.90
APOE	co_mentioned_with	gene	0.90
NLRP3	co_mentioned_with	gene	0.90
GAL3	interacts_with	protein	0.90
Healthy Microglia-Like Cell Extracellular Vesicles	downregulates	compound	0.90
Rmab38E2-Scfv8D3	upregulates	drug	0.90
ALZHEIMER'S DISEASE	expressed_in	gene	0.90
MICROGLIA	regulates	gene	0.90
TYROBP/DAP12	interacts_with	gene	0.90
MICROGLIA	expresses	cell_type	0.90
h-044ee057	targets_gene	hypothesis	0.90
h-b234254c	targets_gene	hypothesis	0.90
h-seaad-51323624	targets_gene	hypothesis	0.90
h-61196ade	targets_gene	hypothesis	0.90
h-3460f820	targets_gene	hypothesis	0.90
h-180807e5	targets_gene	hypothesis	0.90
h_seaad_001	targets_gene	hypothesis	0.90
h-ea3274ff	targets_gene	hypothesis	0.90
h-e003a35e	targets_gene	hypothesis	0.90
h-7f2d0e21	targets_gene	hypothesis	0.90
h-trem2-3374766c	targets_gene	hypothesis	0.90
h-trem2-883b6abd	targets_gene	hypothesis	0.90
h-trem2-fe8c644a	targets_gene	hypothesis	0.90

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TREM2-Dependent Microglial Senescence Transition	0.692	neurodegeneration	Gene expression changes in aging mouse b
CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Wind	0.674	neuroimmunology	What is the temporal sequence of TREM2 s
TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegen	0.639	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Dependent Microglial Phagocytosis Acts as a Strain Sel	0.636	neurodegeneration	What are the specific molecular determin
Microglial TREM2-SYK Pathway Enhancement	0.626	neurodegeneration	Cell type vulnerability in Alzheimers Di

TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene	0.612	neurodegeneration	Gene expression changes in aging mouse b
TREM2-ASM Crosstalk in Microglial Lysosomal Senescence	0.612	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegener	0.607	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Microglial Clearance Enhancement as Common Mechanism f	0.604	neurodegeneration	Why do p300/CBP inhibitors reduce both A
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc	0.600	neurodegeneration	Gene expression changes in aging mouse b
TREM2-CSF1R Cross-Talk in Microglial Metabolic Reprogramming	0.589	neurodegeneration	Gene expression changes in aging mouse b
H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from	0.588	neurodegeneration	How does APOE4's beneficial immune funct
TREM2-SIRT1 Metabolic Senescence Circuit in Microglial Aging	0.587	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene	0.585	neurodegeneration	Gene expression changes in aging mouse b
TREM2 Agonism to Reprogram Infiltrated Monocytes Toward Neur	0.584	neurodegeneration	What are the specific molecular mechanis
TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene	0.580	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Cholesterol Dysregulation in Microglial Senes	0.574	neurodegeneration	Gene expression changes in aging mouse b
CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microgli	0.569	neurodegeneration	Lipid raft composition changes in synapt
TREM2 Signaling Bifurcation with Independent TYROBP-Independ	0.567	neuroinflammation	Why is TYROBP deficiency neuroprotective
TREM2 R47H Metabolic Lock-in at Cholesterol Ester Accumulati	0.563	neuroimmunology	What is the temporal sequence of TREM2 s
SYK-Independent TREM2 Pathways Remain Functional in TYROBP D	0.555	neuroinflammation	Why is TYROBP deficiency neuroprotective
CLU-APOE-TREM2 Tripartite Axis as a Coordinate Therapeutic T	0.548	neurodegeneration	Does clusterin exacerbate or protect aga
ABCA7-TREM2 Co-Targeting for Microglial Lipid Handling	0.538	neurodegeneration	Why does the V1613M variant reduce amylo
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Sign	0.533	neuroscience	Circuit-level neural dynamics in neurode
TREM2-Mediated Microglial Dysfunction Disrupts Perivascular	0.527	neuroscience	Circuit-level neural dynamics in neurode
Microglial TREM2-Complement Axis Modulation	0.527	neurodegeneration	Cell type vulnerability in Alzheimer's D
TREM2 Agonism to Redirect Microglia from Synaptic Pruning to	0.521	neurodegeneration	How do ALS-associated OPTN mutations mec
Cell-Type Specific TREM2 Upregulation in DAM Microglia	0.519	Alzheimer's Disease	SEA-AD Gene Expression Profiling — Allen
Microglial TREM2 downregulation impairs damage-associated re	0.507	Alzheimer's disease	SEA-AD Single-Cell Analysis: Cell-Type V
TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocy	0.505	neuroinflammation	What molecular mechanisms enable microgl

Mentioning Analyses (30)

Scientific analyses that reference this entity

What is the temporal sequence of TREM2 signaling transition from protective to i

neuroimmunology | 2026-04-15 | 2 hypotheses Top: 0.674

Why is TYROBP deficiency neuroprotective when TYROBP is an adapter for multiple

neuroinflammation | 2026-04-14 | 2 hypotheses Top: 0.567

What are the specific molecular mechanisms by which peripheral monocytes cross t

neurodegeneration | 2026-04-13 | 1 hypotheses Top: 0.584

Can biased TREM2 agonists selectively activate DAP12-SYK-PI3K without triggering

molecular biology | 2026-04-12 | 0 hypotheses

What are the optimal timing windows for TREM2 agonism vs antagonism across disea

neurodegeneration | 2026-04-11 | 0 hypotheses

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Ca [PMID:35642214]	Wang M, Pan W, Xu Y, Zhang J, Wan J, Jia	J Inflamm Res	2022	1
TREM2, microglia, and Alzheimer's disease. [PMID:33516818]	Qin Q, Teng Z, Liu C, Li Q, Yin Y, Tang	Mech Ageing Dev	2021	1
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	1
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease. [PMID:28802038]	Ulland TK, Song WM, Huang SC, Ulrich JD,	Cell	2017	1
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Mic [PMID:28930663]	Krasemann S, Madore C, Cialic R, Baufeld	Immunity	2017	1
Precision Neurodegeneration: Integrating Molecular Mechanisms, Biomarkers, and T [PMID:41833042]	["Lyu G", "Li D"]	CNS & neurological disorders d	2026	0
Emerging pathological mechanisms of Alzheimer's disease pathogenesis: from neuro [PMID:41858793]	["Wang R", "Feng Y", "Zhou Z", "Jiang J"	Frontiers in aging neuroscienc	2026	0
Human CSF proteogenomics links genetic variation to neurodegenerative disease pr [PMID:41757182]	["Puerta R", "Garc\u00eda-Gonz\u00e1lez	medRxiv : the preprint server	2026	0
PLCG2 signaling and genetic resilience in Alzheimer's disease. [PMID:41888907]	Tsai AP, Martin AK, Mi A, Yeh AE, Ramire	Molecular neurodegeneration	2026	0
TREM2 deficiency delays postnatal microglial maturation and synaptic pruning, le [PMID:41930604]	Yang HC, Deng YS, Zhang J, Zhang T, Song	J Alzheimers Dis	2026	0
A scalable human-zebrafish xenotransplantation model reveals gastrosome-mediated [PMID:41957412]	Villani A, Wittmann J, Wyss T, Mallona I	Commun Biol	2026	0
Dual Role of Microglial TREM2 in Neuronal Degeneration and Regeneration After Ax [PMID:41963086]	Pottorf TS, Lane EL, Haley-Johnson Z, Uk	J Neurosci	2026	0
TREM2-mediated microglial phagocytosis of inhibitory synapses contributes to pro [PMID:41965330]	Wang X, Zhou H, Zhai Y, Zhang Y, Cheng Y	Cell Death Discov	2026	0
Investigating the Potential of Gene Editing Technologies in Enhancing Stem Cell [PMID:41926312]	["Mehrabadi S"]	Current aging science	2026	0
TREM2 in neurodegeneration and diseases. [PMID:41792456]	["Abdulkhaliq A", "Alasiri G", "Kim B",	Molecular psychiatry	2026	0
Berbamine hydrochloride as a brain penetrant galectin 3 inhibitor in a model of [PMID:41772384]	["Siew J", "Lee C", "Chen H", "Lin H", "	Brain : a journal of neurology	2026	0
The microglial TREM2 receptor programs hippocampal development in a mouse model [PMID:41887542]	Ahmed S, Bowers C, Munoz-Martin J, Jamwa	Brain, behavior, and immunity	2026	0
Molecular mechanism of Alzheimer's disease using integrated multi-omics. [PMID:41907842]	Alhusaini M, Mussa BM, Ilce BY, Alhaj H,	Frontiers in aging neuroscienc	2026	0
Oligodendrocyte precursor cells-microglia crosstalk via BMP4 drives microglial n [PMID:41881962]	Baek S, Jang J, Yeo S, Jung HJ, Choe Y	Signal transduction and target	2026	0
Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ4 [PMID:41770935]	["Konstantoulea K", "Ramakers M", "Borri	Proceedings of the National Ac	2026	0

TREM2

Understanding Entity Pages

Summary

Wiki Pages (21)

sTREM2 (Soluble TREM2) - Biomarker

Personalized Treatment Plan — Atypical Parkinsonism (CBS/PSP)

Corticobasal Syndrome (CBS)

Novel Therapy Index

Parkinson's Disease

Sleep and Circadian Dysfunction in Alzheimer's Disease

Microglia CD8+ T Cell Recruitment -- Supplementary WW Content

Alzheimer's Disease Mechanism Index

nimodipine-als

Neuroresilience Mechanisms and Evidence

Therapeutics

Frontotemporal Dementia (FTD) Mechanistic Pathway

neuroinflammation

Alzheimer's Disease

nct07165106

Microglial Cells — Cell Type Hierarchy

NTF4 Protein

TREM2 Mechanism Hub

Neuroimmune Response in 4R-Tauopathies: Cross-Disease Comparison

Energy Metabolism Dysfunction Comparison Across Neurodegenerative Diseases

TREM2 Microglial Signaling Pathway in Neurodegeneration

Pathway Diagram

Outgoing (2035)

Incoming (1589)

Targeting Hypotheses (30)

Mentioning Analyses (30)

What is the temporal sequence of TREM2 signaling transition from protective to i

Why is TYROBP deficiency neuroprotective when TYROBP is an adapter for multiple

What are the specific molecular mechanisms by which peripheral monocytes cross t

Can biased TREM2 agonists selectively activate DAP12-SYK-PI3K without triggering

What are the optimal timing windows for TREM2 agonism vs antagonism across disea

Does SYK activation provide neuroprotection or exacerbate neuroinflammation in e

What are the optimal timing windows for TREM2 inhibition vs activation in Alzhei

What are the optimal temporal windows for TREM2 inhibition vs activation in Alzh

Do these mechanistic hypotheses from the SEA-AD Atlas bundle explain layer-speci

Do these mechanistic hypotheses explain layer-specific synaptic vulnerability in

Mechanistic validation of SEA-AD differential expression hypotheses: Complement

TREM2 Therapeutic Strategy Post-INVOKE-2

Epigenetic reprogramming in aging neurons

Neuroinflammation and microglial priming in early AD

Neuroinflammation and microglial priming in early Alzheimer's Disease

Neuroinflammation and microglial priming in early Alzheimer's Disease

Tau propagation mechanisms and therapeutic interception points

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

Immune atlas neuroinflammation analysis in neurodegeneration

Circuit-level neural dynamics in neurodegeneration

Tau propagation mechanisms and therapeutic interception points

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

TREM2 agonism vs antagonism in DAM microglia

Immune atlas neuroinflammation analysis in neurodegeneration

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

TREM2 Therapeutic Strategy Post-INVOKE-2

RNA binding protein dysregulation across ALS FTD and AD

Synaptic pruning by microglia in early AD

Neuroinflammation resolution mechanisms and pro-resolving mediators

Related Papers (20)