Fatty acid amide hydrolase 1 (P129T mutant) (FAAH-1 P129T)

Fatty acid amide hydrolase 1 (FAAH-1) is the principal enzyme responsible for the metabolic inactivation of fatty acid amides, including the endocannabinoid anandamide (AEA) and the sleep-inducing lipid oleamide (Piomelli, 2003, Nature Reviews Neuroscience). The P129T mutant refers to a common human genetic polymorphism (rs324420) where a proline residue is replaced by threonine at position 129, leading to reduced protein stability and approximately 50% lower enzymatic activity (Chiang et al., 2004, Gene). This reduction in FAAH activity results in elevated baseline levels of anandamide, which significantly influences pain perception, emotional regulation, and reward processing (Hariri et al., 2009, Archives of General Psychiatry). Consequently, the P129T variant has been associated with various conditions, including substance abuse, obesity, and anxiety disorders (Sipe et al., 2002, PNAS). In the context of drug development, this mutant serves as a critical pharmacogenetic marker, as individuals carrying the P129T allele may exhibit different efficacy or safety profiles when treated with FAAH inhibitors currently being investigated for chronic pain and psychiatric conditions (Mayo et al., 2020, Molecular Psychiatry).

Other names

FAAH P129Trs324420Pro129Thr FAAHFatty-acid amide hydrolase 1 P129T variantFAAH 385C>A

Inhibition of fatty acid amide hydrolase to increase endogenous levels of N-acylethanolamines, particularly anandamide, to modulate cannabinoid receptor signaling.