mechanism 1,071 words KG: ent-gene-12ded35c 2026-04-01
kind:mechanismsection:mechanismsstate:publishedtopic:causal-chainstopic:alzheimerstopic:synaptic-dysfunctiontopic:genetics
Contents

PTK2B→Pyk2→Synaptic Dysfunction→AD Causal Chain

🔬 Protein Info
Gene SymbolPTK2B (Protein Tyrosine Kinase 2 Beta)
Chromosome8p21.1
FunctionNon-receptor tyrosine kinase involved in synaptic plasticity, neuronal signaling, and cytoskeletal regulation
Primary ExpressionHighly expressed in neurons, particularly in hippocampal and cortical regions
Protein NamePyk2 (Proline-Rich Tyrosine Kinase 2)
Odds Ratio~1.10-1.15 per risk allele
Population FrequencyCommon variant (MAF ~20-30%)
Effect SizeModest but consistent across cohorts
MechanismRisk variants may affect gene expression or splicing in brain tissue
N-terminal FERM domainProtein-protein interactions, localization
Proline-rich regionSH3 domain binding (e.g., GRB2, p130Cas)
Kinase domainCatalytic activity (Y402 autophosphorylation site)
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

Knowledge Graph

Related Hypotheses (28)

TREM2-mediated microglial tau clearance enhancement
Score: 0.49
TREM2 Conformational Stabilizers for Synaptic Discrimination
Score: 0.41
SASP-Mediated Cholinergic Synapse Disruption
Score: 0.56
Targeted Butyrate Supplementation for Microglial Phenotype M
Score: 0.56
Vagal Afferent Microbial Signal Modulation
Score: 0.52

Related Analyses (30)

Sleep disruption as cause and consequence of neurodegenerati
neurodegeneration · archived
Synaptic pruning by microglia in early AD
neurodegeneration · archived
Circuit-level neural dynamics in neurodegeneration
neuroscience · archived
Tau propagation mechanisms and therapeutic interception poin
neurodegeneration · archived
SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas
neurodegeneration · completed

Related Experiments (5)

Cytochrome Therapeutics
clinical · proposed · Score: 0.40
Experiment: Multi-Ethnic PD GWAS
clinical · proposed · Score: 0.40
Microglial TREM2 Agonist In Vivo Efficacy
validation · proposed · Score: 0.40
TREM2 Agonist Therapy for Parkinson's Disease — Experimental
validation · proposed · Score: 0.40
TREM2 Function in Alzheimer's Disease — From Risk Variant to
validation · proposed · Score: 0.40