NETO1 — Neuropilin and Tolloid Like 1

NETO1 — Neuropilin And Tolloid Like 1

<div class="infobox infobox-gene">
<div class="infobox-header">NETO1</div>

Overview

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[@stohr2002]. 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

<div class="infobox infobox-gene">
<div class="infobox-header">NETO1</div>

Overview

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[@stohr2002]. 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.

<div class="infobox-row"><span>Full Name:</span> Neuropilin and Tolloid Like 1</div>
<div class="infobox-row"><span>Symbol:</span> NETO1</div>
<div class="infobox-row"><span>Chromosomal Location:</span> 18q22.3</div>
<div class="infobox-row"><span>NCBI Gene ID:</span> <a href="https://www.ncbi.nlm.nih.gov/gene/63880" target="_blank">63880</a></div>
<div class="infobox-row"><span>OMIM:</span> <a href="https://www.omim.org/entry/607350" target="_blank">607350</a></div>
<div class="infobox-row"><span>Ensembl ID:</span> ENSG00000150045</div>
<div class="infobox-row"><span>UniProt:</span> <a href="https://www.uniprot.org/uniprot/Q9NUQ3" target="_blank">Q9NUQ3</a></div>
<div class="infobox-row"><span>Associated Diseases:</span> [Epilepsy](/diseases/epilepsy), [Alzheimer's Disease](/diseases/alzheimers-disease), [Autism Spectrum Disorder](/diseases/autism-spectrum-disorder), [Intellectual Disability](/diseases/intellectual-disability)</div>
</div>

Function

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[@stohr2002].

Structure

NETO1 contains:

• Multiple CUB domains (complement C1r/C1s, Uegf, Bmp1) for protein-protein interactions
• A single transmembrane domain
• A cytoplasmic tail with PDZ-binding motifs

Role in Synaptic Function

NETO1 is primarily expressed in the brain and localizes to excitatory synapses. It plays essential roles in:

Disease Associations

Epilepsy

NETO1 mutations are associated with epilepsy phenotypes:

• Childhood absence epilepsy
• Focal seizures
• Febrile seizures
• Lennox-Gastaut syndrome[@liu2023]

Alzheimer's Disease

NETO1 expression is altered in Alzheimer's disease:

• Reduced expression in hippocampal [neurons](/entities/neurons)
• Implicated in [amyloid-beta](/proteins/amyloid-beta) toxicity
• May affect glutamatergic signaling deficits

Autism Spectrum Disorder

Copy number variations and rare variants in NETO1 have been reported in ASD:

• Social and communication deficits
• Repetitive behaviors
• Comorbid intellectual disability

Intellectual Disability

NETO1 mutations can cause non-syndromic intellectual disability:

• Developmental delay
• Cognitive impairment
• Speech and language delays

Expression

NETO1 shows high expression in:

• [Hippocampus](/brain-regions/hippocampus) (CA1, CA3, dentate gyrus)
• Cerebral [cortex](/brain-regions/cortex) (layers 2/3, 5)
• Cerebellum (Purkinje cells)
• Basal ganglia
• Olfactory bulb

• Hippocampus: High in pyramidal neuron dendrites
• Cortex: Layer-specific expression in excitatory neurons
• Cerebellum: Purkinje cell layer

Common Variants

| 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 |

Therapeutic Implications

Target for Epilepsy

• Small molecule modulators of NETO1 function
• Gene therapy approaches to restore NETO1 expression
• Antisense oligonucleotides for variant-specific treatment

Alzheimer's Disease

• NETO1-enhancing compounds to restore synaptic function
• Modulation of glutamatergic signaling[@wang2024]

See Also

• [NETO2](/genes/neto2) — Neuropilin and Tolloid Like 2
• [GRIA1](/genes/gria1) — AMPA Receptor Subunit 1
• [GRIA2](/genes/gria2) — AMPA Receptor Subunit 2
• [Epilepsy](/diseases/epilepsy) — Epilepsy overview
• [Alzheimer's Disease](/diseases/alzheimers-disease) — AD overview

External Links

• [NCBI Gene: NETO1](https://www.ncbi.nlm.nih.gov/gene/63880)
• [UniProt: Q9NUQ3](https://www.uniprot.org/uniprot/Q9NUQ3)
• [OMIM: 607350](https://www.omim.org/entry/607350)
• [GeneCards: NETO1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=NETO1)

References