ArticleMolecular psychiatry2011
A functional alternative splicing mutation in human tryptophan hydroxylase-2.
Article in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- High Prevalence of Severe Depression in Mexican Patients Diagnosed with HIV Treated with Efavirenz and Atazanavir: Clinical Follow-Up at Four Weeks and Analysis of TPH2 SNPs.Journal of clinical medicine · 2024Article
- In Vitro and In Vivo Chaperone Effect of (R)-2-amino-6-(1R, 2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one on the C1473G Mutant Tryptophan Hydroxylase 2.Biomolecules · 2023Article
- Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo.Translational psychiatry · 2023Article
- The Relationship Between Tryptophan Hydroxylase-2 Gene with Primary Insomnia and Depressive Symptoms in the Han Chinese PopulationBalkan medical journal · 2018Article
- A Novel Alternative Splicing Mechanism That Enhances Human 5-HT1A Receptor RNA Stability Is Altered in Major Depression.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences.Biochimica et biophysica acta · 2013Review
- Tryptophan hydroxylase-2: an emerging therapeutic target for stress disorders.Biochemical pharmacology · 2013Article
- Chronic SSRI treatment exacerbates serotonin deficiency in humanized Tph2 mutant mice.ACS chemical neuroscience · 2013Article
- A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.PloS one · 2013Article
- The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2012Review
- Selective deletion of forebrain glycogen synthase kinase 3β reveals a central role in serotonin-sensitive anxiety and social behaviour.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2012Article
- Advances in tryptophan hydroxylase-2 gene expression regulation: new insights into serotonin-stress interaction and clinical implications.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2012Review
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Authors and funding
15 authors at 9 institutions in 3 countries.
Funding
Abstract
The brain serotonergic system has an essential role in the physiological functions of the central nervous system and dysregulation of serotonin (5-HT) homeostasis has been implicated in many neuropsychiatric disorders. The tryptophan hydroxylase-2 (TPH2) gene is the rate-limiting enzyme in brain 5-HT synthesis, and thus is an ideal candidate gene for understanding the role of dysregulation of brain serotonergic homeostasis. Here, we characterized a common, but functional single-nucleotide polymorphism (SNP rs1386493) in the TPH2 gene, which decreases efficiency of normal RNA splicing, resulting in a truncated TPH2 protein (TPH2-TR) by alternative splicing. TPH2-TR, which lacks TPH2 enzyme activity, dominant-negatively affects full-length TPH2 function, causing reduced 5-HT production. The predicted mRNA for TPH2-TR is present in postmortem brain of rs1386493 carriers. The rs13864923 variant does not appear to be overrepresented in either global or multiplex depression cohorts. However, in combination with other gene variants linked to 5-HT homeostasis, this variant may exhibit important epistatic influences.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.