NTF4 (Neurotrophin 4)
Key regulator of neuronal survival, differentiation, and synaptic plasticity
Gene Information Card
| Symbol | NTF4 |
|---|---|
| Full Name | Neurotrophin 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 4909 ncbi.nlm.nih.gov/gene/4909 |
| Ensembl ID | ENSG00000104853 |
| UniProt ID | P34130 |
| OMIM ID | 162662 |
| HGNC ID | 8025 |
| Aliases | NT-4, NT-5, NTF5, GLC1O, neurotrophin-5 |
Description
NTF4 (Neurotrophin 4) encodes a member of the neurotrophin family that supports the survival, differentiation, and function of neurons. The protein binds preferentially to the TrkB receptor (NTRK2) and also to the p75 neurotrophin receptor (NGFR). NTF4 is involved in synaptic plasticity, axonal growth, and maintenance of the peripheral and central nervous systems. Mutations in NTF4 are associated with primary open-angle glaucoma (POAG).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary Open-Angle Glaucoma (POAG) | Loss-of-function mutations in NTF4 impair TrkB signaling, reducing neurotrophic support to retinal ganglion cells, leading to progressive optic neuropathy. | ClinVar, OMIM #162662 |
| Hereditary Sensory and Autonomic Neuropathy (HSAN) | Potential involvement via altered neurotrophin signaling, though direct evidence is limited. | NCBI Gene review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 1.2 | Low |
| Retina | 3.8 | Medium |
| Heart | 0.5 | Not detected |
| Liver | 0.1 | Not detected |
| Skeletal Muscle | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 2.1 | Neuronal model |
| ARPE-19 (retinal pigment epithelium) | 4.5 | Retinal expression |
| HEK293 (embryonic kidney) | 0.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3G>A (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.220C>T (p.Arg74Trp) | Missense | Rare | Impaired TrkB binding, associated with POAG |
| c.316C>T (p.Arg106Trp) | Missense | Rare | Reduced neurotrophic activity, POAG risk |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg74Trp and p.Arg106Trp reduce or abolish NTF4 binding to TrkB, impairing downstream survival signaling in retinal ganglion cells.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NTF4.
Dominant Negative (DN)
Heterozygous mutations may exert a dominant-negative effect by forming non-functional dimers or competing for TrkB binding, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0008083: growth factor activity | • GO:0005102: signaling receptor binding |
| • GO:0005163: nerve growth factor receptor binding | • GO:0042803: protein homodimerization activity |
| • GO:0007399: nervous system development | • GO:0043524: positive regulation of neuron apoptotic process |
| • GO:0030182: neuron differentiation |
Pathways
• Neurotrophin signaling pathway (KEGG: hsa04722)
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Apoptosis (KEGG: hsa04210)
Protein Summary
NTF4 is a secreted protein of 210 amino acids (precursor) that is proteolytically processed to a mature form of 130 amino acids. It contains a conserved cysteine-knot motif typical of neurotrophins. The mature protein forms homodimers and binds with high affinity to the TrkB receptor, activating downstream signaling cascades including MAPK/ERK and PI3K/Akt, promoting neuronal survival and differentiation. NTF4 also binds to the p75 neurotrophin receptor, which can modulate apoptosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NTF4 Knockout HEK293 Cell Line | EDJ-KQ718 | Human | 4909 | Details Get a Quote |
| NTF4 Knockout A-549 Cell Line | EDJ-KQ19339 | Human | 4909 | Details Get a Quote |
| NTF4 Knockout HCT 116 Cell Line | EDJ-KQ19340 | Human | 4909 | Details Get a Quote |
| NTF4 Knockout HeLa Cell Line | EDJ-KQ54028 | Human | 4909 | Details Get a Quote |
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