SYNGAP1 haploinsufficiency in GABAergic interneurons causes circuit-level dysfunction by impairing developmental assembly rather than solely mature synaptic transmission.
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.78
Evidence
0.82
Novelty
0.65
Feasibility
0.58
Impact
0.72
Druggability
0.45
Safety
0.62
Competition
0.55
Data
0.85
Reproducible
0.88
Score Breakdown
Dimension
Interneuron SYNGAP1 Deficiency
Mechanistic
0.780
Evidence
0.820
Novelty
0.650
Feasibility
0.580
Impact
0.720
Druggability
0.450
Safety
0.620
Competition
0.550
Data
0.850
Reproducible
0.880
Evidence
Interneuron SYNGAP1 Deficiency Disrupts Cortical Circuit Ass
Supporting Evidence
Interneuron-specific SYNGAP1 disruption causes learning deficits and increased detrimental neuronal correlations in layePMID:37558489Zhao & Kwon, J Neurosci 2023
Developmental Syngap1 haploinsufficiency in MGE-derived interneurons impairs auditory cortex activity, social behavior, PMID:39406516Jadhav et al., J Neurosci 2024
Syngap1 regulates synaptic drive and membrane excitability of PV-positive interneurons in mouse auditory cortexPMID:40810392Francavilla et al., eLife 2025
SYNGAP1 is expressed in interneurons during development and disruption of D1R-SynGAP complexes alters GABAergic interneuPMID:31387938Su et al., Sci Signal 2019
SYNGAP1 interacts with NLGN3 (STRING score: 0.405), an autism-linked synaptic adhesion moleculecomputational:STRING_interaction_network
Contradicting Evidence
Circuit dysfunction without documented lamination defects suggests mechanism may be synaptic rather than purely migrator
The 'developmental window' prediction is unfalsifiable without adult rescue data
SYNGAP1's role in PV interneurons (PMID: 40810392) involves regulation of synaptic drive and membrane excitability—thesePMID:40810392
Knowledge Graph Comparison
Interneuron SYNGAP1 Deficiency Disrupts
1 edges
Top Node Types
gene1
Top Relations
promoted: Interneuron SYNGAP1 Deficiency Disrupts Cortical Circuit Assembly During Development1