During carcinogenesis, a point mutation in codon 12 of the KRAS gene results in substitution of glycine by valine. The key functional consequence of this mutation is:

• A Loss of intrinsic GTPase activity, locking RAS in the active GTP-bound state ✓
• B Constitutive activation of GTPase activity of RAS protein
• C Inability of RAS to bind GTP, silencing downstream signaling
• D Overexpression of wild-type RAS protein by gene amplification

Explanation

Normal RAS protein cycles between inactive GDP-bound and active GTP-bound states; intrinsic GTPase activity hydrolyzes GTP to GDP, terminating signaling. Codon 12 mutations (most commonly Gly→Val or Gly→Asp) abolish this GTPase activity, trapping RAS in the active GTP-bound state and constitutively driving proliferative signaling through RAF-MEK-ERK and PI3K-AKT pathways. This is a gain-of-function oncogenic mutation, not loss-of-function or amplification.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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