gene

P2RY12

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about P2RY12: 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.

641Connections

19Hypotheses

7Analyses

50Outgoing

50Incoming

11Experiments

9Debates

Summary

P2RY12 is a gene implicated in neurodegeneration research. Key relationships include: inhibits, activates, co discussed. Associated with AD, ALS, AMI. Connected to 208 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	P2RY12
Full Name	Purinergic Receptor P2Y12
Chromosome	3q25.1-q25.2
Protein Type	Gpcr
Target Class	Gpcr
Function	P2RY12 is a Gi/o protein-coupled receptor for ADP that plays a critical role in microglial surveillance and neuroimmune responses in the brain.
Mechanism of Action	P2Y12 receptor antagonists blocking ADP-mediated signaling
Druggability	Medium (0.55)
Clinical Stage	Approved
Pathways	PI3K, MAPK
UniProt ID	Q9H244
NCBI Gene ID	29128
Ensembl ID	ENSG00000170017
GeneCards	P2RY12
Human Protein Atlas	P2RY12
Associated Diseases	AD, Aging, Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	rapamycin, statins
Interactions	4E-BP1, ABCA1, ABCG1, ACTB, Actin, AD
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	Purinergic P2Y12 Inverse Agonist Therapy Microglial Purinergic Reprogramming P2RY12-mediated autophagy inhibition in cerebral V (+5 more)
KG Connections	633 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — P2RY12 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

4NTJ — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q9H244 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

P2RY12 Gene

gene · 1128 words

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Pathway Diagram

flowchart TD
    P2RY12["P2RY12
Microglial Receptor"]
    
    TREM2["TREM2
Microglial Activation"]
    Neuroinflammation["Neuroinflammation
Chronic Inflammation"]
    ALS["ALS
Motor Neuron Disease"]
    Neurodegeneration["Neurodegeneration
Neural Cell Death"]
    
    MTOR["mTOR
Growth Signaling"]
    ULK1["ULK1
Autophagy Initiator"]
    ATG5["ATG5
Autophagosome Formation"]
    LC3["LC3
Autophagosome Marker"]
    SQSTM1["SQSTM1/p62
Cargo Adapter"]
    Autophagy["Autophagy
Cellular Cleanup"]
    
    APOA1["APOA1
Cholesterol Transport"]
    ABCG1["ABCG1
Cholesterol Efflux"]
    Foam_Cell["Foam Cell
Formation"]
    Lipid_Accumulation["Lipid Accumulation
in Microglia"]
    
    P2RY12 -->|"expressed in"| TREM2
    P2RY12 -->|"biomarker for"| Neuroinflammation
    P2RY12 -->|"associated with"| ALS
    P2RY12 -->|"associated with"| Neurodegeneration
    
    P2RY12 -->|"inhibits"| MTOR
    P2RY12 -->|"inhibits"| ULK1
    P2RY12 -->|"inhibits"| ATG5
    P2RY12 -->|"activates"| LC3
    P2RY12 -->|"activates"| SQSTM1
    ULK1 -->|"initiates"| Autophagy
    ATG5 -->|"promotes"| Autophagy
    P2RY12 -->|"regulates"| Autophagy
    
    P2RY12 -->|"inhibits"| APOA1
    P2RY12 -->|"inhibits"| ABCG1
    P2RY12 -->|"promotes"| Foam_Cell
    P2RY12 -->|"promotes"| Lipid_Accumulation
    
    style P2RY12 fill:#006494
    style Autophagy fill:#1b5e20
    style APOA1 fill:#1b5e20
    style ABCG1 fill:#1b5e20
    style Neuroinflammation fill:#ef5350
    style ALS fill:#ef5350
    style Neurodegeneration fill:#ef5350
    style Foam_Cell fill:#ef5350
    style Lipid_Accumulation fill:#ef5350
    style TREM2 fill:#4a1a6b
    style MTOR fill:#4a1a6b
    style ULK1 fill:#4a1a6b
    style ATG5 fill:#4a1a6b
    style LC3 fill:#5d4400
    style SQSTM1 fill:#5d4400

Outgoing (330)

Target	Relation	Type	Str
ds-f2c28aed24a7	provides_data_for	dataset	1.00
platelet aggregation	regulates	process	0.95
UPREGULATES	upregulates	entity	0.95
LC3	inhibits	entity	0.90
SQSTM1	inhibits	entity	0.90
PI3K-AKT	activates	entity	0.90
autophagy	inhibits	process	0.90
Vsmc-Derived Foam Cell Formation	promotes	process	0.90
purinergic signaling	involved_in	pathway	0.90
ADCY	inhibits	protein	0.90
PIK3CA	activates	gene	0.85
microglia	expressed_in	cell_type	0.85
Microglia	biomarker_for	cell_type	0.80
Cholesterol Efflux	inhibits	process	0.80
MTOR	activates	gene	0.80
VSMC-derived foam cell formation	promotes	process	0.80
microglia activation	regulates	process	0.80
clopidogrel resistance	contributes_to	phenotype	0.80
microglial_process_motility	regulates	phenotype	0.80
apoptosis	protects_against	process	0.75
DAM microglia	expressed_in	cell_type	0.75
Als	associated_with	disease	0.75
SQSTM1	modulates	gene	0.75
purinergic signaling	participates_in	pathway	0.75
STING	disrupts	gene	0.70
lipid accumulation	activates	process	0.70
APOE	protects_against	gene	0.70
TAU	stabilizes	protein	0.70
APOE	inhibits	gene	0.70
middle_temporal_gyrus_aspiny_L3	expressed_in	cell_type	0.70
TAU	regulates	protein	0.70
autophagy	regulates	process	0.70
middle_temporal_gyrus_spiny_L3	expressed_in	cell_type	0.70
foam cell formation	regulates	process	0.70
middle_temporal_gyrus_spiny_L5	expressed_in	cell_type	0.70
PYROPTOSIS	inhibits	phenotype	0.70
ALS	inhibits	disease	0.65
ATHEROSCLEROSIS	treats	disease	0.65
ALS	associated_with	disease	0.65
Ptsd	associated_with	disease	0.65
Als	inhibits	disease	0.65
Inflammation	associated_with	disease	0.65
MTOR	causes	gene	0.65
Neuroinflammation	associated_with	disease	0.65
TAU	phosphorylates	protein	0.65
TREM2	associated_with	gene	0.65
Alzheimer	regulates	disease	0.65
APOE	treats	gene	0.65
Atherosclerosis	inhibits	disease	0.65
TAU	associated_with	gene	0.65

Incoming (311)

Source	Relation	Type	Str
ds-f2c28aed24a7	data_in	dataset	1.00
clopidogrel	targets	drug	0.95
ticagrelor	targets	drug	0.95
h-5daecb6e	targets_gene	hypothesis	0.90
h-f99ce4ca	targets_gene	hypothesis	0.90
MICROGLIA	expressed_in	entity	0.90
MACROPHAGE	expressed_in	entity	0.85
Acute Coronary Syndrome	therapeutic_target	disease	0.85
h-5daecb6e	targets	hypothesis	0.80
h-f99ce4ca	targets	hypothesis	0.80
MICROGLIA	causes	cell_type	0.70
APOE	expresses	gene	0.70
MACROPHAGE	stabilizes	cell_type	0.70
APP	markers	gene	0.70
Diabetes Mellitus	upregulates	disease	0.70
Chronic Kidney Disease	upregulates	disease	0.70
P2RX7	inhibits	gene	0.70
MICROGLIA	treats	cell_type	0.70
ATP	interacts_with	gene	0.65
ALS	activates	disease	0.65
AUTOPHAGY	associated_with	gene	0.65
APOE	associated_with	gene	0.65
MICROGLIA	associated_with	gene	0.65
ALZHEIMER	associated_with	gene	0.65
CX3CR1	associated_with	gene	0.65
ALZHEIMER'S DISEASE	interacts_with	disease	0.65
APOE	co_mentioned_with	gene	0.60
ATG5	co_discussed	gene	0.60
MTOR	co_discussed	gene	0.60
ABCA1	co_discussed	gene	0.60
P2RY1	activates	gene	0.60
MTOR	activates	gene	0.60
ABCA1	interacts_with	gene	0.60
ATG5	activates	gene	0.60
CD33	regulates	gene	0.60
CD44	regulates	gene	0.60
CD44	expressed_in	gene	0.60
AIF1	biomarker_for	gene	0.60
C1QA	biomarker_for	gene	0.60
C1QB	biomarker_for	gene	0.60
C1QC	biomarker_for	gene	0.60
C1R	biomarker_for	gene	0.60
C1S	biomarker_for	gene	0.60
C3	biomarker_for	gene	0.60
CHI3L1	biomarker_for	gene	0.60
CSF1R	biomarker_for	gene	0.60
GFAP	biomarker_for	gene	0.60
ITGAM	biomarker_for	gene	0.60
MAP2	biomarker_for	gene	0.60
MAPT	biomarker_for	gene	0.60

Targeting Hypotheses (19)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Purinergic P2Y12 Inverse Agonist Therapy	0.703	neurodegeneration	Synaptic pruning by microglia in early A
Microglial Purinergic Reprogramming	0.701	neurodegeneration	4R-tau strain-specific spreading pattern
TNF-α/NF-κB Axis Upregulates P2RY12 in VSMCs	0.650	neurodegeneration	What determines P2RY12 receptor expressi
P2RY12-mediated autophagy inhibition in cerebral VSMCs impai	0.605	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio
P2RY12-driven autophagy impairment in cerebral VSMCs mediate	0.585	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio

Pharmacological P2RY12 inhibition (ticagrelor/clopidogrel) a	0.583	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio
Female Microglia Exhibit Reduced P2Y12 Expression Conferring	0.580	neuroinflammation	How do regional, age, and sex-dependent
TREM2-P2RY12 Balance Restoration Therapy	0.571	neurodegeneration	Neuroinflammation and microglial priming
oxLDL/LOX-1/ROS Signaling Induces P2RY12 via Nrf2 Activation	0.550	neurodegeneration	What determines P2RY12 receptor expressi
miR-143/145 Cluster Dysregulation Derepresses P2RY12 Transcr	0.520	neurodegeneration	What determines P2RY12 receptor expressi
LRP1 Loss-of-Function Derepresses P2RY12 Expression	0.500	neurodegeneration	What determines P2RY12 receptor expressi
P2RY12/P2RY13 Purinergic Receptor Metabolic Rewiring	0.490	neuroinflammation	What molecular mechanisms mediate SPP1-i
Platelet-Derived PDGF-BB Primes VSMCs for P2RY12 Upregulatio	0.480	neurodegeneration	What determines P2RY12 receptor expressi
Cerebral VSMC foam cells induce pericyte detachment via PDGF	0.473	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio
KLF4-Mediated Transcriptional Repression of P2RY12	0.440	neurodegeneration	What determines P2RY12 receptor expressi
DNA Hypomethylation at P2RY12 Promoter Correlates with Disea	0.440	neurodegeneration	What determines P2RY12 receptor expressi
P2RY12-mediated cerebral VSMC dysfunction establishes a vici	0.418	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio
P2RY12 activation induces cellular senescence in cerebral VS	0.373	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio
P2RY12 rs2046934 polymorphism modifies neurodegeneration ris	0.273	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio

Mentioning Analyses (7)

Scientific analyses that reference this entity

Experiments (11)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
P2RY12 inhibition in atherosclerosis mouse model	validation	atherosclerosis	0.900	0.00	ApoE-deficient mice	proposed	N/A
VSMC cholesterol efflux and P2RY12 signaling	exploratory	atherosclerosis	0.900	0.00	cultured VSMCs	proposed	N/A
Leukocyte gene expression analysis in COVID-19 patients	exploratory	COVID-19	0.900	0.00	human leukocytes from COVID-19	proposed	N/A
P2RY12 regulation of autophagy in VSMCs	exploratory	atherosclerosis	0.900	0.00	cultured VSMCs	proposed	N/A
In vivo autophagy modulation in atherosclerotic mice	validation	atherosclerosis	0.850	0.00	ApoE-deficient mice	proposed	N/A
P2RY12-MTOR pathway interaction in VSMCs	exploratory	atherosclerosis	0.850	0.00	cultured VSMCs	proposed	N/A
s:** - GPR32 knockout in microglia should worsen neuroinflammation if	falsification	Neuroinflammation	0.400	0.50	cell_line	proposed	$80,000
Proposed experiment from debate on Synaptic pruning by microglia in ea	falsification	Neuroinflammation	0.400	0.50	mouse	proposed	$240,000
FTD Microglia Role: Protective vs Destructive Mechanism Study	validation	Neuroinflammation	0.400	0.50	human	proposed	$2,960,000
Purinergic Signaling Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
DLB Treatment Response Biomarkers — Predicting Cholinesterase Inhibito	clinical	Neurodegeneration	0.400	0.50	human	proposed	$6,550,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Beyond Activation: Characterizing Microglial Functional Phenotypes. [PMID:34571885]	Lier J, Streit WJ, Bechmann I	Cells	2021	2
The P2RY12 receptor promotes VSMC-derived foam cell formation by inhibiting auto [PMID:32160082]	Pi S, Mao L, Chen J, Shi H, Liu Y, Guo X	Autophagy	2021	2
Convergence between Microglia and Peripheral Macrophages Phenotype during Develo [PMID:31818979]	Grassivaro F, Menon R, Acquaviva M, Otto	J Neurosci	2020	1
Role of P2Y(12) Receptor in Thrombosis. [PMID:27628007]	Zhang Y, Zhang S, Ding Z	Adv Exp Med Biol	2017	1
P2 purinergic receptors in systemic lupus erythematosus: from experimental findi [PMID:41825304]	Renaudineau Y, Brooks W	Current opinion in immunology	2026	0
Constitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects [PMID:41924777]	Mroue-Ruiz FH, Desai B, Garvin MM, Shehu	Biochemical and biophysical re	2026	0
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
Targeting Itga8 Mitigates Neurogenic Bladder Fibrosis Driven by Trem2⁺ Macrophag [PMID:41355531]	Wang J, Wang S, Ren L, Liu X, Zhang L et	Adv Sci (Weinh)	2026	0
Hepatocyte Mettl3 Deficiency Drives Primary Sclerosing Cholangitis and Liver Fib [PMID:41431138]	Pan W, Yong Y, Li Y, Shi G, Zhang M et a	Adv Sci (Weinh)	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
Sulfatide deficiency-induced astrogliosis and myelin lipid dyshomeostasis are in [PMID:41513633]	He S, Mittra N, Bao H, Bhattacharjee A,	Nat Commun	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
The Dual Role of P2RY12: Impact of Polymorphism and Expression on Ischemic Event [PMID:41903930]	Li J, Gong Z, Wang S, Gu J, Wu S, Pang J	Journal of thrombosis and haem	2026	0
Association of P2Y12 Polymorphisms With the Risk of Ischemic Stroke Subtypes. [PMID:41761998]	Wu C, Chen Y, Chen J, Wei X, Zhang Z	Revista de neurologia	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
[Advantageous therapeutic pathways and mechanisms of Jianpi Huogu Formula in tre [PMID:41814722]	Li T, Zhang C, Jia Y, Chen WH, Lin N, Zh	Zhongguo Zhong yao za zhi = Zh	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

Debates (9)

Multi-agent debates referencing this entity

P2RY12

Understanding Entity Pages

Summary

Wiki Pages (1)

P2RY12 Gene

Pathway Diagram

Outgoing (330)

Incoming (311)

Targeting Hypotheses (19)

Mentioning Analyses (7)

What determines P2RY12 receptor expression/activity specifically in VSMCs during

How does P2RY12-mediated VSMC dysfunction contribute to cerebrovascular neurodeg

Neuroinflammation and microglial priming in early Alzheimer's Disease

Neuroinflammation and microglial priming in early Alzheimer's Disease

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Synaptic pruning by microglia in early AD

4R-tau strain-specific spreading patterns in PSP vs CBD

Experiments (11)

Related Papers (20)

Debates (9)

While the study establishes P2RY12's role in VSMC foam cell formation in atheros

The study shows P2RY12 regulates VSMC foam cell formation but doesn't explain wh

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

Investigate mechanistic links between early microglial priming states, neuroinfl

Investigate mechanistic links between early microglial priming states, neuroinfl

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

Synaptic pruning by microglia in early AD

Neuroinflammation and microglial priming in early Alzheimer's Disease

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD