Affinage

TPH1

Tryptophan 5-hydroxylase 1 · UniProt P17752

Length
444 aa
Mass
51.0 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPH1 is the nonneuronal isoform of tryptophan hydroxylase that catalyzes the rate-limiting step in peripheral serotonin (5-HT) biosynthesis, expressed in the pineal gland and enterochromaffin cells, where its genetic inactivation depletes peripheral 5-HT and produces cardiac dysfunction and heart failure (PMID:14597720). Its transcription is driven through the proximal promoter by cooperative binding of NF-Y to an inverted CCAAT box and Sp1 to an adjacent GC-rich element, which together support both basal expression and CRE-independent cAMP activation (PMID:12065627), and is further modulated by stimulus-specific transcription factors including glucose-activated CREB in pancreatic β-cells (PMID:28794173) and a PKA axis that is repressed when HDAC1 deacetylates the PKA catalytic subunit (PMID:32641996). TPH1 protein output is acutely tuned post-translationally: phosphorylation at Ser58 stabilizes the protein and drives the nocturnal surge in pineal 5-HT synthesis (PMID:18705647). Through its 5-HT product, TPH1 acts as a central effector across peripheral tissues—amplifying glucose-stimulated insulin secretion in β-cells, with β-cell-specific knockout causing glucose intolerance (PMID:32641996), contributing circulating serotonin during lactation (PMID:29123193), promoting hypoxia-induced pulmonary vascular remodeling (PMID:22525513), and driving bleomycin-induced pulmonary fibrosis (PMID:29849496) and Wnt/β-catenin-dependent renal fibrosis (PMID:33062239). Studies of the C. elegans tph-1 ortholog establish a conserved logic of cell-specific and experience-dependent transcriptional control by the POU-domain factor UNC-86 and by CaMKII/Gqα signaling (PMID:23325232, PMID:12135927).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Defining how TPH1 is transcribed established the basal and cAMP-responsive promoter logic of serotonin biosynthesis, answering whether activation required a canonical CRE.

    Evidence Promoter mutagenesis, EMSA, and transactivation assays in pinealocytes

    PMID:12065627

    Open questions at the time
    • Does not identify the factor transducing cAMP to the NF-Y/Sp1 complex
    • Restricted to the pineal context
  2. 2002 High

    Genetic dissection in C. elegans showed cell-specific transcriptional control of the tph-1 ortholog, establishing that serotonin synthesis and vesicular transport can be coordinately regulated by a single transcription factor.

    Evidence unc-86 null mutants with cell-type-specific reporter and reuptake assays in C. elegans

    PMID:12135927

    Open questions at the time
    • Mammalian relevance of UNC-86 orthologs to TPH1 not addressed
    • Mechanism of cell-specificity at the promoter not resolved
  3. 2003 High

    Knockout established TPH1 as the nonneuronal, peripheral serotonin-synthesizing isoform and tied its loss to a concrete cardiac phenotype, distinguishing it from neuronal serotonin synthesis.

    Evidence tph1-/- mice via beta-galactosidase replacement, reporter expression mapping, hemodynamic analysis

    PMID:14597720

    Open questions at the time
    • Mechanism linking peripheral 5-HT loss to cardiac dysfunction not defined
    • Does not address enzymatic kinetics
  4. 2008 High

    Identifying Ser58 phosphorylation revealed how TPH1 activity is acutely controlled post-translationally, explaining the cAMP-driven nocturnal surge in pineal serotonin output.

    Evidence In vitro and in vivo phosphosite mapping, Ser58 mutagenesis, cAMP stimulation, protein stability and 5-HT output assays

    PMID:18705647

    Open questions at the time
    • Kinase responsible for Ser58 phosphorylation not identified
    • Structural basis of stabilization unknown
  5. 2008 Medium

    Stress-induced upregulation of TPH1 mRNA in the raphe established a stress-specific, isoform-selective transcriptional response distinct from TPH2.

    Evidence qPCR and in situ hybridization in restraint-stressed rats

    PMID:18197473

    Open questions at the time
    • Upstream signaling driving the induction not identified
    • Functional consequence of low-level raphe TPH1 unclear
  6. 2012 Medium

    Cell-targeted knockdown placed endothelial TPH1-derived serotonin causally upstream of hypoxic pulmonary vascular remodeling.

    Evidence ACE-targeted bispecific antibody adenoviral shRNA knockdown in PAECs, conditioned media on SMCs, hypoxic PAH rat model

    PMID:22525513

    Open questions at the time
    • Downstream serotonin receptor on smooth muscle not defined
    • Single lab
  7. 2017 Medium

    Glucose-driven CREB activation and β-cell serotonin synthesis defined a metabolic feed-forward loop in which TPH1 amplifies insulin secretion.

    Evidence Islet expression profiling, CREB promoter binding, Tph1 knockdown/overexpression, in vivo glucose infusion and insulin assays

    PMID:28794173

    Open questions at the time
    • How serotonin acts autocrine/paracrine on secretion not fully mapped
    • Single lab
  8. 2017 Medium

    Mammary-specific knockout quantified an unexpected tissue source of circulating serotonin, showing TPH1 contributions are tissue- and state-dependent.

    Evidence WAP-Cre conditional Tph1 KO with serotonin measurements in tissue and serum during lactation

    PMID:29123193

    Open questions at the time
    • Physiological role of lactation-derived serum serotonin not established
    • Single lab
  9. 2018 Medium

    TPH1 knockout protection against bleomycin injury established TPH1-derived serotonin as a driver of pulmonary fibrosis and associated inflammation/oxidative stress.

    Evidence Tph1 KO mice with bleomycin instillation, hydroxyproline, cytokine, and fibrosis marker readouts

    PMID:29849496

    Open questions at the time
    • Cellular source of pro-fibrotic serotonin not pinpointed
    • Receptor mediating fibrotic effect not identified
  10. 2020 High

    Discovery of HDAC1-mediated PKA deacetylation defined a layer of TPH1 transcriptional repression and confirmed β-cell TPH1's role in glucose homeostasis.

    Evidence Co-IP, PKA K62Q acetyl-mimetic mutant, adenoviral OE/KD, β-cell-specific Tph1 KO mice and transgenic rats, metabolic phenotyping

    PMID:32641996

    Open questions at the time
    • How PKA activity feeds into the NF-Y/Sp1 promoter module not detailed
    • Single lab
  11. 2020 Medium

    Placing TPH1 upstream of β-catenin stability identified an anti-fibrotic signaling role in chronic kidney disease distinct from its pro-fibrotic lung action.

    Evidence Lentiviral OE/KD, luciferase reporter, Co-IP, UUO and adenine CKD models, TGF-β1 cell lines

    PMID:33062239

    Open questions at the time
    • Mechanism by which serotonin/TPH1 controls β-catenin stability unresolved
    • Tissue-dependent opposite fibrotic effects unexplained
  12. 2020 Medium

    Identification of TPH1 in astrocytes downstream of PAC1R/JNK extended its role to a cytoprotective antioxidant response in glial cells.

    Evidence Primary astrocyte culture, RT-PCR, immunofluorescence, lentiviral TPH1 KD, viability assays

    PMID:36037970

    Open questions at the time
    • Direct transcriptional link from JNK to TPH1 promoter not shown
    • Single lab
  13. 2021 Medium

    EZH2 acting non-canonically as a scaffold for methylated NF-κB/Sp1 to drive TPH1 in PDAC connected TPH1 to chemoresistance and cancer stemness.

    Evidence Co-IP with methyl-lysine antibodies, siRNA KD, GSK-126, xenografts, CSC flow cytometry

    PMID:34771469

    Open questions at the time
    • Direct EZH2 occupancy at the TPH1 promoter not demonstrated
    • Single lab
  14. 2024 Low

    A microbial-metabolite/AhR axis was linked to mast-cell TPH1 induction, proposing a tolerogenic serotonin pathway in autoimmunity.

    Evidence Ex vivo lymph node and mast cell assays with 3-IAld, AhR pathway analysis, serum metabolite correlation in MS

    PMID:38509264

    Open questions at the time
    • No direct promoter or knockout experiment demonstrating AhR control of Tph1
    • Causal contribution to MS not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple upstream transcriptional inputs (NF-Y/Sp1, CREB, PKA/HDAC1, EGR-1, EZH2, AhR) and the Ser58 phosphorylation switch are integrated to set tissue-specific TPH1 levels, and how 5-HT receptor downstream effectors mediate the divergent cardiac, metabolic, and fibrotic outcomes, remains unresolved.
  • No unified model linking promoter inputs across tissues
  • Kinase for Ser58 unidentified
  • Receptor-level effectors of TPH1-derived 5-HT not mapped per tissue

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Genetic knockout of tph1 in mice (replacement with beta-galactosidase gene) demonstrated that TPH1 is the nonneuronal isoform expressed in pineal gland and enterochromaffin cells (not in raphe neurons), and that loss of peripheral serotonin via tph1 inactivation causes cardiac dysfunction and heart failure, establishing TPH1's essential role in peripheral 5-HT synthesis. Knock-in/knockout mouse model (tph1-/- via beta-galactosidase replacement), beta-galactosidase reporter expression mapping, hemodynamic analysis Proceedings of the National Academy of Sciences of the United States of America High 14597720
2008 TPH1 protein is phosphorylated at serine 58 in vitro and in the rat pineal gland at night; this phosphorylation is required for cAMP-enhanced TPH1 protein stability and is responsible for the nocturnal surge in 5-HT synthesis in the pineal gland. Phosphorylation site mapping in vitro and in vivo, mutagenesis of Ser58, cAMP stimulation assays, TPH1 protein stability measurements, 5-HT output quantification Journal of pineal research High 18705647
2002 Transcription of the TPH1 gene in the pineal gland requires cooperative binding of NF-Y to an inverted CCAAT box and Sp1 to an adjacent GC-rich region in the proximal promoter; both elements are essential for full basal transcription and for cAMP-mediated transcriptional activation via a CRE-independent pathway. Promoter deletion/mutation analysis, electrophoretic mobility shift assay (EMSA), transactivation assays in pinealocytes, co-transfection with NF-Y and Sp1 expression vectors Journal of neurochemistry High 12065627
2013 In C. elegans, experience-dependent transcription of tph-1 in ADF serotonergic neurons is regulated by CaMKII (UNC-43), which acts cell-autonomously to increase ADF neuronal activity and tph-1 transcription; upstream, the Gqα protein EGL-30 facilitates this induction through regulation of olfactory sensory neurons. Genetic epistasis (null mutants, activated-form transgenes), cell-specific rescue experiments, neuronal activity assays, transcriptional reporter assays in C. elegans The Journal of neuroscience High 23325232
2002 In C. elegans, the POU-domain transcription factor UNC-86 is required cell-specifically for tph-1 expression in NSM serotonergic neurons but not in ADF neurons, and coordinately regulates both tph-1 (serotonin synthesis) and cat-1 (vesicular monoamine transporter) in a cell-specific manner, while serotonin reuptake in NSM is regulated independently. Genetic null mutants (unc-86), in situ hybridization and reporter assays for tph-1 and cat-1, pharmacological reuptake inhibition (imipramine, fluoxetine) Development (Cambridge, England) High 12135927
2008 In the rat dorsal raphe nucleus (DRN), TPH1 mRNA (low basal level) is upregulated 2.5-fold by one week of daily restraint stress, whereas TPH2 mRNA is not affected by stress in either DRN or pineal gland, indicating a stress-specific regulation of TPH1 in serotonergic neurons. Quantitative real-time PCR, in situ hybridization, restraint stress paradigm in rats Cellular and molecular neurobiology Medium 18197473
1994 Reduction of serotonin levels by PCPA-mediated irreversible inhibition of TPH activity leads to early upregulation of TPH mRNA (detectable by in situ hybridization), suggesting end-product (5-HT) feedback repression of tph1 gene transcription; AADC mRNA was unaffected, indicating specificity. PCPA pharmacological depletion, in situ hybridization for TPH and AADC mRNA, immunohistochemistry for 5-HT Brain research. Molecular brain research Medium 8015380
2012 Targeted adenoviral knockdown of Tph1 specifically in pulmonary arterial endothelial cells (using an ACE-targeted bispecific antibody delivery system) attenuated hypoxia-induced pulmonary arterial hypertension in rats, demonstrating that endothelial Tph1-derived serotonin contributes to hypoxic vascular remodeling. Adenoviral shRNA knockdown targeted to PAECs via bispecific antibody, conditioned media experiments on smooth muscle cells, in vivo hypoxic PAH model in rats Molecular therapy Medium 22525513
2017 Glucose induces Tph1 expression in pancreatic β-cells via synergistic calcium and cAMP signals that activate CREB and promote its binding to the Tph1 promoter; Tph1-derived serotonin amplifies glucose-stimulated insulin secretion, and Tph1 knockdown reduces glucose-potentiated insulin secretion. Gene expression profiling in rat islets, CREB promoter binding assays, Tph1 knockdown/overexpression, in vivo glucose infusion, insulin secretion assays FASEB journal Medium 28794173
2020 HDAC1 deacetylates the PKA catalytic subunit (at K62), reducing its activity and thereby repressing Tph1 transcription in pancreatic β-cells; HDAC1 inhibition derepresses PKA-driven Tph1 expression and serotonin synthesis, amplifying insulin secretion. β-cell-specific Tph1 knockout mice display glucose intolerance and impaired insulin secretion with aging. Co-immunoprecipitation, adenoviral overexpression/knockdown, PKA acetylation-mimetic mutant (K62Q), β-cell-specific Tph1 KO mice and Tph1 transgenic rats, glucose tolerance and insulin secretion assays Theranostics High 32641996
2017 Mammary-specific conditional knockout of Tph1 (WAP-Cre × Tph1 FL/FL) during lactation decreased serotonin in both mammary gland and serum, demonstrating that mammary-derived TPH1 is a significant contributor to circulating serotonin concentrations during lactation. Conditional knockout (WAP-Cre cre-lox), serotonin measurements in mammary tissue and serum, comparison with Lrp5 conditional KO Scientific reports Medium 29123193
2018 TPH1 knockout mice exposed to bleomycin exhibited significantly less pulmonary fibrosis than wild-type mice, with reduced hydroxyproline content, lower inflammatory cytokines (TNF-α, IL-6), reduced oxidative stress markers, and lower fibrosis-associated protein expression, demonstrating that TPH1-derived peripheral serotonin promotes bleomycin-induced pulmonary fibrosis. TPH1 knockout mouse model, bleomycin intratracheal instillation, histology (H&E, Sirius Red), hydroxyproline assay, cytokine measurement, Western blot Mediators of inflammation Medium 29849496
2020 TPH1 is expressed in rat astrocytes; peptide OM-LV20 upregulates TPH1 expression via the PAC1R/JNK signaling axis, and this TPH1 upregulation mediates the protective effect of OM-LV20 against hydrogen peroxide-induced oxidative stress in astrocytes. Primary astrocyte culture, quantitative RT-PCR, double immunofluorescence, lentiviral knockdown of TPH1, cell viability assays, Western blot for PAC1R and JNK pathway The Journal of biological chemistry Medium 36037970
2020 TPH1 expression is gradually decreased during chronic kidney disease progression; pharmacological overexpression of TPH1 by poricoic acid A (PAA) suppresses renal fibrosis by inhibiting Wnt/β-catenin signaling through regulation of β-catenin protein stability. TPH1 overexpression enhanced and TPH1 deficiency weakened PAA's anti-fibrotic effects, placing TPH1 upstream of β-catenin stabilization. Lentiviral overexpression/knockdown of TPH1, luciferase reporter assay, co-immunoprecipitation, unilateral ureteral obstruction and adenine-induced CKD mouse models, TGF-β1-treated cell lines Therapeutic advances in chronic disease Medium 33062239
2021 In pancreatic ductal adenocarcinoma (PDAC) cells, EZH2 acts non-canonically as a scaffold binding methylated NF-κB and Sp1 (and unmethylated p-STAT3) to drive TPH1 and 5-HT7 receptor expression; knockdown of EZH2 reduces TPH1 expression via PI3K/Akt and JAK2/STAT3 pathways, and EZH2 or TPH1 knockdown restores gemcitabine sensitivity and reduces cancer stem cell populations. Co-immunoprecipitation with EZH2 and pan-methyl-lysine antibodies, siRNA knockdown, GSK-126 inhibitor treatment, xenograft tumor model, flow cytometry for CSCs Cancers Medium 34771469
2013 The TPH1 proximal promoter SNP -347C/A (rs7130929) differentially binds early growth response factor 1 (EGR-1), with higher affinity to the minor A-allele, as shown by electrophoretic mobility shift assay, suggesting this variant modulates EGR-1-dependent TPH1 transcription in enterochromaffin cells. Electrophoretic mobility shift assay (EMSA), genotyping in IBS patients, colonic biopsy mRNA expression analysis The American journal of gastroenterology Low 24060757
2011 Chromosomal localization of the human TPH gene was refined by in situ hybridization to chromosome 11p15.3–p14. In situ hybridization to human chromosomes Cytogenetics and cell genetics Medium 2055111
2024 Microbial metabolite indole-3-carboxaldehyde (3-IAld) activates the Aryl hydrocarbon Receptor (AhR), which promotes Tph1 expression in mast cells in peripheral lymph nodes, leading to mast-cell serotonin production; this AhR-mast cell-Tph1 axis is proposed as a microbiome-driven tolerogenic mechanism in multiple sclerosis. Ex vivo lymph node assays, AhR pathway analysis, mast cell experiments with 3-IAld and L-kynurenine, serum metabolite correlation with MS disease duration Scientific reports Low 38509264

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proceedings of the National Academy of Sciences of the United States of America 326 14597720
2004 Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland. Biological psychiatry 168 14960297
2020 Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma. Annals of the rheumatic diseases 137 32963045
2004 Association between the TPH gene A218C polymorphism and suicidal behavior: a meta-analysis. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 109 14681922
2022 Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis. Nature communications 102 35831277
2012 SERT and TPH-1 mRNA expression are reduced in irritable bowel syndrome patients regardless of visceral sensitivity state in large intestine. American journal of physiology. Gastrointestinal and liver physiology 83 22323131
2007 Identification and distribution of tryptophan hydroxylase (TPH)-positive neurons in the planarian Dugesia japonica. Neuroscience research 83 17624455
2002 Association of anger-related traits with SNPs in the TPH gene. Molecular psychiatry 81 12399958
2005 A second tryptophan hydroxylase isoform, TPH-2 mRNA, is increased by ovarian steroids in the raphe region of macaques. Brain research. Molecular brain research 77 15857682
2002 The C. elegans POU-domain transcription factor UNC-86 regulates the tph-1 tryptophan hydroxylase gene and neurite outgrowth in specific serotonergic neurons. Development (Cambridge, England) 75 12135927
1991 Localization of human tryptophan hydroxylase (TPH) to chromosome 11p15.3----p14 by in situ hybridization. Cytogenetics and cell genetics 69 2055111
2006 Further clarification of the contribution of the tryptophan hydroxylase (TPH) gene to suicidal behavior using systematic allelic and genotypic meta-analyses. Human genetics 68 16450114
2005 Haplotype analysis reveals tryptophan hydroxylase (TPH) 1 gene variants associated with major depression. Biological psychiatry 65 16165107
1998 Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic factor (CNTF)). Genomics 63 9790747
2005 Temperament and character in mood disorders: influence of DRD4, SERTPR, TPH and MAO-A polymorphisms. Neuropsychobiology 62 16319504
2004 Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 59 15274037
2003 Gene-environment interaction in psychiatric disorders as indicated by season of birth variations in tryptophan hydroxylase (TPH), serotonin transporter (5-HTTLPR) and dopamine receptor (DRD4) gene polymorphisms. Psychiatry research 58 12860364
2003 Deliberate self-harm is associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms in five other serotonergic genes. Psychological medicine 58 12877392
2001 TPH and suicidal behavior: a study in suicide completers. Molecular psychiatry 57 11244493
2022 Berberine ameliorates depression-like behavior in CUMS mice by activating TPH1 and inhibiting IDO1-associated with tryptophan metabolism. Phytotherapy research : PTR 53 36089660
2002 Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders. American journal of medical genetics 51 11992558
2018 Association between single nucleotide polymorphisms of TPH1 and TPH2 genes, and depressive disorders. Journal of cellular and molecular medicine 49 29314569
2011 Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 49 21308753
2012 Gene therapy by targeted adenovirus-mediated knockdown of pulmonary endothelial Tph1 attenuates hypoxia-induced pulmonary hypertension. Molecular therapy : the journal of the American Society of Gene Therapy 48 22525513
2011 Association of variations in TPH1 and HTR2B with gestational weight gain and measures of obesity. Obesity (Silver Spring, Md.) 48 21836641
2008 Stress upregulates TPH1 but not TPH2 mRNA in the rat dorsal raphe nucleus: identification of two TPH2 mRNA splice variants. Cellular and molecular neurobiology 46 18197473
2007 Role of TPH-2 in brain function: news from behavioral and pharmacologic studies. Journal of neuroscience research 45 17492791
2018 BDNF mediates the protective effects of scopolamine in reserpine-induced depression-like behaviors via up-regulation of 5-HTT and TPH1. Psychiatry research 41 30529315
2008 TPH2 and TPH1: association of variants and interactions with heroin addiction. Behavior genetics 41 18181017
2011 Anxiety-like behaviors and expression of SERT and TPH in the dorsal raphé of estrogen- and fluoxetine-treated ovariectomized rats. Pharmacology, biochemistry, and behavior 40 21382399
2000 TPH gene may be associated with suicidal behavior, but not with schizophrenia in the Korean population. Human heredity 40 10899755
2010 The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 39 19526457
2012 Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms. Journal of affective disorders 38 22483952
2008 Posttranslational regulation of TPH1 is responsible for the nightly surge of 5-HT output in the rat pineal gland. Journal of pineal research 38 18705647
2014 Tryptophan hydroxylase 1 (Tph-1)-targeted bone anabolic agents for osteoporosis. Journal of medicinal chemistry 37 24844139
1994 Early induction of rat brain tryptophan hydroxylase (TPH) mRNA following parachlorophenylalanine (PCPA) treatment. Brain research. Molecular brain research 37 8015380
2000 Identification and analysis of new sequence variants in the human tryptophan hydroxylase (TpH) gene. Molecular psychiatry 34 10673768
2008 Molecular cloning, characterization and expression of two tryptophan hydroxylase (TPH-1 and TPH-2) genes in the hypothalamus of Atlantic croaker: down-regulation after chronic exposure to hypoxia. Neuroscience 33 19015006
2001 Influence of 5-HTTLPR and TPH variants on illness time course in mood disorders. Journal of psychiatric research 33 11578639
2020 Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease. Modern rheumatology 32 32023137
2014 Association of TPH-1 and TPH-2 gene polymorphisms with suicidal behavior: a systematic review and meta-analysis. BMC psychiatry 32 25005534
2012 Selective estrogen receptor-beta (SERM-beta) compounds modulate raphe nuclei tryptophan hydroxylase-1 (TPH-1) mRNA expression and cause antidepressant-like effects in the forced swim test. Neuropharmacology 32 22796107
2007 Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach. BMC psychiatry 32 17521439
2022 Peptide OM-LV20 protects astrocytes against oxidative stress via the 'PAC1R/JNK/TPH1' axis. The Journal of biological chemistry 31 36037970
2008 No association of TPH1 218A/C polymorphism with treatment response and intolerance to SSRIs in Japanese patients with major depression. Neuropsychobiology 31 18332644
2020 Poricoic acid A as a modulator of TPH-1 expression inhibits renal fibrosis via modulating protein stability of β-catenin and β-catenin-mediated transcription. Therapeutic advances in chronic disease 30 33062239
2007 Regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) receptors in the human stomach and duodenum. Neurogastroenterology and motility 30 17509016
2005 Pleiotropic effect of the TPH A779C polymorphism on nicotine dependence and personality. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 30 15635702
2013 Identification of a functional TPH1 polymorphism associated with irritable bowel syndrome bowel habit subtypes. The American journal of gastroenterology 29 24060757
2002 Involvement of NF-Y and Sp1 in basal and cAMP-stimulated transcriptional activation of the tryptophan hydroxylase (TPH ) gene in the pineal gland. Journal of neurochemistry 29 12065627
2022 Role of interferons (IFNs) in the differentiation of T peripheral helper (Tph) cells. International immunology 28 35780437
2010 TPH1 is associated with major depressive disorder but not with SSRI/SNRI response in Taiwanese patients. Psychopharmacology 28 20945066
2006 Family-based association study of TPH1 and TPH2 polymorphisms in autism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 28 16958027
2012 TPH1, MAOA, serotonin receptor 2A and 2C genes in citalopram response: possible effect in melancholic and psychotic depression. Neuropsychobiology 27 23221997
2019 Hydrocarbonoclastic Ascomycetes to enhance co-composting of total petroleum hydrocarbon (TPH) contaminated dredged sediments and lignocellulosic matrices. New biotechnology 26 30654133
2008 Increased risk of suicide attempt in mood disorders and TPH1 genotype. Journal of affective disorders 26 18977032
2006 Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia. Human genetics 26 16741719
2018 Serotonin Exhibits Accelerated Bleomycin-Induced Pulmonary Fibrosis through TPH1 Knockout Mouse Experiments. Mediators of inflammation 25 29849496
2013 A neuronal signaling pathway of CaMKII and Gqα regulates experience-dependent transcription of tph-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 23325232
2006 Interaction between TPH1 and GNB3 genotypes and electroconvulsive therapy in major depression. Journal of neural transmission (Vienna, Austria : 1996) 25 17066254
2023 Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells. Communications biology 24 37161050
2022 Tph Cells Expanded in Primary Sjögren's Syndrome. Frontiers in medicine 24 35755031
2019 Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) 24 31721892
2024 Cytotoxic Tph subset with low B-cell helper functions and its involvement in systemic lupus erythematosus. Communications biology 23 38448723
2017 Characterization of mammary-specific disruptions for Tph1 and Lrp5 during murine lactation. Scientific reports 23 29123193
2006 TPH gene polymorphism and aging: indication of combined effect on the predisposition to violent suicide. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 23 16389591
2009 Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1. International clinical psychopharmacology 22 19474754
2005 Polymorphism screening and haplotype analysis of the tryptophan hydroxylase gene (TPH1) and association with bipolar affective disorder in Taiwan. BMC medical genetics 22 15799788
2018 TPH-2 Gene Polymorphism in Major Depressive Disorder Patients With Early-Wakening Symptom. Frontiers in neuroscience 21 30519155
2007 The tryptophan hydroxylase (TPH) 2 gene unlike TPH-1 exhibits no association with stress-induced depression. Journal of affective disorders 21 17692928
2006 Association of TPH1 with suicidal behaviour and psychiatric disorders in the Chinese population. Journal of medical genetics 21 16467214
2006 Tryptophan hydroxylase 1 gene (TPH1) moderates the influence of social support on depressive symptoms in adults. Journal of affective disorders 21 17134762
2021 Expanded circulating peripheral helper T cells in primary biliary cholangitis: Tph cells in PBC. Molecular immunology 20 33446391
2020 [6]-Gingerol Ameliorates Cisplatin-Induced Pica by Regulating the TPH/MAO-A/SERT/5-HT/5-HT3 Receptor System in Rats. Drug design, development and therapy 20 33061309
2015 Association analysis of TPH-1 and TPH-2 genes with suicidal behavior in patients with attempted suicide in Mexican population. Comprehensive psychiatry 20 26028568
2014 Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea-predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPH1. Neurogastroenterology and motility 20 25428414
2007 The role of the TPH1 and TPH2 genes for nicotine dependence: a genetic association study in two different age cohorts. Neuropsychobiology 20 17986837
2024 A microbially produced AhR ligand promotes a Tph1-driven tolerogenic program in multiple sclerosis. Scientific reports 18 38509264
2020 Protein acetylation derepresses Serotonin Synthesis to potentiate Pancreatic Beta-Cell Function through HDAC1-PKA-Tph1 signaling. Theranostics 18 32641996
2022 Identification of T Peripheral Helper (Tph) Cells. Methods in molecular biology (Clifton, N.J.) 17 34802122
2022 Role of interferons (IFNs) in the differentiation of T peripheral helper (Tph) cells. International immunology 17 35723683
2017 Glucose potentiates β-cell function by inducing Tph1 expression in rat islets. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 28794173
2014 Association of COMT and TPH-2 genes with DSM-5 based PTSD symptoms. Journal of affective disorders 17 25451452
2023 TGF-β3 in differentiation and function of Tph-like cells and its relevance to disease activity in patients with systemic lupus erythematosus. Rheumatology (Oxford, England) 16 36370078
2023 A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients. Proceedings of the National Academy of Sciences of the United States of America 16 36669118
2020 Disruption of tph1 genes demonstrates the importance of serotonin in regulating ventilation in larval zebrafish (Danio rerio). Respiratory physiology & neurobiology 16 33271304
2015 TPH, SLC6A2, SLC6A3, DRD2 and DRD4 Polymorphisms and Neuroendocrine Factors Predict SSRIs Treatment Outcome in the Chinese Population with Major Depression. Pharmacopsychiatry 15 25642918
2013 Associations Between Variations in TPH1 , TPH2 and SLC6A4 Genes and Postpartum Depression: A Study in the Jordanian Population. Balkan journal of medical genetics : BJMG 15 24265583
2012 Combined structure-based pharmacophore and 3D-QSAR studies on phenylalanine series compounds as TPH1 inhibitors. International journal of molecular sciences 15 22754301
2010 Common genetic variations in TPH1/TPH2 genes are not associated with schizophrenia in Japanese population. Neuroscience letters 15 20144688
2021 TPH1 and 5-HT7 Receptor Overexpression Leading to Gemcitabine-Resistance Requires Non-Canonical Permissive Action of EZH2 in Pancreatic Ductal Adenocarcinoma. Cancers 13 34771469
2014 [The association of polymorphisms in SLC18A1, TPH1 and RELN genes with risk of paranoid schizophrenia]. Molekuliarnaia biologiia 13 25842846
2010 Association between Serotonin-Related Polymorphisms in 5HT2A, TPH1, TPH2 Genes and Bipolar Disorder in Korean Population. Psychiatry investigation 13 20396435
2010 Tryptophan hydroxylase gene 1 (TPH1) variants associated with cerebrospinal fluid 5-hydroxyindole acetic acid and homovanillic acid concentrations in healthy volunteers. Psychiatry research 13 20580984
2009 Modulation of anger control in suicide attempters by TPH-1. Genes, brain, and behavior 13 19220488
2019 Association of TPH1 and serotonin transporter genotypes with treatment response for suicidal ideation: a preliminary study. European archives of psychiatry and clinical neuroscience 12 30923939
2012 TPH gene polymorphisms are associated with disease perception and quality of life in women with irritable bowel syndrome. Biological research for nursing 12 23172723
2022 T1D patient-derived hematopoietic stem cells are programmed to generate Tph, Tfh, and autoimmunity-associated B cell subsets in human immune system mice. Clinical immunology (Orlando, Fla.) 11 35644520
2021 Kamishoyosan (a Japanese traditional herbal formula), which effectively reduces the aggressive biting behavior of male and female mice, and potential regulation through increase of Tph1, Tph2, and Esr2 mRNA levels. Brain research 11 34260963
2008 Tryptophan hydroxylase gene (TPH1) and peripheral tryptophan levels in depression. Journal of affective disorders 11 18177948

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