TREM2

Summary

TREM2 (triggering receptor expressed on myeloid cells 2, HGNC:17761) is a protein-coding gene on chromosome 6p21.1, encoding Triggering receptor expressed on myeloid cells 2 (Q9NZC2). Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding.

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.

Source: NCBI Gene 54209 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 194 total — 11 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 160
• Druggable target: yes
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_018965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17761
Approved symbol	TREM2
Name	triggering receptor expressed on myeloid cells 2
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	TREM-2, Trem2a, Trem2b, Trem2c
Ensembl gene	ENSG00000095970
Ensembl biotype	protein_coding
OMIM	605086
Entrez	54209

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000338469, ENST00000373113, ENST00000373122, ENST00000880536

RefSeq mRNA: 2 — MANE Select: NM_018965 NM_001271821, NM_018965

CCDS: CCDS4852, CCDS64422

Canonical transcript exons

ENST00000373113 — 5 exons

Exon	Start	End
ENSE00000619020	41161263	41161613
ENSE00000750553	41159792	41159882
ENSE00000849874	41158873	41159066
ENSE00001922142	41163043	41163116
ENSE00003592646	41158508	41158780

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 92.42.

FANTOM5 (CAGE): breadth broad, TPM avg 10.5118 / max 727.6496, expressed in 330 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73527	8.0166	299
73530	1.8012	242
73529	0.5504	160
73528	0.1435	71

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	92.42	gold quality
spinal cord	UBERON:0002240	91.22	gold quality
amniotic fluid	UBERON:0000173	85.54	gold quality
olfactory bulb	UBERON:0002264	84.03	gold quality
inferior vagus X ganglion	UBERON:0005363	83.82	gold quality
substantia nigra	UBERON:0002038	83.46	gold quality
midbrain	UBERON:0001891	82.38	gold quality
cranial nerve II	UBERON:0000941	81.56	gold quality
right coronary artery	UBERON:0001625	80.90	gold quality
gall bladder	UBERON:0002110	80.72	gold quality
left adrenal gland	UBERON:0001234	79.82	gold quality
subthalamic nucleus	UBERON:0001906	79.61	gold quality
upper lobe of left lung	UBERON:0008952	79.12	gold quality
left adrenal gland cortex	UBERON:0035825	79.12	gold quality
prefrontal cortex	UBERON:0000451	78.36	gold quality
upper lobe of lung	UBERON:0008948	78.26	gold quality
amygdala	UBERON:0001876	77.73	gold quality
right adrenal gland	UBERON:0001233	77.36	gold quality
adrenal cortex	UBERON:0001235	77.35	gold quality
right uterine tube	UBERON:0001302	77.04	gold quality
hypothalamus	UBERON:0001898	76.84	gold quality
type B pancreatic cell	CL:0000169	76.81	gold quality
decidua	UBERON:0002450	76.69	silver quality
caudate nucleus	UBERON:0001873	76.59	gold quality
right lung	UBERON:0002167	76.36	gold quality
descending thoracic aorta	UBERON:0002345	76.27	gold quality
right adrenal gland cortex	UBERON:0035827	76.24	gold quality
putamen	UBERON:0001874	76.00	gold quality
Ammon’s horn	UBERON:0001954	75.88	gold quality
tibial nerve	UBERON:0001323	75.85	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	74.78
E-GEOD-84465	yes	40.32
E-MTAB-7316	yes	15.43
E-CURD-112	yes	13.57
E-ANND-3	yes	7.35
E-GEOD-137537	yes	5.41

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
APOC1	Activation
APOE	Activation
ARG1	Unknown
CCL3	Unknown
CST7	Activation
FABP5	Activation
IL1A	Activation
IL1B	Activation
IL6	Unknown
LIPA	Activation
TNF	Activation

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

13 targeting TREM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-2278	97.30	66.19	1130

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in two genes encoding different subunits of a receptor signaling complex (TYROBP and TREM2) result in an identical disease phenotype (PMID:12080485)
• The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes TREM2. (PMID:12645956)
• Nasu-Hakola disease with a novel genetic mutations in the TREM2 gene (PMID:12754369)
• results demonstrate a critical role for TREM-2 in the differentiation of mononuclear myeloid precursors into functional multinucleated osteoclasts (PMID:12913093)
• These results indicate an important role for DAP12-TREM2 signaling complex in the differentiation and function of osteoclasts. (PMID:12925681)
• Two healthy subjects heterozygous for one mutated TREM2 allele showed a deficit of visuospatial memory associated with hypoperfusion in the basal ganglia, whereas the homozygotes for the wild-type allele of TREM2 did not show any abnormalities. (PMID:15966270)
• Mutation in Nasu-Hakola disease. (PMID:16505336)
• Transcript analysis of DCs of PLOSL patients show that TREM2 deficient cells differentiated into DCs and responded to pathogenic stimuli. However, the DCs showed morphological differences due to defects in the actin filaments. (PMID:17530208)
• Mutations in TREM2 lead to pure early-onset dementia without bone cysts (PMID:18546367)
• TREM2 is induced and expressed in microglia associated with amyloid plaques where it may impact on their differentiation state and function in aged APP23 transgenic mice, an animal model of Alzheimer’s disease. (PMID:18551625)
• the DAP12-TREM2 complex unlikely has a role in genetic susceptibility of multiple sclerosis (PMID:19019460)
• TREM-2 can function as a pattern-recognition receptor in the induction of the innate immune response to gonococci. (PMID:19079182)
• decreased percentages of TREM-2 positive monocytes in patients with multiple sclerosis (PMID:19230638)
• Treatment with Hsp60 was found to stimulate the best known TREM2-dependent process, phagocytosis, however, only in the microglial N9 cells rich in the receptor. (PMID:19457124)
• These findings indicate that DAP12, possibly through association with TREM2, contributes to alveolar macrophage chemotaxis and recruitment to the lung and may mediate macrophage accumulation in lung diseases such as emphysema. (PMID:20421649)
• TREM2 expression correlates positively with amyloid phagocytosis in a transgenic model of amyloid pathology. (PMID:20640189)
• This is the first report of a Japanese Nasu-Hakola disease family caused by a splicing mutation of TREM2 that induces both neuroinflammation and neurodegeneration. (PMID:21834902)
• we have identified a common TREM2 variant associated with CRP in United States minority populations. (PMID:22939635)
• Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer’s disease. (PMID:23150908)
• Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer’s disease. (PMID:23150934)
• An association is found between rs75932628-T variant of TREM2 and early-onset Alzheimer’s disease. (PMID:23380991)
• A positive replication study in a Spanish population confirms that TREM2 rs75932628-T is associated with risk for Alzheimer’s disease. (PMID:23391427)
• REVIEW: the recent epidemiological findings of TREM2 that related with late-onset AD and speculate the possible roles of TREM2 in progression of this disease (PMID:23407992)
• TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. (PMID:23533697)
• Mutation in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease. (PMID:23582655)
• TREM-2 plays an important role in the host defense response to sepsis by enhancing bacterial clearance. (PMID:23721075)
• Its mutations are rare in a French cohort of patients with frontotemporal dementia. (PMID:23759145)
• Our results suggest that the TREM2 p.R47H substitution is a risk factor for frontotemporal dementia and Parkinson’s disease (PMID:23800361)
• R47H variant of TREM2 is an Alzheimer’s disease risk factor. (PMID:23855982)
• It is significantly enriched for genes genetically implicated in Alzheimer’s disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia. (PMID:23855984)
• Its homozygous mutations cause frontotemporal dementia. (review) (PMID:23870839)
• Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in Alzheimer disease patients. This study observed a significant correlation between TREM2 expressions and MMSE score. (PMID:24002183)
• the accumulated TREM2 CTF thereby might limit the interaction of DAP12 with the functional full-length receptor, resulting in decreased DAP12 phosphorylation and impaired metabolism of phosphatidylinositol 4,5-bisphosphate. (PMID:24078628)
• TREM2 variants may play a role in neurodegenerative diseases in general. (PMID:24119542)
• The combined analysis confirmed the association of the R47H variant of TREM2 with Parkinson’s disease. (PMID:24131187)
• Heterozygous TREM2 mutations modulate the risk of FTD in addition to increasing susceptibility to AD. (PMID:24139279)
• Mutations in exon2 of TREM2 are unlikely to play a key role in the susceptibility of LOAD in the northern Han Chinese population. (PMID:24184202)
• propose that TREM2 is a potential therapeutic target for stopping ordelaying progression of AD (PMID:24355566)
• Its association with cognitive performance has been known. (PMID:24378087)
• TREM2 p.R47H variant signaling pathway is increased in spinal cord samples from amyotrophic lateral sclerosis patients; its experssion negatively correlates with survival in transgenic mice. (PMID:24535663)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trem2	ENSMUSG00000023992
rattus_norvegicus	Trem2	ENSRNOG00000013578

Paralogs (13): TMIGD3 (ENSG00000121933), CD300LG (ENSG00000161649), TREML1 (ENSG00000161911), FCMR (ENSG00000162894), PIGR (ENSG00000162896), FCAMR (ENSG00000162897), CD300C (ENSG00000167850), CD300A (ENSG00000167851), CD300LB (ENSG00000178789), CD300LF (ENSG00000186074), CD300E (ENSG00000186407), CD300LD (ENSG00000204345), CD300H (ENSG00000284690)

Protein

Protein identifiers

Triggering receptor expressed on myeloid cells 2 — Q9NZC2 (reviewed: Q9NZC2)

Alternative names: Triggering receptor expressed on monocytes 2

All UniProt accessions (2): Q9NZC2, Q5TCX1

UniProt curated annotations — full annotation on UniProt →

Function. Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding. 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. 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. Binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and sphingomyelin. Regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade. Required for microglial phagocytosis of apoptotic neurons. 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. Triggers activation of the immune responses in macrophages and dendritic cells. Mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages. In dendritic cells, receptor of SEMA6D with PLEXNA1 as coreceptor and mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival. Involved in the positive regulation of osteoclast differentiation.

Subunit / interactions. Monomer. After ectodomain shedding, the extracellular domain oligomerizes, which is enhanced and stabilized by binding of phosphatidylserine. Interacts with TYROBP/DAP12. Interaction with TYROBP is required for stabilization of the TREM2 C-terminal fragment (TREM2-CTF) which is produced by proteolytic processing. Interacts with PLXNA1 (via TIG domains); the interaction mediates SEMA6D binding and signaling through TYROBP.

Subcellular location. Cell membrane Secreted Secreted.

Tissue specificity. Expressed in the brain, specifically in microglia and in the fusiform gyrus (at protein level). Expressed on macrophages and dendritic cells but not on granulocytes or monocytes. In the CNS strongest expression seen in the basal ganglia, corpus callosum, medulla oblongata and spinal cord.

Post-translational modifications. Undergoes ectodomain shedding through proteolytic cleavage by ADAM10 and ADAM17 to produce a transmembrane segment, the TREM2 C-terminal fragment (TREM2-CTF), which is subsequently cleaved by gamma-secretase.

Disease relevance. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (PLOSL2) [MIM:618193] An autosomal recessive disease characterized by presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years. The disease is caused by variants affecting the gene represented in this entry. Alzheimer disease 17 (AD17) [MIM:615080] A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NZC2-1	1	yes
Q9NZC2-2	2, TREM-2V
Q9NZC2-3	3

RefSeq proteins (2): NP_001258750, NP_061838* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR052314	Immune_rcpt_domain	Family

Pfam: PF07686

UniProt features (79 total): sequence variant 35, strand 9, mutagenesis site 7, helix 7, turn 4, binding site 4, glycosylation site 2, disulfide bond 2, splice variant 2, topological domain 2, signal peptide 1, chain 1, site 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
6XDS	X-RAY DIFFRACTION	1.47
5UD8	X-RAY DIFFRACTION	1.8
9PWN	X-RAY DIFFRACTION	1.8
8T51	X-RAY DIFFRACTION	1.9
8T59	X-RAY DIFFRACTION	2
6B8O	X-RAY DIFFRACTION	2.2
5UD7	X-RAY DIFFRACTION	2.2
6Y6C	X-RAY DIFFRACTION	2.26
6YMQ	X-RAY DIFFRACTION	3.07
5ELI	X-RAY DIFFRACTION	3.1
6YYE	X-RAY DIFFRACTION	3.36
9PX5	X-RAY DIFFRACTION	3.7
6Z0G	SOLUTION NMR
6Z0H	SOLUTION NMR
6Z0I	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZC2-F1	76.85	0.50

Antibody-complex structures (SAbDab): 7 — 6Y6C, 6YMQ, 6YYE, 8T51, 8T59, 9PWN, 9PX5

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 157–158 (cleavage of ectodomain)

Ligand- & substrate-binding residues (4): 67; 68; 77; 88

Disulfide bonds (2): 36–110, 51–60

Glycosylation sites (2): 20, 79

Mutagenesis-validated functional residues (7):

Position	Phenotype
20	loss of glycosylation.
36	loss of proteolytic cleavage by adam10 and ectodomain shedding. decreases protein maturation and cell membrane localizat
48	loss of ldl, clu and apoe binding.
60	loss of proteolytic cleavage by adam10 and ectodomain shedding. decreases protein maturation and cell membrane localizat
68	no effect on cell membrane localization.
76	decreases binding to thp-1 cells.
77	decreases binding to thp-1 cells.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127	DAP12 interactions
R-HSA-2424491	DAP12 signaling
R-HSA-416700	Other semaphorin interactions

MSigDB gene sets: 878 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_DENDRITIC_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS

GO Biological Process (114): microglial cell activation (GO:0001774), microglial cell activation involved in immune response (GO:0002282), T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:0002291), positive regulation of antigen processing and presentation of peptide antigen via MHC class II (GO:0002588), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), response to ischemia (GO:0002931), phagocytosis, recognition (GO:0006910), phagocytosis, engulfment (GO:0006911), humoral immune response (GO:0006959), signal transduction (GO:0007165), memory (GO:0007613), regulation of gene expression (GO:0010468), negative regulation of autophagy (GO:0010507), positive regulation of gene expression (GO:0010628), positive regulation of cholesterol efflux (GO:0010875), negative regulation of cholesterol storage (GO:0010887), negative regulation of triglyceride storage (GO:0010891), positive regulation of high-density lipoprotein particle clearance (GO:0010983), regulation of lipid metabolic process (GO:0019216), osteoclast differentiation (GO:0030316), regulation of TOR signaling (GO:0032006), positive regulation of TOR signaling (GO:0032008), detection of lipopolysaccharide (GO:0032497), detection of peptidoglycan (GO:0032499), regulation of interleukin-6 production (GO:0032675), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of interleukin-10 production (GO:0032733), negative regulation of toll-like receptor 2 signaling pathway (GO:0034136), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), regulation of toll-like receptor 6 signaling pathway (GO:0034151), positive regulation of macrophage fusion (GO:0034241), negative regulation of glial cell apoptotic process (GO:0034351), social behavior (GO:0035176), CXCL12-activated CXCR4 signaling pathway (GO:0038160), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of potassium ion transport (GO:0043268), apoptotic cell clearance (GO:0043277), regulation of innate immune response (GO:0045088), positive regulation of osteoclast differentiation (GO:0045672)

GO Molecular Function (26): lipopolysaccharide binding (GO:0001530), amyloid-beta binding (GO:0001540), phosphatidylserine binding (GO:0001786), transmembrane signaling receptor activity (GO:0004888), phospholipid binding (GO:0005543), beta-catenin binding (GO:0008013), high-density lipoprotein particle binding (GO:0008035), lipid binding (GO:0008289), phosphatidylethanolamine binding (GO:0008429), semaphorin receptor activity (GO:0017154), kinase activator activity (GO:0019209), low-density lipoprotein particle binding (GO:0030169), semaphorin receptor binding (GO:0030215), apolipoprotein binding (GO:0034185), apolipoprotein A-I binding (GO:0034186), very-low-density lipoprotein particle binding (GO:0034189), signaling receptor activity (GO:0038023), peptidoglycan binding (GO:0042834), protein-containing complex binding (GO:0044877), lipoteichoic acid binding (GO:0070891), lipoprotein particle binding (GO:0071813), scaffold protein binding (GO:0097110), sulfatide binding (GO:0120146), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515), carbohydrate derivative binding (GO:0097367)

GO Cellular Component (5): semaphorin receptor complex (GO:0002116), extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), plasma membrane raft (GO:0044853)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Adaptive Immune System	1
Innate Immune System	1
DAP12 interactions	1
Semaphorin interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
lipoprotein particle binding	3
immune response	2
phagocytosis	2
gene expression	2
negative regulation of lipid storage	2
lipid binding	2
carbohydrate derivative binding	2
phospholipid binding	2
binding	2
cellular anatomical structure	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
microglial cell activation	1
macrophage activation involved in immune response	1
T cell activation involved in immune response	1
antigen processing and presentation of peptide antigen via MHC class II	1
positive regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1
positive regulation of antigen processing and presentation of peptide antigen	1
regulation of antigen processing and presentation of peptide antigen via MHC class II	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
response to stress	1
cell recognition	1
cargo receptor activity	1
plasma membrane invagination	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
learning or memory	1
regulation of macromolecule biosynthetic process	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of gene expression	1

Protein interactions and networks

STRING

2320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TREM2	TYROBP	O43914	999
TREM2	APOE	P02649	994
TREM2	FCER1G	P30273	990
TREM2	CLU	P10909	980
TREM2	TREM1	Q9NP99	979
TREM2	CD33	P20138	953
TREM2	TREML2	Q5T2D2	918
TREM2	TREML1	Q86YW5	880
TREM2	P2RY12	Q9H244	867
TREM2	APP	P05067	853
TREM2	SYK	P43405	813
TREM2	LGALS3	P17931	811
TREM2	TMEM119	Q4V9L6	810
TREM2	CSF1R	P07333	805
TREM2	PSEN1	P49768	801

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PSEN1	NCSTN	psi-mi:“MI:0914”(association)	0.790
TREM2	TYROBP	psi-mi:“MI:0915”(physical association)	0.670
TREM2	TYROBP	psi-mi:“MI:0403”(colocalization)	0.670
APP	TREM2	psi-mi:“MI:0915”(physical association)	0.610
TREM2	APP	psi-mi:“MI:0407”(direct interaction)	0.610
TREM2	PSEN1	psi-mi:“MI:0915”(physical association)	0.600
TREM2	PSEN1	psi-mi:“MI:0403”(colocalization)	0.600
APOE	TREM2	psi-mi:“MI:0915”(physical association)	0.600
TREM2	APOE	psi-mi:“MI:0407”(direct interaction)	0.600
TREM2	APOE	psi-mi:“MI:0915”(physical association)	0.600
TREM2	APP	psi-mi:“MI:0407”(direct interaction)	0.440
TNFRSF12A	TREM2	psi-mi:“MI:0915”(physical association)	0.400
TREM2	NUCB2	psi-mi:“MI:0914”(association)	0.350
TREM2	HMG20A	psi-mi:“MI:0915”(physical association)	0.000
TREM2	SNRNP70	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): APOA1 (Reconstituted Complex), GH1 (Reconstituted Complex), NRN1L (Reconstituted Complex), SCGB2A2 (Reconstituted Complex), UNC5B (Reconstituted Complex), APOA2 (Reconstituted Complex), APOB (Reconstituted Complex), CLU (Reconstituted Complex), APOE (Reconstituted Complex), ATP6V0A2 (Affinity Capture-MS), NUCB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

Diamond homologs: A1KXC4, A2A7V7, A2TGX5, A5D7B2, O60667, O70570, O95944, P01832, P01833, P0DUB1, P15083, P81265, Q08708, Q1ERP8, Q29244, Q2TB54, Q3U497, Q496F6, Q566E6, Q5M871, Q5R770, Q6SJQ7, Q6UXG3, Q7TSN2, Q8K249, Q8TDQ1, Q8VCH2, Q8WWV6, Q9NZC2, Q9UGN4, A0A0K2S4Q6, Q3LRV9, Q6SJQ0, Q6UXN2, Q8K558, A8K4G0, G3X8R9, P0DMS9, Q6SJQ5, Q6UXZ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

194 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	10
Uncertain significance	77
Likely benign	63
Benign	3

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1178350	NM_018965.4(TREM2):c.594G>A (p.Trp198Ter)	Pathogenic
1676016	NM_018965.4(TREM2):c.199del (p.His67fs)	Pathogenic
192241	NM_018965.4(TREM2):c.113A>G (p.Tyr38Cys)	Pathogenic
2426502	NC_000006.11:g.(?41126341)(41130820_?)del	Pathogenic
2583155	NM_018965.4(TREM2):c.40+1G>A	Pathogenic
2693499	NM_018965.4(TREM2):c.256_265del (p.Asp86fs)	Pathogenic
3012919	NM_018965.4(TREM2):c.368del (p.Lys123fs)	Pathogenic
4687831	NM_018965.4(TREM2):c.491T>A (p.Leu164Ter)	Pathogenic
5219	NM_018965.4(TREM2):c.97C>T (p.Gln33Ter)	Pathogenic
56722	NM_018965.4(TREM2):c.313del (p.Ala105fs)	Pathogenic
56724	NM_018965.4(TREM2):c.40G>T (p.Glu14Ter)	Pathogenic
1473898	NM_018965.4(TREM2):c.483-2A>C	Likely pathogenic
1498893	NM_018965.4(TREM2):c.483-1G>A	Likely pathogenic
2715444	NM_018965.4(TREM2):c.392-2A>T	Likely pathogenic
3341881	NM_018965.4(TREM2):c.257A>T (p.Asp86Val)	Likely pathogenic
3381007	NM_018965.4(TREM2):c.114T>G (p.Tyr38Ter)	Likely pathogenic
3391393	NM_018965.4(TREM2):c.41-1G>C	Likely pathogenic
4086449	NM_018965.4(TREM2):c.428del (p.Phe143fs)	Likely pathogenic
5213	NM_018965.4(TREM2):c.233G>A (p.Trp78Ter)	Likely pathogenic
5217	NM_018965.4(TREM2):c.132G>A (p.Trp44Ter)	Likely pathogenic
56721	NM_018965.4(TREM2):c.269del (p.Gly90fs)	Likely pathogenic

SpliceAI

703 predictions. Top by Δscore:

Variant	Effect	Δscore
6:41159068:T:C	acceptor_gain	1.0000
6:41159786:CTGTA:C	donor_loss	1.0000
6:41159787:TGTA:T	donor_loss	1.0000
6:41159788:GTAC:G	donor_loss	1.0000
6:41159789:TACCT:T	donor_loss	1.0000
6:41159790:A:T	donor_loss	1.0000
6:41159791:CCTG:C	donor_loss	1.0000
6:41159883:C:CC	acceptor_gain	1.0000
6:41163037:TCCTA:T	donor_loss	1.0000
6:41163038:CCTAC:C	donor_loss	1.0000
6:41163039:CTA:C	donor_loss	1.0000
6:41163040:TACCT:T	donor_loss	1.0000
6:41163041:A:T	donor_loss	1.0000
6:41159066:CCT:C	acceptor_gain	0.9900
6:41159068:T:TC	acceptor_gain	0.9900
6:41160063:T:TA	donor_gain	0.9900
6:41161609:CAGCT:C	acceptor_gain	0.9900
6:41158778:GCCCT:G	acceptor_loss	0.9800
6:41158780:CCTGC:C	acceptor_loss	0.9800
6:41158781:C:CC	acceptor_gain	0.9800
6:41158781:C:G	acceptor_loss	0.9800
6:41158782:T:C	acceptor_loss	0.9800
6:41159012:C:CT	acceptor_gain	0.9800
6:41159013:A:T	acceptor_gain	0.9800
6:41159064:CTC:C	acceptor_gain	0.9800
6:41159067:C:CC	acceptor_gain	0.9800
6:41159880:GGTCT:G	acceptor_loss	0.9800
6:41159881:GT:G	acceptor_gain	0.9800
6:41159881:GTCT:G	acceptor_loss	0.9800
6:41159882:TC:T	acceptor_loss	0.9800

AlphaMissense

1494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:41161504:C:A	W50C	0.993
6:41161504:C:G	W50C	0.993
6:41161510:C:A	K48N	0.991
6:41161510:C:G	K48N	0.991
6:41161506:A:G	W50R	0.990
6:41161506:A:T	W50R	0.990
6:41161325:C:G	C110S	0.989
6:41161326:A:T	C110S	0.989
6:41161331:T:C	Y108C	0.988
6:41161332:A:C	Y108D	0.986
6:41161326:A:G	C110R	0.981
6:41161502:C:G	C51S	0.980
6:41161503:A:T	C51S	0.980
6:41161403:A:T	I84N	0.977
6:41161370:A:T	I95N	0.976
6:41161547:C:G	C36S	0.973
6:41161548:A:T	C36S	0.973
6:41161376:A:G	L93P	0.972
6:41161403:A:G	I84T	0.972
6:41161331:T:G	Y108S	0.969
6:41161370:A:C	I95S	0.969
6:41161548:A:G	C36R	0.969
6:41161332:A:T	Y108N	0.968
6:41161324:G:C	C110W	0.964
6:41161509:C:G	A49P	0.964
6:41161370:A:G	I95T	0.963
6:41161512:T:C	K48E	0.961
6:41161547:C:T	C36Y	0.961
6:41161503:A:G	C51R	0.960
6:41161511:T:G	K48T	0.959

dbSNP variants (sampled 300 via entrez): RS1000218712 (6:41159284 C>T), RS1000412848 (6:41164664 A>T), RS1000739474 (6:41158063 T>A), RS1001269749 (6:41163254 G>A,C), RS1001372793 (6:41161036 G>A), RS1002057411 (6:41160861 T>C), RS1002087034 (6:41160670 C>A,T), RS1003725484 (6:41162270 G>T), RS1003756223 (6:41161980 T>A), RS1004875471 (6:41158492 A>C,G), RS1004928526 (6:41163945 T>C), RS1005368749 (6:41158701 G>A), RS1005388986 (6:41164263 C>T), RS1007830203 (6:41160199 C>T), RS1007861089 (6:41160027 G>C)

Disease associations

OMIM: gene MIM:605086 | disease phenotypes: MIM:618193, MIM:221770

GenCC curated gene-disease

Disease	Classification	Inheritance
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2	Strong	Autosomal recessive
Alzheimer disease 17	Strong	Autosomal recessive
polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly	Supportive	Autosomal recessive

Mondo (5): frontotemporal dementia (MONDO:0017276), polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (MONDO:0020750), polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (MONDO:0020749), polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly (MONDO:0009092), Alzheimer disease 17 (MONDO:0014036)

Orphanet (2): Frontotemporal dementia (Orphanet:282), Nasu-Hakola disease (Orphanet:2770)

HPO phenotypes

160 total (30 of 160 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000217	Xerostomia
HP:0000238	Hydrocephalus
HP:0000474	Thickened nuchal skin fold
HP:0000504	Abnormality of vision
HP:0000657	Oculomotor apraxia
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000710	Hyperorality
HP:0000711	Restlessness
HP:0000712	Emotional lability
HP:0000713	Agitation
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000719	Inappropriate behavior
HP:0000723	Restrictive behavior
HP:0000726	Dementia
HP:0000727	Frontal lobe dementia
HP:0000733	Motor stereotypy
HP:0000734	Disinhibition
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000751	Personality changes
HP:0000757	Lack of insight
HP:0000938	Osteopenia
HP:0001155	Abnormality of the hand
HP:0001249	Intellectual disability

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001650_7	C-reactive protein	1.000000e-10
GCST001743_1	Alzheimer’s disease	2.000000e-12
GCST005549_10	Alzheimer’s disease (late onset)	5.000000e-24
GCST005549_7	Alzheimer’s disease (late onset)	2.000000e-14
GCST005936_5	Supraventricular ectopy	1.000000e-06
GCST006585_1726	Blood protein levels	3.000000e-10
GCST007320_57	Alzheimer’s disease or family history of Alzheimer’s disease	1.000000e-16
GCST007320_91	Alzheimer’s disease or family history of Alzheimer’s disease	3.000000e-08
GCST007321_31	Family history of Alzheimer’s disease	2.000000e-16

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0009277	supraventricular ectopy
EFO:0009268	family history of Alzheimer’s disease

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D057180	Frontotemporal Dementia	C10.228.140.380.266.299; C10.574.950.300.299; C18.452.845.800.300.299; F03.615.400.380.299

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196124 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Immunoglobulin like domain containing proteins

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
T2M-010	Agonist	6.08	pKd
TREM2 agonist 4i	Agonist	4.72	pKd
TREM2 agonist C1	Agonist	4.15	pKd

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	EC50	1	nM	CHEMBL6172797
8.70	EC50	2	nM	CHEMBL6165036
8.70	EC50	2	nM	CHEMBL6166127
8.52	EC50	3	nM	CHEMBL6174051
8.40	EC50	4	nM	CHEMBL6165261
8.30	EC50	5	nM	CHEMBL6166220

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	5
Aflatoxin B1	affects expression, increases expression	5
aristolochic acid I	increases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Cisplatin	increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Estradiol	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6141350	Binding	Agonist activity at human TREM2 expressed in HEK cells co-expressing human DAP12 assessed as increase in Syk phosphorylation incubated for 30 mins by AlphaLISA assay	Novel Pyrido[3,4-d]pyrimidin-4-one and Pyrimido[5,4-d]pyrimidin-4-one Derivatives as TREM2 Agonists for Treating Parkinson’s Disease. — ACS Med Chem Lett

Cellosaurus cell lines

37 cell lines: 33 induced pluripotent stem cell, 2 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AB84	Lymph2-AD2-iPS	Induced pluripotent stem cell	Male
CVCL_B1AM	Abcam THP-1 TREM2 KO	Cancer cell line	Male
CVCL_C6RB	LBi016-A	Induced pluripotent stem cell	Female
CVCL_C6RC	LBi016-B	Induced pluripotent stem cell	Female
CVCL_C6RD	LBi017-A	Induced pluripotent stem cell	Female
CVCL_C6RE	LBi017-B	Induced pluripotent stem cell	Female
CVCL_C6RF	LBi018-A	Induced pluripotent stem cell	Female
CVCL_C6RG	LBi018-B	Induced pluripotent stem cell	Female
CVCL_C6RH	LBi019-A	Induced pluripotent stem cell	Male
CVCL_C6RI	LBi019-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

146 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00376051	PHASE4	COMPLETED	Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT06093126	PHASE4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT00594737	PHASE3	COMPLETED	Open Label Pilot Study of the Effects of Memantine on FDG-PET in Frontotemporal Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT04374136	PHASE3	TERMINATED	A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)
NCT00416169	PHASE2	COMPLETED	A Pilot Study to Explore the Safety and Tolerability of Galantamine HBr in the Treatment of Pick Complex/Frontotemporal Dementia
NCT01890343	PHASE2	COMPLETED	Imaging Characteristics of Florbetapir 18F in Patients With Frontotemporal Dementia, Alzheimer’s Disease and Normal Controls.
NCT01937013	PHASE2	COMPLETED	Impact of Emotional Mimicry and Oxytocin on Frontotemporal Dementia
NCT02676843	PHASE2	COMPLETED	Tau PET Imaging With 18F-AV-1451 in Subjects With MAPT Mutations
NCT02862210	PHASE2	COMPLETED	Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
NCT03260920	PHASE2	UNKNOWN	Intranasal Oxytocin for Frontotemporal Dementia
NCT03987295	PHASE2	COMPLETED	A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)
NCT04220021	PHASE2	ACTIVE_NOT_RECRUITING	Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD
NCT04489017	PHASE2	COMPLETED	Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial
NCT04937452	PHASE2	COMPLETED	Dopaminergic Therapy for Frontotemporal Dementia Patients
NCT04993755	PHASE2	COMPLETED	A Phase 2a Study of TPN-101 in Patients With C9ORF72 ALS/FTD
NCT05742698	PHASE2	RECRUITING	Nabilone for Agitation in Frontotemporal Dementia
NCT06604520	PHASE2	RECRUITING	Vortioxetine for the Treatment of Mood and Cognitive Symptoms in Frontotemporal Dementia
NCT07154485	PHASE2	NOT_YET_RECRUITING	Investigator Initiated Study for the Safety and Efficacy in Frontotemporal Dementia
NCT01386333	PHASE1	COMPLETED	Safety Study of Intranasal Oxytocin in Frontotemporal Dementia
NCT03040713	PHASE1	COMPLETED	Flortaucipir PET Imaging in Subjects With FTD
NCT03636204	PHASE1	COMPLETED	A First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation
NCT05315661	PHASE1	ACTIVE_NOT_RECRUITING	The Safety and The Efficacy Evaluation of ET-STEM in Patients With Frontotemporal Dementia
NCT06705192	PHASE1	COMPLETED	Study in Asymptomatic GRN-FTD Patients to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VES001
NCT04100889	Not specified	WITHDRAWN	A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Alzheimer’s Disease
NCT05637801	Not specified	ACTIVE_NOT_RECRUITING	A Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (HOPE Study)
NCT04408625	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
NCT04747431	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes
NCT04931862	PHASE1/PHASE2	TERMINATED	Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)
NCT05262023	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN)
NCT05374278	PHASE1/PHASE2	RECRUITING	First-in-Human Evaluation of an Astrocytic Glutamate Transporter (EAAT2) PET Tracer in Dementia
NCT05683860	PHASE1/PHASE2	TERMINATED	Open-label Extension (OLE) Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) and/or Frontotemporal Dementia (FTD)
NCT06064890	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety and Effect of AVB-101, a Gene Therapy Product, in Subjects With a Genetic Sub-type of Frontotemporal Dementia (FTD-GRN)
NCT03510572	EARLY_PHASE1	COMPLETED	Evaluation of [18F]PI-2620 as a Potential Positron Emission Computed Tomography Radioligand for Imaging Tau Protein in the Brain
NCT03625128	EARLY_PHASE1	COMPLETED	18F-PM-PBB3 PET Study in Tauopathy Including Alzheimer’s Disease, Other Dementias and Normal Controls
NCT06891716	EARLY_PHASE1	RECRUITING	[18F]ACI-19626 PET in TDP-43 Proteinopathies
NCT00159198	Not specified	TERMINATED	Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
NCT00938665	Not specified	COMPLETED	Evaluation of a Handheld Event Related Potential (ERP)/Quantitative Electroencephalography (qEEG) System (COGNISION™) as a Useful Cognitive Biomarker for Alzheimer’s Disease.
NCT01002300	Not specified	COMPLETED	Oxytocin and Social Cognition in Frontotemporal Dementia