NDRG4
N-Myc Downstream Regulated Gene 4: A Key Player in Neuronal Development and Cancer
Gene Information Card
| Symbol | NDRG4 |
|---|---|
| Full Name | N-Myc Downstream Regulated Gene 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q21 |
| NCBI Gene ID | 65009 ncbi.nlm.nih.gov/gene/65009 |
| Ensembl ID | ENSG00000103044 |
| UniProt ID | Q9ULP0 |
| OMIM ID | 614273 |
| HGNC ID | 14465 |
| Aliases | SMAP-8, FLJ16103, MGC45416 |
Description
NDRG4 (N-Myc downstream regulated gene 4) encodes a member of the NDRG family of proteins, which are involved in cell growth, differentiation, and stress responses. The protein is predominantly expressed in the brain and heart, playing critical roles in neuronal development, axon guidance, and synaptic plasticity. NDRG4 is also implicated in tumor suppression and angiogenesis, with altered expression observed in various cancers and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Downregulation of NDRG4 promotes tumor growth and metastasis via activation of Wnt/β-catenin signaling. | ClinVar, COSMIC |
| Gastric Cancer | Reduced NDRG4 expression correlates with poor prognosis and increased cell proliferation through PI3K/AKT pathway modulation. | NCBI Gene, COSMIC |
| Glioblastoma | NDRG4 loss enhances tumor invasiveness and stemness by deregulating Notch signaling. | COSMIC, PubMed |
| Alzheimer's Disease | NDRG4 deficiency impairs synaptic function and promotes tau pathology. | OMIM, PubMed |
| Cardiovascular Disease | NDRG4 is essential for cardiac development; mutations linked to congenital heart defects. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 25.3 | High |
| Heart | 18.7 | High |
| Skeletal Muscle | 6.2 | Medium |
| Kidney | 4.1 | Low |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 22.1 | High expression; used in neuronal differentiation studies |
| HCT116 (colorectal carcinoma) | 3.8 | Low expression; associated with tumor progression |
| MCF7 (breast cancer) | 5.2 | Moderate expression; role in cell cycle regulation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon; likely loss of function |
| c.457C>T (p.Arg153Trp) | Missense | 0.2% | Alters protein stability; observed in colorectal cancer |
| c.832G>A (p.Gly278Arg) | Missense | 0.05% | Impaired interaction with binding partners; linked to neurological phenotypes |
Mutation functional classification
Loss of Function (LOF)
Mutations leading to reduced NDRG4 expression or protein truncation (e.g., p.Met1?) result in loss of tumor suppressor activity and enhanced cell proliferation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in NDRG4.
Dominant Negative (DN)
Not described for NDRG4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• PI3K/AKT signaling (KEGG: hsa04151)
• Notch signaling (KEGG: hsa04330)
Protein Summary
NDRG4 is a 340-amino acid protein belonging to the NDRG family. It contains an alpha/beta hydrolase fold but lacks catalytic activity. The protein is predominantly cytoplasmic and membrane-associated, interacting with multiple signaling molecules to regulate cell cycle, differentiation, and apoptosis. Post-translational modifications include phosphorylation and N-glycosylation, which modulate its stability and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NDRG4 Knockout HEK293 Cell Line | EDJ-KQ3874 | Human | 65009 | Details Get a Quote |
| NDRG4 Knockout A-549 Cell Line | EDJ-KQ26081 | Human | 65009 | Details Get a Quote |
| NDRG4 Knockout HCT 116 Cell Line | EDJ-KQ26082 | Human | 65009 | Details Get a Quote |
| NDRG4 Knockout HeLa Cell Line | EDJ-KQ26083 | Human | 65009 | Details Get a Quote |
