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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NTF3
neurotrophin 3
Chromosome 12 · 12p13.31
NCBI Gene: 4908Ensembl: ENSG00000185652.12HGNC: HGNC:8023UniProt: P20783
121PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of MAPK cascaderegulation of apoptotic processprotein bindinggrowth factor activitycancerbreast carcinomaneuroendocrine neoplasmVon Willebrand disease
✦AI Summary

NTF3 (neurotrophin-3) is a nerve growth factor family member that functions primarily as a promoter of neuronal survival and development. During early neurogenesis, NTF3 acts as a key mediator of neuronal differentiation through transcriptional regulation by POU3F2, which directly binds the NTF3 promoter 1. NTF3 mediates its effects through receptor binding and activation of critical signaling cascades, including PI3K/AKT and MAPK pathways, which regulate neuronal cell viability, migration, and apoptotic resistance 2. Beyond the nervous system, NTF3 exhibits tumor-suppressive functions in hepatocellular carcinoma (HCC), where low expression correlates with shortened overall and disease-free survival 3. In HCC, NTF3 promotes apoptosis through p75NTR receptor binding and JNK/p38 MAPK pathway activation 4. Similarly, in cervical cancer, NTF3 functions as a direct target of miR-21, and its overexpression inhibits cell proliferation and migration while promoting apoptosis via PI3K-AKT and MAPK signaling 5. A regulatory long non-coding RNA, lnc-NTF3-5, modulates osteogenic differentiation and islet β-cell function through miRNA sponging mechanisms 6, 7. These findings establish NTF3 as a multi-functional growth factor with context-dependent roles in neuronal development and cancer suppression.

Sources cited
1
POU3F2 positively regulates NTF3 promoter activity during neuronal differentiation; NTF3 knockdown decreases neuronal cell viability and differentiation
PMID: 29549646
2
NTF3 mediates neuroprotection in intracerebral hemorrhage via PI3K/AKT pathway activation
PMID: 39690816
3
Low NTF3 expression in HCC correlates with shorter overall and disease-free survival; NTF3 is downregulated in HCC tissues
PMID: 33042332
4
NTF3 expression is lower in HCC tissue compared to para-cancerous tissue; NTF3 overexpression inhibits HCC cell proliferation
PMID: 37272057
5
miR-21 directly targets NTF3; NTF3 overexpression inhibits cervical cancer cell proliferation and migration while promoting apoptosis through PI3K-AKT and MAPK pathways
PMID: 39828780
6
Lnc-NTF3-5 regulates islet β-cell dysfunction; its manipulation affects cell proliferation, apoptosis, and insulin secretion in high glucose conditions
PMID: 31841205
7
Lnc-NTF3-5 promotes osteogenic differentiation by sponging miR-93-3p, which targets RUNX2
PMID: 29106055
8
NTF3 is a tumor suppressor in HCC that binds p75NTR and activates JNK/p38 MAPK pathways to induce apoptosis; low NTF3 expression associates with poor survival outcomes
PMID: 36263167
Disease Associationsⓘ20
cancerOpen Targets
0.38Weak
breast carcinomaOpen Targets
0.30Weak
neuroendocrine neoplasmOpen Targets
0.29Weak
Von Willebrand diseaseOpen Targets
0.23Weak
hemorrhageOpen Targets
0.21Weak
drug allergyOpen Targets
0.19Weak
gastric ulcerOpen Targets
0.19Weak
rhabdomyolysisOpen Targets
0.18Weak
diabetic ketoacidosisOpen Targets
0.18Weak
blood coagulation diseaseOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
liver diseaseOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
Mobius syndromeOpen Targets
0.08Suggestive
benign neoplasmOpen Targets
0.08Suggestive
nephrotic syndromeOpen Targets
0.08Suggestive
strokeOpen Targets
0.07Suggestive
KeloidOpen Targets
0.07Suggestive
Congenitally uncorrected transposition of the great arteriesOpen Targets
0.07Suggestive
ventricular septal defect 1Open Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GDNFProtein interaction100%NGFRProtein interaction100%NTRK1Protein interaction100%SORT1Protein interaction100%ERBB4Protein interaction100%FLT1Protein interaction99%
Tissue Expression6 tissues
Ovary
100%
Liver
79%
Heart
15%
Lung
10%
Brain
7%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
NTF3GDNFNGFRNTRK1SORT1ERBB4FLT1
PROTEIN STRUCTURE
Preparing viewer…
PDB9FIK · 1.86 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.29 [0.17–0.52]
RankingsWhere NTF3 stands among ~20K protein-coding genes
  • #3,887of 20,598
    Most Researched121 · top quartile
  • #3,209of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedNTF3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NTF3 Is a Novel Target Gene of the Transcription Factor POU3F2 and Is Required for Neuronal Differentiation.
PMID: 29549646
Mol Neurobiol · 2018
1.00
2
Esketamine Provides Neuroprotection After Intracerebral Hemorrhage in Mice via the NTF3/PI3K/AKT Pathway.
PMID: 39690816
CNS Neurosci Ther · 2024
0.90
3
Expression and prognostic impact of NTF3 and TrkC in hepatocellular carcinoma.
PMID: 37272057
Scand J Gastroenterol · 2023
0.80
4
miR-21 promotes cervical cancer by regulating NTF3.
PMID: 39828780
Sci Rep · 2025
0.70
5
Low expression of NTF3 is associated with unfavorable prognosis in hepatocellular carcinoma.
PMID: 33042332
Int J Clin Exp Pathol · 2020
0.60