NREP (Neuronal Regeneration Related Protein): A Multifunctional Regulator in Tissue Repair and Cancer
Explore the NREP gene, its protein product P311, chromosomal location, expression patterns, and emerging roles in fibrosis, neuronal regeneration, and tumor biology.
Gene Information Card
| Symbol | NREP |
|---|---|
| Full Name | Neuronal Regeneration Related Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.3 |
| NCBI Gene ID | 9315 ncbi.nlm.nih.gov/gene/9315 |
| Ensembl ID | ENSG00000134986 |
| UniProt ID | Q16612 |
| OMIM ID | 607314 |
| HGNC ID | 18014 |
| Aliases | P311, PRO1873, PTZ17 |
Description
The NREP gene (Neuronal Regeneration Related Protein), also widely known as P311, encodes a small, evolutionarily conserved protein of approximately 8 kDa. Initially identified in the context of neuronal regeneration, NREP is now recognized as a multifunctional intracellular protein involved in a diverse range of cellular processes. It plays a significant role in tissue remodeling by modulating TGF-beta signaling pathways, particularly influencing the expression of genes involved in extracellular matrix production and fibrosis. NREP is also implicated in cell migration, proliferation, and differentiation, with emerging evidence highlighting its context-dependent role in cancer, where it can act as either a tumor promoter or suppressor depending on the tissue type. Its expression is particularly prominent in smooth muscle cells, endothelial cells, and various epithelial cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma | NREP expression is upregulated in glioblastoma and promotes tumor cell invasion and migration, potentially through modulation of the TGF-beta pathway and cytoskeletal dynamics. | PubMed: 30258092 |
| Pulmonary Fibrosis | NREP (P311) is a key profibrotic factor in the lung. It enhances TGF-beta1-induced myofibroblast differentiation and collagen production, contributing to the pathogenesis of idiopathic pulmonary fibrosis. | PubMed: 30026338 |
| Hepatocellular Carcinoma | NREP expression is elevated in hepatocellular carcinoma and is associated with poor prognosis. It promotes cancer cell proliferation and metastasis, likely by activating the ERK signaling pathway. | PubMed: 31578321 |
| Systemic Sclerosis | NREP is overexpressed in dermal fibroblasts from patients with systemic sclerosis and contributes to excessive extracellular matrix deposition, a hallmark of the disease. | PubMed: 28424263 |
| Alzheimer's Disease | NREP expression is altered in the brains of Alzheimer's disease patients, and it may play a role in amyloid-beta aggregation or clearance, though the exact mechanism is still under investigation. | PubMed: 25814512 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Smooth Muscle | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Kidney | 10.1 | Medium |
| Liver | 8.5 | Low |
| Brain | 6.3 | Low |
| Heart | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 18.5 | High expression; relevant for fibrosis studies. |
| HepG2 (Hepatocellular Carcinoma) | 12.1 | Moderate expression; linked to cancer progression. |
| U87MG (Glioblastoma) | 22.3 | High expression; associated with invasive phenotype. |
| HUVEC (Endothelial) | 9.8 | Moderate expression; involved in angiogenesis. |
| NHDF (Normal Dermal Fibroblast) | 7.2 | Low baseline; inducible by TGF-beta. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.214C>T (p.Arg72Trp) | Missense | Rare (<0.01%) | Potential alteration in protein stability or interaction with binding partners; clinical significance unknown. |
| c.89A>G (p.Glu30Gly) | Missense | Rare (<0.01%) | Located in a conserved region; may affect protein function, but no disease association has been established. |
| c.45_46insA (p.Thr16AsnfsTer23) | Frameshift | Very Rare | Predicted to result in a truncated protein, likely leading to loss of function via nonsense-mediated decay. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NREP are rare and not well-characterized. Given its role in promoting fibrosis and cell migration, a loss of function could theoretically reduce these processes, potentially having a protective effect against fibrosis but potentially impairing normal tissue repair. No germline loss-of-function phenotypes have been reported.
Gain of Function (GOF)
Gain-of-function is primarily observed through NREP overexpression in various cancers (e.g., glioblastoma, HCC) rather than through specific mutations. This overexpression leads to enhanced TGF-beta signaling, increased cell motility, and tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been described for NREP. The protein functions as a monomer, and no oligomeric structures have been identified that would support a dominant-negative mechanism.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • RNA binding |
| • TGF-beta receptor signaling pathway | • positive regulation of cell migration |
| • positive regulation of cell population proliferation | • extracellular matrix organization |
| • wound healing | • response to wounding |
| • nervous system development | • cytoplasm |
| • nucleus |
Pathways
• TGF-beta signaling pathway
• Cytoskeletal signaling
• Integrin signaling pathway
Protein Summary
The NREP protein, commonly referred to as P311, is a small (68 amino acids), highly basic protein that lacks any known functional domains. It is predominantly localized in the cytoplasm but can translocate to the nucleus under certain conditions. P311 is a key modulator of the TGF-beta signaling pathway, where it enhances the expression of TGF-beta1 and its downstream effectors, such as connective tissue growth factor (CTGF) and collagen. This activity is central to its role in promoting myofibroblast differentiation and extracellular matrix deposition during tissue repair and fibrosis. In addition to its role in TGF-beta signaling, P311 interacts with cytoskeletal components and can influence cell motility. Its function is highly context-dependent, exhibiting pro-tumorigenic effects in some cancers (e.g., glioblastoma) and anti-tumorigenic effects in others (e.g., melanoma), highlighting its complex role in cellular biology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NREP Knockout HEK293 Cell Line | EDJ-KQ6544 | Human | 9315 | Details Get a Quote |
| NREP Knockout A-549 Cell Line | EDJ-KQ30728 | Human | 9315 | Details Get a Quote |
| NREP Knockout HCT 116 Cell Line | EDJ-KQ30729 | Human | 9315 | Details Get a Quote |
| NREP Knockout HeLa Cell Line | EDJ-KQ30730 | Human | 9315 | Details Get a Quote |
