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F877L Mutation

Meaning

The F877L Mutation is a specific, clinically significant point mutation in the androgen receptor (AR) gene, characterized by the substitution of the amino acid Phenylalanine (F) with Leucine (L) at position 877 of the AR protein sequence. This particular mutation occurs within the ligand-binding domain of the receptor, the pocket responsible for recognizing and binding androgen hormones and anti-androgen drugs. In prostate cancer, the presence of the F877L mutation is a known mechanism of acquired resistance to potent anti-androgen therapies like enzalutamide. This genetic alteration alters the receptor’s conformation, fundamentally changing its interaction with therapeutic agents.