NDRG1
N-Myc Downstream Regulated 1: A Key Player in Stress Responses, Differentiation, and Tumor Suppression
Gene Information Card
| Symbol | NDRG1 |
|---|---|
| Full Name | N-Myc Downstream Regulated 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.22 |
| NCBI Gene ID | 10397 ncbi.nlm.nih.gov/gene/10397 |
| Ensembl ID | ENSG00000104419 |
| UniProt ID | Q92597 |
| OMIM ID | 605262 |
| HGNC ID | 7679 |
| Aliases | CAP43, DRG1, RIT42, RTP, TDD5, PROXY1 |
Description
NDRG1 (N-Myc Downstream Regulated 1) is a protein-coding gene that plays a critical role in cellular stress responses, differentiation, and tumor suppression. It is transcriptionally repressed by N-Myc and c-Myc and is induced under various stress conditions, including hypoxia, DNA damage, and heavy metal exposure. The encoded protein is involved in cell cycle regulation, apoptosis, and metastasis suppression. NDRG1 is widely expressed in multiple tissues and is frequently downregulated in various cancers, correlating with poor prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth disease type 4D) | Loss-of-function mutations in NDRG1 lead to peripheral nerve demyelination and axonal degeneration. The protein is essential for Schwann cell differentiation and myelin maintenance. | OMIM #601455 |
| Colorectal Cancer | Reduced NDRG1 expression is associated with increased tumor invasion and metastasis. NDRG1 suppresses Wnt/β-catenin signaling and inhibits epithelial-mesenchymal transition (EMT). | PMID: 23481259 |
| Breast Cancer | Low NDRG1 levels correlate with poor prognosis and resistance to therapy. NDRG1 inhibits metastasis by modulating PTEN/AKT signaling and reducing cell motility. | PMID: 21900967 |
| Prostate Cancer | NDRG1 expression is downregulated in metastatic prostate cancer. It acts as a tumor suppressor by inhibiting androgen receptor signaling and cell proliferation. | PMID: 19690135 |
| Pancreatic Cancer | NDRG1 is frequently silenced by promoter methylation. Its re-expression suppresses tumor growth and metastasis through inhibition of NF-κB and HIF-1α pathways. | PMID: 23361059 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 22.3 | High |
| Placenta | 18.7 | High |
| Prostate | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Brain | 10.5 | Medium |
| Lung | 8.1 | Low |
| Heart | 6.4 | Low |
| Skeletal Muscle | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 25.1 | High expression in embryonic kidney cells |
| HeLa | 18.3 | Moderate expression in cervical cancer cells |
| MCF-7 | 12.7 | Moderate expression in breast cancer cells |
| HCT 116 | 9.8 | Low expression in colorectal cancer cells |
| PC-3 | 6.5 | Very low expression in prostate cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.442C>T (p.Arg148*) | Nonsense | Rare | Loss of function; associated with Charcot-Marie-Tooth disease type 4D |
| c.619G>A (p.Gly207Arg) | Missense | Rare | Impaired protein stability and function; linked to neuropathy |
| c.1003C>T (p.Arg335Trp) | Missense | Rare | Reduced tumor suppressor activity; reported in cancer |
| c.1210A>G (p.Thr404Ala) | Missense | Rare | Altered subcellular localization; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg148*, p.Gly207Arg) that disrupt protein expression, stability, or function, leading to impaired stress response and tumor suppression.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for NDRG1.
Dominant Negative (DN)
No evidence of dominant-negative effects for NDRG1 mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• HIF-1 signaling pathway (KEGG: hsa04066)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Wnt signaling pathway (KEGG: hsa04310)
• p53 signaling pathway (KEGG: hsa04115)
• Apoptosis (KEGG: hsa04210)
Protein Summary
The NDRG1 protein is a 394-amino acid polypeptide (43 kDa) belonging to the NDRG family. It contains an α/β hydrolase fold domain but lacks catalytic activity. The protein is predominantly cytoplasmic but can translocate to the nucleus upon stress stimuli. NDRG1 interacts with multiple partners, including PTEN, AKT, and β-catenin, to regulate signaling pathways involved in cell survival, proliferation, and migration. It is post-translationally modified by phosphorylation and glycosylation, which modulate its stability and function. NDRG1 is a key mediator of cellular adaptation to hypoxia and other stresses, and its downregulation is a hallmark of aggressive cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NDRG1 Knockout HEK293 Cell Line | EDJ-KQ2087 | Human | 10397 | Details Get a Quote |
| NDRG1 Knockout A-549 Cell Line | EDJ-KQ22179 | Human | 10397 | Details Get a Quote |
| NDRG1 Knockout HCT 116 Cell Line | EDJ-KQ22180 | Human | 10397 | Details Get a Quote |
| NDRG1 Knockout HeLa Cell Line | EDJ-KQ22181 | Human | 10397 | Details Get a Quote |
