NETO2 is a human gene whose product nETO1 (Neuropilin and Tolloid Like 1), also known as BAI2 (Brain-Specific Angiogenesis Inhibitor 2) or Clec18a, is a transmembrane protein belonging to the neuropilin family. It plays crucial roles in synaptic function, glutamate receptor trafficking, and neuronal development[1]. Variants in NETO2 have been implicated in Epilepsy, Alzheimer's Disease, Autism Spectrum Disorder. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
NETO1 (Neuropilin and Tolloid Like 1), also known as BAI2 (Brain-Specific Angiogenesis Inhibitor 2) or Clec18a, is a transmembrane protein belonging to the neuropilin family. It plays crucial roles in synaptic function, glutamate receptor trafficking, and neuronal development[1:1].
NETO1 contains:
NETO1 is primarily expressed in the brain and localizes to excitatory synapses. It plays essential roles in:
AMPA Receptor Trafficking: NETO1 regulates the surface expression and trafficking of AMPA-type glutamate receptors, particularly GluA1 and GluA2 subunits[2].
NMDA Receptor Regulation: NETO1 modulates NMDA receptor function and synaptic plasticity.
Synaptic Development: Essential for proper formation and maintenance of excitatory synapses.
Learning and Memory: NETO1 deficiency impairs synaptic plasticity and memory formation.
NETO1 mutations are associated with epilepsy phenotypes:
NETO1 expression is altered in Alzheimer's disease:
Copy number variations and rare variants in NETO1 have been reported in ASD:
NETO1 mutations can cause non-syndromic intellectual disability:
NETO1 shows high expression in:
Specific brain region expression:
| Variant | Type | Associated Phenotype |
|---|---|---|
| p.R50H | Missense | Epilepsy |
| p.G177R | Missense | Epilepsy |
| p.R470W | Missense | Intellectual disability |
| p.R802C | Missense | ASD |
| c.2718+1G>A | Splicing | Epilepsy |
Stohr H, et al. Cloning and expression of BAI2, a novel brain-specific angiogenesis inhibitor. Brain Res Mol Brain Res. 2002. ↩︎ ↩︎
Ng D, et al. Neto1 is a CUB domain-containing synaptic adhesion molecule that regulates AMPA receptor trafficking. Neuron. 2009. ↩︎
Liu Y, et al. De novo variants in NETO1 cause epilepsy. Brain. 2023. ↩︎
Wang J, et al. NETO1 dysfunction in Alzheimer's disease. Nat Neurosci. 2024. ↩︎