Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression

@article{Zhang2005LossofFunctionMI,
  title={Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression},
  author={X. Zhang and R. Gainetdinov and J. Beaulieu and T. Sotnikova and L. Burch and R. B. Williams and D. Schwartz and K. Krishnan and M. Caron},
  journal={Neuron},
  year={2005},
  volume={45},
  pages={11-16}
}
Dysregulation of central serotonin neurotransmission has been widely suspected as an important contributor to major depression. Here, we identify a (G1463A) single nucleotide polymorphism (SNP) in the rate-limiting enzyme of neuronal serotonin synthesis, human tryptophan hydroxylase-2 (hTPH2). The functional SNP in hTPH2 replaces the highly conserved Arg441 with His, which results in approximately 80% loss of function in serotonin production when hTPH2 is expressed in PC12 cells. Strikingly… Expand
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