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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NETO1
neuropilin and tolloid like 1
Chromosome 18 · 18q22.3
NCBI Gene: 81832Ensembl: ENSG00000166342.20HGNC: HGNC:13823UniProt: Q8TDF5
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ionotropic glutamate receptor bindingmemoryvisual learningregulation of long-term neuronal synaptic plasticityalcohol drinkingexostosisadolescent idiopathic scoliosisfemoral neck fracture
✦AI Summary

NETO1 (neuropilin and tolloid-like 1) is a dual-function auxiliary subunit that modulates both N-methyl-D-aspartate receptors (NMDARs) and kainate receptors (KARs) at excitatory synapses. As an NMDAR accessory protein, NETO1 is critical for maintaining GRIN2A-containing NMDARs in the postsynaptic density and regulates NMDA receptor-dependent synaptic plasticity and spatial learning/memory 1. NETO1 functions through its CUB domains to interact with receptors and modulate their trafficking and localization 1. At KAR synapses, NETO1 regulates channel kinetics by slowing desensitization onset and accelerating recovery from desensitization in a subunit-dependent manner, with effects varying between GluK1 and GluK2 homomeric and heteromeric receptors 234. NETO1 is essential for synaptic KAR localization; Neto1-null mice show ~50% reduction in GluK2-KARs at postsynaptic densities and selective deficits in mossy fiber-CA3 kainate receptor-mediated transmission 1. Beyond neurotransmission, rare variants in NETO1 have been identified as candidate genetic risk factors in familial pulmonary fibrosis, suggesting broader physiological roles 5. This dual regulation of distinct glutamate receptor classes positions NETO1 as a critical determinant of excitatory synaptic strength and plasticity.

Sources cited
1
NETO1 is an auxiliary subunit for both NMDARs and KARs; maintains GluK2-KARs in postsynaptic densities; required for synaptic KAR function at mossy fiber-CA3 synapses
PMID: 21734292
2
NETO1 modulates KAR desensitization and recovery kinetics in subunit-dependent manner; distinct effects on GluK1 versus GluK2 receptors
PMID: 26277340
3
NETO1 decreases desensitization onset and speeds recovery from desensitization in homomeric and heteromeric KARs; effects independent of specific KAR subunit composition
PMID: 23798491
4
NETO1 slows channel-opening and channel-closing rates of GluK2 by approximately 2-fold
PMID: 41197725
5
Rare variants in NETO1 identified as candidate genes in familial pulmonary fibrosis genetic landscape study
PMID: 36622818
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.42Moderate
exostosisOpen Targets
0.33Weak
adolescent idiopathic scoliosisOpen Targets
0.33Weak
diaphragm diseaseOpen Targets
0.32Weak
femoral neck fractureOpen Targets
0.32Weak
Subdural hemorrhageOpen Targets
0.28Weak
kidney diseaseOpen Targets
0.25Weak
schizophreniaOpen Targets
0.20Weak
Abruptio PlacentaeOpen Targets
0.20Weak
Abnormal erythrocyte morphologyOpen Targets
0.20Weak
atrial heart septal defectOpen Targets
0.19Weak
placental retentionOpen Targets
0.19Weak
diabetes mellitusOpen Targets
0.19Weak
type 2 diabetes mellitusOpen Targets
0.19Weak
generalized dystoniaOpen Targets
0.18Weak
poisoningOpen Targets
0.17Weak
gastrointestinal diseaseOpen Targets
0.17Weak
HepatomegalyOpen Targets
0.17Weak
urinary tract obstructionOpen Targets
0.17Weak
respiratory system diseaseOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GRIK2Protein interaction91%GRIK1Protein interaction84%GRIN2AProtein interaction76%KARS1Protein interaction72%GRIK4Protein interaction71%TAFA2Shared pathway40%
Tissue Expression6 tissues
Brain
100%
Heart
6%
Bone Marrow
2%
Liver
0%
Lung
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
NETO1GRIK2GRIK1GRIN2AKARS1GRIK4TAFA2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8TDF5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.58Moderately Constrained
pLIⓘ
0.40Tolerant
Observed/Expected LoF0.40 [0.28–0.58]
RankingsWhere NETO1 stands among ~20K protein-coding genes
  • #12,397of 20,598
    Most Researched28
  • #3,925of 17,882
    Most Constrained (LOEUF)0.58 · top quartile
Genes detectedNETO1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The Genetic Landscape of Familial Pulmonary Fibrosis.
PMID: 36622818
Am J Respir Crit Care Med · 2023
1.00
2
Are Neto1 and APP auxiliary subunits of NMDA receptors?
PMID: 23815265
J Neurochem · 2013
0.90
3
Pharmacological Modulation of GluK1 and GluK2 by NETO1, NETO2, and PSD95.
PMID: 26991362
Assay Drug Dev Technol · 2016
0.80
4
Activation of kainate receptor GluK2-Neto2 complex.
PMID: 40846810
Nat Struct Mol Biol · 2025
0.70
5
The auxiliary subunits Neto1 and Neto2 have distinct, subunit-dependent effects at recombinant GluK1- and GluK2-containing kainate receptors.
PMID: 26277340
Neuropharmacology · 2015
0.60