NRAS
🔬 What is the NRAS Gene?
NRAS (Neuroblastoma RAS Viral Oncogene Homolog) is a proto-oncogene that encodes a GTPase, a type of protein involved in transmitting signals within cells (part of the RAS/MAPK pathway). This pathway regulates cell proliferation, differentiation, and survival.
NRAS belongs to the RAS gene family, along with KRAS and HRAS.
📊 How Prevalent Are NRAS Mutations in Cancer?
NRAS mutations are less common than KRAS mutations but still play a role in several cancers. Approximate prevalence by cancer type:
- Melanoma: ~15–20% of cases
- Acute Myeloid Leukemia (AML): ~10–15%
- Colorectal cancer: ~2–5%
- Thyroid cancer (especially follicular type): ~10–15%
- Lung cancer: <2%
⚙️ Mechanism: How NRAS Mutations Could Cause Cancer
1. Normal NRAS Function
NRAS cycles between an inactive GDP-bound state and an active GTP-bound state. When active, it sends signals through downstream pathways like:
- MAPK/ERK pathway → promotes cell proliferation
- PI3K/AKT pathway → promotes cell survival and growth
This cycling is tightly regulated in normal cells.
2. Mutated NRAS: “Always On”
Mutations in NRAS usually affect codons 12, 13, or 61. These changes:
- Prevent the hydrolysis of GTP to GDP
- Lock NRAS in a constitutively active (GTP-bound) state
- Result in constant signaling, even without growth signals
This uncontrolled signaling leads to:
- Unregulated cell proliferation
- Resistance to apoptosis (cell death)
- Increased potential for invasion and metastasis