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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NRTN
neurturin
Chromosome 19 · 19p13.3
NCBI Gene: 4902Ensembl: ENSG00000171119.4HGNC: HGNC:8007UniProt: Q99748
29PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
heparan sulfate bindingneural crest cell migrationneuron projection developmentgrowth factor activityrisk-taking behaviourduodenal ulcerage-related macular degenerationCOVID-19
✦AI Summary

NRTN encodes neurturin, a growth factor that supports the survival of sympathetic neurons and regulates CNS development and maintenance 1. NRTN functions by binding to its coreceptor GFRA2, leading to autophosphorylation and activation of the RET receptor, with heparan sulfate-binding required for signaling 234. Recent studies reveal NRTN's role in bone homeostasis, where it establishes a neurotrophic dependency between sympathetic cholinergic fibers and osteocytes through GFRα2-mediated signaling 5. In Parkinson's disease pathogenesis, NRTN serves as a neuroprotective factor produced by striatal interneurons and astrocytes through Hedgehog signaling, supporting dopaminergic neuron viability 67. Reduced NRTN expression contributes to disease progression when primary cilia formation is impaired by LRRK2 or GBA1 mutations 67. NRTN also shows clinical relevance in inflammatory conditions, with sputum NRTN levels correlating with Type 2 airway inflammation in asthma 8 and NRTN downregulation promoting allergic asthma through macrophage activation 9. In cancer, NRTN interacts with TANGO1 to promote hepatocellular carcinoma progression via PI3K/AKT/mTOR signaling 10. Gene therapy approaches targeting NRTN to the substantia nigra demonstrate neuroprotective effects in Parkinson's disease models 11.

Sources cited
1
NRTN supports sympathetic neuron survival and regulates CNS development
PMID: 8945474
2
NRTN binds to GFRA2 coreceptor leading to RET receptor activation
PMID: 10829012
3
Heparan sulfate-binding is required for NRTN signaling
PMID: 29414779
4
NRTN-GFRA2 interaction activates RET receptor
PMID: 31535977
5
NRTN establishes neurotrophic dependency between cholinergic fibers and osteocytes
PMID: 35276096
6
NRTN serves as neuroprotective factor in striatum supporting dopaminergic neurons
PMID: 40591712
7
NRTN production requires Hedgehog signaling and is reduced by GBA1 mutations
PMID: 40737317
8
Sputum NRTN levels correlate with Type 2 airway inflammation in asthma
PMID: 37671183
9
NRTN downregulation promotes allergic asthma through macrophage activation
PMID: 40467844
10
NRTN interacts with TANGO1 to promote hepatocellular carcinoma via PI3K/AKT/mTOR
PMID: 37211171
11
AAV2-NRTN gene therapy to substantia nigra provides neuroprotection
PMID: 21704161
Disease Associationsⓘ20
risk-taking behaviourOpen Targets
0.35Weak
duodenal ulcerOpen Targets
0.35Weak
age-related macular degenerationOpen Targets
0.16Weak
COVID-19Open Targets
0.16Weak
macular degenerationOpen Targets
0.12Weak
vitamin B deficiencyOpen Targets
0.11Weak
wet macular degenerationOpen Targets
0.10Weak
atrophic macular degenerationOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
Parkinson diseaseOpen Targets
0.04Suggestive
carcinomaOpen Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.03Suggestive
response to COVID-19 vaccineOpen Targets
0.02Suggestive
osteosarcomaOpen Targets
0.02Suggestive
asthmaOpen Targets
0.02Suggestive
Keratoconjunctivitis siccaOpen Targets
0.02Suggestive
Huntington diseaseOpen Targets
0.02Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
prostate cancerOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BDNFProtein interaction100%RETProtein interaction100%NTRK3Protein interaction97%SDC3Protein interaction83%NGFProtein interaction79%NTRK2Protein interaction79%
Tissue Expression6 tissues
Liver
100%
Heart
59%
Brain
39%
Lung
4%
Ovary
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
NRTNBDNFRETNTRK3SDC3NGFNTRK2
PROTEIN STRUCTURE
Preparing viewer…
PDB5NMZ · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.37Tolerant
Observed/Expected LoF0.37 [0.15–1.15]
RankingsWhere NRTN stands among ~20K protein-coding genes
  • #12,191of 20,598
    Most Researched29
  • #11,902of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedNRTN
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages.
PMID: 40467844
Commun Biol · 2025
1.00
2
TANGO1 interacts with NRTN to promote hepatocellular carcinoma progression by regulating the PI3K/AKT/mTOR signaling pathway.
PMID: 37211171
Biochem Pharmacol · 2023
0.90
3
A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.
PMID: 35276096
Cell Stem Cell · 2022
0.80
4
Restoration of striatal neuroprotective pathways by kinase inhibitor treatment of Parkinson's disease-linked
PMID: 40591712
Sci Signal · 2025
0.70
5
Sputum Neurturin Levels in Adult Asthmatic Subjects.
PMID: 37671183
J Asthma Allergy · 2023
0.60