NETO1 — Neuropilin and Tolloid Like 1

📖 Wiki Page

gene642 wordssynced 2026-04-02

NETO1 — Neuropilin And Tolloid Like 1

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

Overview

<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:

AMPA Receptor Trafficking: NETO1 regulates the surface expression and trafficking of AMPA-type glutamate receptors, particularly GluA1 and GluA2 subunits[@ng2009].

[NMDA Receptor](/entities/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.

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

Specific brain region expression:

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]

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

[Stohr H, et al, Cloning and expression of BAI2, a novel brain-specific angiogenesis inhibitor (2002)](https://pubmed.ncbi.nlm.nih.gov/12414119/)

[Ng D, et al, Neto1 is a CUB domain-containing synaptic adhesion molecule that regulates AMPA receptor trafficking (2009)](https://doi.org/10.1016/j.neuron.2008.12.006)

[Liu Y, et al, De novo variants in NETO1 cause epilepsy (2023)](https://doi.org/10.1093/brain/awad039)

[Wang J, et al, NETO1 dysfunction in Alzheimer's disease (2024)](https://doi.org/10.1038/s41593-023-01478-4)

📖 View canonical wiki page →

NETO1 — Neuropilin and Tolloid Like 1

NETO1 — Neuropilin And Tolloid Like 1

Overview

NETO1 — Neuropilin And Tolloid Like 1

Overview

Function

Structure

Role in Synaptic Function

Disease Associations

Epilepsy

Alzheimer's Disease

Autism Spectrum Disorder

Intellectual Disability

Expression

Common Variants

Therapeutic Implications

Target for Epilepsy

Alzheimer's Disease

See Also

External Links

References