NETO1 is a human gene whose product nETO2 (Neuropilin and Tolloid Like 2) is a transmembrane protein that plays important roles in synaptic function, neurodevelopment, and cell signaling. It is highly expressed in the central nervous system and participates in the regulation of glutamate receptor trafficking and synaptic plasticity[1]. Variants in NETO1 have been implicated in Epilepsy, Alzheimer's Disease, Huntington's Disease. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
NETO2 (Neuropilin and Tolloid Like 2) is a transmembrane protein that plays important roles in synaptic function, neurodevelopment, and cell signaling. It is highly expressed in the central nervous system and participates in the regulation of glutamate receptor trafficking and synaptic plasticity[1:1].
NETO2 contains:
NETO2 is critically involved in:
GABA Receptor Regulation: NETO2 modulates GABA-A receptor trafficking and function, influencing inhibitory synaptic transmission[2].
Glutamate Receptor Modulation: Regulates both AMPA and NMDA receptor surface expression.
Synaptic Plasticity: Essential for long-term potentiation (LTP) and depression (LTD).
Neurodevelopment: Involved in neurite outgrowth and synapse formation.
NETO2 variants are associated with epilepsy:
NETO2 expression changes in AD:
NETO2 is dysregulated in HD:
NETO2 associations with schizophrenia:
NETO2 is highly expressed in:
Regional expression patterns:
| Variant | Type | Associated Phenotype |
|---|---|---|
| p.R84Q | Missense | Epilepsy risk |
| p.E239K | Missense | Schizophrenia |
| p.G341S | Missense | Epilepsy |
| p.R518H | Missense | AD risk |
| c.1746-1G>C | Splicing | Epilepsy |
Little KD, et al. Identification and characterization of NETO2 in the nervous system. J Neurosci. 2010. ↩︎ ↩︎
Mahadevan V, et al. Neto2 modulates GABA-A receptor trafficking and function. J Neurosci. 2014. ↩︎
Wu Y, et al. NETO2 in epilepsy and neurodevelopmental disorders. Brain. 2023. ↩︎