NETO2 — Neuropilin and Tolloid Like 2

NETO2 — Neuropilin And Tolloid Like 2

<div class="infobox infobox-gene">
<div class="infobox-header">NETO2</div>

Overview

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["@little2010"]. 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

<div class="infobox infobox-gene">
<div class="infobox-header">NETO2</div>

Overview

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["@little2010"]. 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.

<div class="infobox-row"><span>Full Name:</span> Neuropilin and Tolloid Like 2</div>
<div class="infobox-row"><span>Symbol:</span> NETO2</div>
<div class="infobox-row"><span>Chromosomal Location:</span> 16q23.1</div>
<div class="infobox-row"><span>NCBI Gene ID:</span> <a href="https://www.ncbi.nlm.nih.gov/gene/56604" target="_blank">56604</a></div>
<div class="infobox-row"><span>OMIM:</span> <a href="https://www.omim.org/entry/607972" target="_blank">607972</a></div>
<div class="infobox-row"><span>Ensembl ID:</span> ENSG00000167037</div>
<div class="infobox-row"><span>UniProt:</span> <a href="https://www.uniprot.org/uniprot/Q9H6X4" target="_blank">Q9H6X4</a></div>
<div class="infobox-row"><span>Associated Diseases:</span> [Epilepsy](/diseses/epilepsy), [Alzheimer's Disease](/diseases/alzheimers-disease), [Huntington's Disease](/diseases/huntingtons-disease), [Schizophrenia](/diseases/schizophrenia)</div>
</div>

Function

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[@little2010].

Structure

NETO2 contains:

• Two CUB domains (Complement C1r/C1s, Uegf, Bmp1) in the extracellular region
• A single transmembrane helix
• A cytoplasmic domain with PDZ-binding motifs

Role in Synaptic Transmission

NETO2 is critically involved in:

Disease Associations

Epilepsy

NETO2 variants are associated with epilepsy:

• Genetic epilepsy with generalized tonic-clonic seizures
• Febrile seizure susceptibility
• Absence epilepsy

Alzheimer's Disease

NETO2 expression changes in AD:

• Altered in prefrontal [cortex](/brain-regions/cortex)
• May contribute to excitatory/inhibitory imbalance
• Linked to amyloid pathology

Huntington's Disease

NETO2 is dysregulated in HD:

• Reduced expression in striatum
• May affect GABAergic signaling
• Contributes to network hyperexcitability

Schizophrenia

NETO2 associations with schizophrenia:

• Risk variants identified in GWAS
• Altered expression in prefrontal cortex
• Potential impact on glutamatergic signaling

Expression

NETO2 is highly expressed in:

• Brain cortex (layers 2-6)
• [Hippocampus](/brain-regions/hippocampus) (CA1, dentate gyrus)
• Cerebellum (Purkinje and granule cells)
• Basal ganglia (striatum)
• Olfactory bulb

• Cortex: Pyramidal [neurons](/entities/neurons), interneurons
• Hippocampus: Mossy fiber terminals
• Cerebellum: Molecular layer

Common Variants

| 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 |

Therapeutic Implications

Epilepsy Treatment

• NETO2 modulators to enhance inhibitory signaling
• Gene therapy approaches
• Small molecule targeting of NETO2-GABA interactions[@wu2023]

Neurodegenerative Diseases

• Restoring NETO2 expression in HD and AD
• Modulating excitatory/inhibitory balance

See Also

• [NETO1](/genes/neto1) — Neuropilin and Tolloid Like 1
• [GABRA1](/genes/gabra1) — GABA-A Receptor Alpha 1
• [GRIA2](/genes/gria2) — AMPA Receptor Subunit 2
• [Epilepsy](/diseases/epilepsy) — Epilepsy overview
• [Huntington's Disease](/diseases/huntington-disease) — HD overview

External Links

• [NCBI Gene: NETO2](https://www.ncbi.nlm.nih.gov/gene/56604)
• [UniProt: Q9H6X4](https://www.uniprot.org/uniprot/Q9H6X4)
• [OMIM: 607972](https://www.omim.org/entry/607972)
• [GeneCards: NETO2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=NETO2)

References