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GeneE
6 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NTN3
netrin 3
Chromosome 16 · 16p13.3
NCBI Gene: 4917Ensembl: ENSG00000162068.2HGNC: HGNC:8030UniProt: O00634
16PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificRNA polymerase II transcription regulator complextrigeminal nerve diseasetrigeminal neuralgiaprostate cancercancer
✦AI Summary

NTN3 (netrin 3) is a secreted guidance molecule that functions as a ligand for the DCC dependence receptor, playing critical roles in both developmental and pathological contexts. In cancer biology, NTN3 promotes cell survival through DCC activation; elevated NTN3 expression has been observed in neuroendocrine neoplasms, small-cell lung cancer, and neuroblastoma, where it supports tumor growth 1. Blocking NTN3-DCC interaction using netrin-inhibiting antibodies suppresses pancreatic neuroendocrine neoplasm xenograft growth in vivo, with NTN3 expression inversely correlating with patient survival 1. NTN3 has also emerged as a potential biomarker in plasma extracellular vesicles for distinguishing early-stage lung adenocarcinoma from benign pulmonary nodules 2. During development, NTN3 contributes to axon guidance and plays a role in Hirschsprung disease pathogenesis as one of several genes involved in enteric neuron migration 3. Additionally, NTN3 accumulates in the detergent-insoluble proteome of Alzheimer's disease brains, suggesting involvement in protein aggregation pathology 4. These findings position NTN3 as a multifunctional protein with significance in developmental neurobiology, neurodegenerative disease, and cancer biology, representing a potential therapeutic target in neuroendocrine malignancies.

Sources cited
1
NTN3 is upregulated in neuroendocrine neoplasms; acts as DCC ligand promoting cell survival; blocking NTN3-DCC interaction suppresses tumor growth; NTN3 expression inversely correlates with survival
PMID: 41117212
2
NTN3 is upregulated in plasma extracellular vesicles and serves as a biomarker for distinguishing early-stage lung adenocarcinoma from benign pulmonary nodules
PMID: 41452660
3
NTN3 is one of several genes involved in the genetic etiology of Hirschsprung disease, affecting enteric neuron development
PMID: 15858239
4
NTN3 accumulates in the detergent-insoluble proteome of Alzheimer's disease brains, indicating involvement in protein aggregation pathology
PMID: 37356496
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
trigeminal nerve diseaseOpen Targets
0.03Suggestive
trigeminal neuralgiaOpen Targets
0.03Suggestive
prostate cancerOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.01Suggestive
diabetes mellitusOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
Cognitive impairmentOpen Targets
0.01Suggestive
small cell lung carcinomaOpen Targets
0.01Suggestive
Autosomal dominant polycystic kidney diseaseOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
neuroblastomaOpen Targets
0.00Suggestive
adrenal cortex carcinomaOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
metastatic neoplasmOpen Targets
0.00Suggestive
Mobius syndromeOpen Targets
0.00Suggestive
Parkinson diseaseOpen Targets
0.00Suggestive
prostate adenocarcinomaOpen Targets
0.00Suggestive
PainOpen Targets
0.00Suggestive
colorectal cancerOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NEO1Protein interaction99%UNC5CProtein interaction79%UNC5BProtein interaction75%DCCProtein interaction53%KIAA1755Shared pathway50%KLF7Shared pathway33%
Tissue Expression6 tissues
Liver
100%
Brain
91%
Bone Marrow
59%
Ovary
12%
Lung
12%
Heart
0%
Gene Interaction Network
Click a node to explore
NTN3NEO1UNC5CUNC5BDCCKIAA1755KLF7
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O00634
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.74LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.37 [1.08–1.74]
RankingsWhere NTN3 stands among ~20K protein-coding genes
  • #15,328of 20,598
    Most Researched16
  • #16,287of 17,882
    Most Constrained (LOEUF)1.74
Genes detectedNTN3
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
Netrin-DCC inhibition suppresses neuroendocrine neoplasm growth in vivo.
PMID: 41117212
Endocr Relat Cancer · 2025
1.00
2
Dissecting Detergent-Insoluble Proteome in Alzheimer's Disease by TMTc-Corrected Quantitative Mass Spectrometry.
PMID: 37356496
Mol Cell Proteomics · 2023
0.83
3
[The role of ret gene in the pathogenesis of Hirschsprung disease].
PMID: 15858239
Med Wieku Rozwoj · 2004
0.67
4
Proteomic Profiling of Plasma Extracellular Vesicles Combined with Multivariate Modeling Identified Potential Biomarkers for Distinguishing Benign Pulmonary Nodules from Early-Stage Lung Adenocarcinoma.
PMID: 41452660
J Proteome Res · 2026
0.50
5
MutLα suppresses error-prone DNA mismatch repair and preferentially protects noncoding DNA from mutations.
PMID: 38782208
J Biol Chem · 2024
0.33