Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about TREM2 R47H Variant: 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.
A loss-of-function missense variant (rs75932628) in the TREM2 gene substituting arginine for histidine at position 47. This variant reduces TREM2 ligand binding by ~50%, impairs microglial activation and phagocytosis, and is the strongest genetic risk factor for late-onset Alzheimer's disease after APOE ε4 (OR ≈ 2-4). Carriers show reduced microglial clustering around amyloid plaques.
Ontology: RCV000033055
No AI portrait yet
| Name | TREM2 R47H |
| Key Genes/Proteins | APOE3 |
| Related Diseases | Alzheimer's disease |
| Linked Hypotheses | 4 hypotheses |
| Target | Relation | Type | Str |
|---|---|---|---|
| Alzheimer's disease | increases_risk_of | disease | 0.90 |
| PHAGOCYTOSIS | increases | process | 0.80 |
| APOE3 | affects | protein | 0.80 |
| TREM2-apoE3 interactions | affects | process | 0.80 |
| Source | Relation | Type | Str |
|---|---|---|---|
| No incoming edges | |||
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| TREM2 R47H Variant-Driven Metabolic Dysfunction as the Prima | 0.862 | neurodegeneration | Variant Annotation and Prioritization of |
| TREM2 R47H variant synergizes with APOE4 to collapse microgl | 0.681 | neuroscience | APOE4-driven lipid metabolism dysregulat |
| TREM2 R47H Metabolic Lock-in at Cholesterol Ester Accumulati | 0.672 | neuroimmunology | What is the temporal sequence of TREM2 s |
| TREM2 R47H Variant Correction — AAV-Mediated Rescue of Commo | 0.631 | Alzheimer's disease | TREM2 agonism vs antagonism in DAM micro |
Scientific analyses that reference this entity
No analyses mention this entity
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. Cost |
|---|---|---|---|---|---|---|---|
| NAD depletion effects on monocyte/macrophage differentiation | exploratory | Inflammatory bowel disease | 0.900 | 0.00 | Primary mouse and human monocy | proposed | N/A |
| FK866 treatment in DSS-induced colitis mouse model | validation | Inflammatory bowel disease (co | 0.900 | 0.00 | DSS-induced colitis mice | proposed | N/A |
| Unilateral ureteral obstruction model for hyperoside treatment | validation | chronic kidney disease | 0.900 | 0.00 | unilateral ureteral obstructio | proposed | N/A |
| Folic acid-induced nephropathy model for hyperoside renoprotection | validation | chronic kidney disease | 0.900 | 0.00 | folic acid-induced nephropathy | proposed | N/A |
| FK866 in azoxymethane/DSS colitis-associated cancer model | validation | Colitis-associated cancer | 0.850 | 0.00 | AOM/DSS-treated mice | proposed | N/A |
| FK866 mechanism validation in Rag1-/- mice | validation | Inflammatory bowel disease | 0.850 | 0.00 | Rag1-/- mice with DSS-induced | proposed | N/A |
| Hyperoside-ACAT1 direct binding interaction studies | exploratory | chronic kidney disease | 0.850 | 0.00 | in vitro protein-ligand bindin | proposed | N/A |
| CHI3L1 variant association with AD progression in human patients | exploratory | Alzheimer's disease | 0.850 | 0.00 | human patients | proposed | N/A |
| L-carnitine rescue experiments in metabolic pathway | exploratory | chronic kidney disease | 0.800 | 0.00 | ACAT1 knockdown with L-carniti | proposed | N/A |
| Acat1 knockdown functional validation experiment | exploratory | chronic kidney disease | 0.800 | 0.00 | Acat1 knockdown cells/tissues | proposed | N/A |
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease [PMID:41109213] | Pilat DJ, Le H, Prokopenko D, Lin CJ, Ei | Neuron | 2026 | 0 |
| Role of TREM2 in neuroinflammation. [PMID:41213496] | Abdulkhaliq AA, Alasiri G, Almoghrabi Y, | Exp Neurol | 2026 | 0 |
| Synergistic potential of TREM2 agonists and exercise training in Alzheimer's dis [PMID:41494649] | Zhang J, St Pierre Schneider B, Muguerza | Am J Physiol Endocrinol Metab | 2026 | 0 |
| Armored macrophage-targeted CAR-T cells reset and reprogram the tumor microenvir [PMID:41576929] | Mateus-Tique J, Lakshmi A, Singh B, Iyer | Cancer Cell | 2026 | 0 |
| Peripheral cancer attenuates amyloid pathology in Alzheimer's disease via cystat [PMID:41576952] | Li X, Tang X, Zeng J, Duan L, Hou Z et a | Cell | 2026 | 0 |
| TREM2 expression level is critical for microglial state, metabolic capacity and [PMID:41580393] | Feiten AF, Dahm K, Schlepckow K, van Len | Nat Commun | 2026 | 0 |
| Large-scale single-cell analysis and in silico perturbation reveal dynamic evolu [PMID:41617928] | Xia P, Shuang S, Fu D, Liu L, Yang D et | NPJ Precis Oncol | 2026 | 0 |
| Dissecting genetic and immune drivers of heterogeneous responses to neoadjuvant [PMID:41720086] | Zhao Q, Huang R, Wang C, Hu J, Nie R et | Cancer Cell | 2026 | 0 |
| TREM2 in neurodegeneration and diseases. [PMID:41792456] | ["Abdulkhaliq A", "Alasiri G", "Kim B", | Molecular psychiatry | 2026 | 0 |
| Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation. [PMID:41745721] | Aranda-Abreu GE, Rojas-Durán F, Hernánde | Neurology international | 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 |
| Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] | ["Chen Kai", "Li Fuyao", "Zhang Shuwen", | Journal of neuroinflammation | 2025 | 0 |
| Viral and non-viral cellular therapies for neurodegeneration. [PMID:41585268] | ["Srivastav Jyotsna", "Sharma Sachin"] | Frontiers in medicine | 2025 | 0 |
| Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] | ["Chen Kai", "Li Fuyao", "Zhang Shuwen", | Journal of neuroinflammation | 2025 | 0 |
| Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554] | Marogianni C, Sokratous M, Dardiotis E, | International journal of molec | 2020 | 0 |
| Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554] | Marogianni C, Sokratous M, Dardiotis E, | International journal of molec | 2020 | 0 |
| Multiple Sclerosis Pathology. [PMID:29358320] | Lassmann H | Cold Spring Harbor perspective | 2018 | 0 |
Multi-agent debates referencing this entity
No debates reference this entity
Hypotheses and analyses mentioning TREM2 R47H Variant in their description or question text
No additional research found