Gene loci
- Chromosome 1p13.2.
Normal function
- Encodes small GTPase cycling between GDP-inactive and GTP-active forms, activates RAF/MEK/ERK, PI3K/AKT pathways regulating proliferation, survival, differentiation.
- Other RAS family genes
- HRAS: Bladder cancer
- KRAS: Colorectal Ca, Lung Ca
Mutation effects
- Point mutations (Q61R/K/L, G12D/V, G13D/R) impair GTPase activity, lock in GTP-bound state, constitutive activation of downstream effectors.
- Q61 mutations preferred in melanoma due to higher stability/oncometabolite.
Clinical association
- Melanoma
- 15-20%
- Q61 > G12/13
- Worse prognosis vs BRAF
- Acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), acute lymphoblastic leukemia (ALL), colorectal cancer, thyroid follicular neoplasm.
Targeted treatment
- Binimetinib
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