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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NTF4
neurotrophin 4
Chromosome 19 · 19q13.33
NCBI Gene: 4909Ensembl: ENSG00000225950.10HGNC: HGNC:8024UniProt: P34130
69PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnerve growth factor receptor bindinggrowth factor activitycell surface receptor protein tyrosine kinase signaling pathwaycanceropen-angle glaucomagenetic disordercorneal ulcer
✦AI Summary

NTF4 (neurotrophin 4) is a growth factor that primarily functions as a target-derived survival factor for peripheral sensory and sympathetic neurons 1. Beyond its classical neurotrophin role, emerging evidence reveals NTF4's unexpected involvement in multiple cancer types through distinct mechanisms. In cancer, NTF4 demonstrates a context-dependent dual functionality. In breast cancer, NTF4 paradoxically inhibits primary tumor proliferation and promotes apoptosis while simultaneously promoting epithelial-mesenchymal transition (EMT), metastatic progression, and invasiveness through PRKDC/AKT and ANXA1/NF-κB pathway activation 2. In non-small-cell lung cancer, gastric cancer, and colorectal cancer, NTF4 consistently promotes tumor development by negatively regulating FOXL1 and suppressing autophagy, with high NTF4 expression associated with poor prognosis and advanced disease stage 3456. Regarding glaucoma susceptibility, NTF4 mutations show population-specific associations. Chinese cohorts identified rare functional mutations (p.Gly157Ala, p.Ala182Val) in primary open-angle glaucoma (POAG) patients with impaired protein solubility 7, while Indian populations showed no significant association between NTF4 variants and glaucoma 8. Overall, NTF4 appears to function as an oncogene in solid tumors and a potential genetic risk factor for POAG.

Sources cited
1
NTF4 serves as a target-derived survival factor for peripheral sensory sympathetic neurons
PMID: 1742028
2
NTF4 has a dual role in breast cancer, promoting metastasis through EMT and PRKDC/AKT/ANXA1/NF-κB pathways while inhibiting primary tumor proliferation
PMID: 36632451
3
NTF4 promotes NSCLC proliferation and migration by negatively regulating FOXL1
PMID: 36034210
4
High NTF4 levels predict poor prognosis in gastric cancer and promote proliferation/migration via FOXL1 suppression
PMID: 34076998
5
NTF4 upregulation promotes colorectal cancer development through autophagy suppression and is associated with poor survival
PMID: 32236587
6
NTF4 mutations p.Gly157Ala and p.Ala182Val are functional mutations in Chinese POAG patients, affecting protein solubility and cell migration
PMID: 22815630
7
NTF4 variations show no significant association with glaucoma in Indian populations
PMID: 20463313
8
NTF4 is highly expressed in colorectal cancer and promotes CRC cell proliferation
PMID: 38159970
Disease Associationsⓘ21
cancerOpen Targets
0.38Weak
open-angle glaucomaOpen Targets
0.34Weak
genetic disorderOpen Targets
0.34Weak
corneal ulcerOpen Targets
0.15Weak
breast cancerOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
Romano-Ward syndromeOpen Targets
0.05Suggestive
PruritusOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
Spinocerebellar ataxia with axonal neuropathy type 2Open Targets
0.04Suggestive
Familial progressive cardiac conduction defectOpen Targets
0.04Suggestive
dystonia 23Open Targets
0.04Suggestive
proliferative diabetic retinopathyOpen Targets
0.04Suggestive
Combined hyperlipidemiaOpen Targets
0.04Suggestive
chronic kidney diseaseOpen Targets
0.04Suggestive
episodic ataxia type 1Open Targets
0.04Suggestive
gastric cancerOpen Targets
0.04Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.03Suggestive
arrhythmogenic right ventricular dysplasia 10Open Targets
0.03Suggestive
Glaucoma 1, open angle, OUniProt
Pathogenic Variants1
NM_006179.5(NTF4):c.521A>G (p.Gln174Arg)Likely pathogenic
Inborn genetic diseases
★☆☆☆2014→ Residue 174
View on ClinVar ↗
Related Genes
GDNFProtein interaction100%NGFRProtein interaction100%NTRK1Protein interaction100%SORT1Protein interaction100%EGFRProtein interaction100%NTRK2Protein interaction99%
Tissue Expression6 tissues
Lung
100%
Ovary
5%
Brain
1%
Bone Marrow
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
NTF4GDNFNGFRNTRK1SORT1EGFRNTRK2
PROTEIN STRUCTURE
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PDB1HCF · 2.70 Å · X-ray
View on RCSB ↗
RankingsWhere NTF4 stands among ~20K protein-coding genes
  • #6,827of 20,598
    Most Researched69
  • #5,004of 5,498
    Most Pathogenic Variants1
Genes detectedNTF4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NTF4 plays a dual role in breast cancer in mammary tumorigenesis and metastatic progression.
PMID: 36632451
Int J Biol Sci · 2023
1.00
2
The Role of Neurotrophin-4/Forkhead Box L1 in the Development of Nonsmall-Cell Lung Cancer.
PMID: 36034210
Contrast Media Mol Imaging · 2022
0.90
3
NTF4 stimulates the progression of gastric cancer via regulating FOXL1.
PMID: 34076998
J BUON · 2021
0.80
4
Variations in NTF4, VAV2, and VAV3 genes are not involved with primary open-angle and primary angle-closure glaucomas in an indian population.
PMID: 20463313
Invest Ophthalmol Vis Sci · 2010
0.70
5
Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy.
PMID: 32236587
Int J Oncol · 2020
0.60