Genomes and Genes
Gene Symbol: HTR1A
Description: 5-hydroxytryptamine receptor 1A
Alias: 5-HT-1A, 5-HT1A, 5HT1a, ADRB2RL1, ADRBRL1, G-21, PFMCD, 5-hydroxytryptamine receptor 1A, 5-HT1a receptor, 5-hydroxytryptamine (serotonin) receptor 1A, G protein-coupled, guanine nucleotide-binding regulatory protein-coupled receptor
- Kobilka B, Frielle T, Collins S, Yang Feng T, Kobilka T, Francke U, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature. 1987;329:75-9 pubmed..Like the beta 2-adrenergic receptor this gene appears to be intronless, containing an uninterrupted long open reading frame which encodes a putative protein with all the expected structural features of a G-protein-coupled receptor. ..
- Hettema J, An S, van den Oord E, Neale M, Kendler K, Chen X. Association study between the serotonin 1A receptor (HTR1A) gene and neuroticism, major depression, and anxiety disorders. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:661-6 pubmed publisher..In this study, we examined the serotonin 1A receptor gene, HTR1A, for its association with shared genetic risk across a range of anxiety and depression-related phenotypes...
- Frey B, Rosa Neto P, Lubarsky S, Diksic M. Correlation between serotonin synthesis and 5-HT1A receptor binding in the living human brain: a combined alpha-[11C]MT and [18F]MPPF positron emission tomography study. Neuroimage. 2008;42:850-7 pubmed publisher..The combination of [(18)F]MPPF and alpha-[(11)C]MT PET offers a means to investigate key determinants of 5-HT neurotransmission under physiological and psychopathological conditions in the human brain in vivo. ..
- Hadjighassem M, Austin M, Szewczyk B, Daigle M, Stockmeier C, Albert P. Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression. Biol Psychiatry. 2009;66:214-22 pubmed publisher..Human Freud-2 binds to the 5-HT1A DRE and represses the human 5-HT1A receptor gene to regulate its expression in non-serotonergic cells and neurons. ..
- Czesak M, Lemonde S, Peterson E, Rogaeva A, Albert P. Cell-specific repressor or enhancer activities of Deaf-1 at a serotonin 1A receptor gene polymorphism. J Neurosci. 2006;26:1864-71 pubmed..Cell-specific regulation by Deaf-1 could underlie region-specific alterations in 5-HT1A receptor expression in different mood disorders. ..
- Domschke K, Braun M, Ohrmann P, Suslow T, Kugel H, Bauer J, et al. Association of the functional -1019C/G 5-HT1A polymorphism with prefrontal cortex and amygdala activation measured with 3 T fMRI in panic disorder. Int J Neuropsychopharmacol. 2006;9:349-55 pubmed..These serotonergic polymorphisms might increase the risk for panic disorder by contributing to an altered processing of emotional stimuli. ..
- Lesch K, Gutknecht L. Focus on The 5-HT1A receptor: emerging role of a gene regulatory variant in psychopathology and pharmacogenetics. Int J Neuropsychopharmacol. 2004;7:381-5 pubmed
- Chen T, Yu Y, Hong C, Chen M, Tsai S. Association analysis for the C-1019G promoter variant of the 5-HT1A receptor gene with auditory evoked potentials in major depression. Neuropsychobiology. 2004;50:292-5 pubmed..Further studies with other genetic polymorphisms in the serotonergic system may help to clarify the relation between serotonergic function and AEP components. ..
- Huang Y, Battistuzzi C, Oquendo M, Harkavy Friedman J, Greenhill L, Zalsman G, et al. Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology. Int J Neuropsychopharmacol. 2004;7:441-51 pubmedDysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants...
- Lemonde S, Turecki G, Bakish D, Du L, Hrdina P, Bown C, et al. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci. 2003;23:8788-99 pubmed..We suggest a novel transcriptional model in which the G(-1019) allele derepresses 5-HT1A autoreceptor expression to reduce serotonergic neurotransmission, predisposing to depression and suicide. ..
- Nishiguchi N, Shirakawa O, Ono H, Nishimura A, Nushida H, Ueno Y, et al. Lack of an association between 5-HT1A receptor gene structural polymorphisms and suicide victims. Am J Med Genet. 2002;114:423-5 pubmed..These findings suggest that neither of these two polymorphisms is associated with suicide victims and it is unlikely that the 5-HT1A receptor gene is implicated in the susceptibility to suicide. ..
- Albert P, Le François B, Millar A. Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness. Mol Brain. 2011;4:21 pubmed publisher..Extensive characterization of the transcriptional regulation of the 5-HT1A gene (HTR1A) using cell culture systems has revealed a GC-rich "housekeeping" promoter that non-selectively drives ..
- Kishi T, Tsunoka T, Ikeda M, Kawashima K, Okochi T, Kitajima T, et al. Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis. J Hum Genet. 2009;54:629-33 pubmed publisherSeveral genetic studies have shown an association between the 5-HT1A receptor gene (HTR1A) and major depressive disorder (MDD); however, results have been rather inconsistent...
- Hong C, Chen T, Yu Y, Tsai S. Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder. Pharmacogenomics J. 2006;6:27-33 pubmed..The firing rate of dorsal raphe serotonergic neurons is controlled by somatodendritic 5-hydroxytryptamine 1A (HTR1A) autoreceptors, and desensitization of these receptors is implicated in the antidepressant mechanism of selective ..
- Lindstedt F, Karshikoff B, Schalling M, Olgart Hoglund C, Ingvar M, Lekander M, et al. Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception. PLoS ONE. 2012;7:e43221 pubmed publisher..Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity...
- Parks C, Shenk T. The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. J Biol Chem. 1996;271:4417-30 pubmed..This initiator sequence differs from previously characterized initiators and may represent a new class of this transcriptional control sequence. ..
- Anttila S, Huuhka K, Huuhka M, Rontu R, Hurme M, Leinonen E, et al. Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression. J Neural Transm (Vienna). 2007;114:1065-8 pubmed..5-HT1A C1019G and BDNF G196A (Val66Met) polymorphisms were studied. The combination of 5-HT1A GG and BDNF GA + AA genotypes is associated with an increased risk of depression. ..
- Le François B, Czesak M, Steubl D, Albert P. Transcriptional regulation at a HTR1A polymorphism associated with mental illness. Neuropharmacology. 2008;55:977-85 pubmed publisher..This review focuses on the C(-1019)G (rs6295) promoter polymorphism of the 5-HT1A receptor gene (HTR1A) and its effect on the activity of transcription factors that recognize the C-allele, including Deaf-1, Hes1 and ..
- Aune T, McGrath K, Sarr T, Bombara M, Kelley K. Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine. J Immunol. 1993;151:1175-83 pubmed..Results presented here characterize the receptor on Jurkat cells as the 5HT1a receptor subtype and show that mitogen-activated but not resting human T cells also express the 5HT1a receptor ..
- Szewczyk B, Albert P, Burns A, Czesak M, Overholser J, Jurjus G, et al. Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder. Int J Neuropsychopharmacol. 2009;12:155-68 pubmed publisher..In addition, the gender-specific alterations in cortical NUDR and 5-HT1A receptor proteins could represent an underlying biological mechanism associated with the higher incidence of depression in women. ..
- Yevtushenko O, Oros M, Reynolds G. Early response to selective serotonin reuptake inhibitors in panic disorder is associated with a functional 5-HT1A receptor gene polymorphism. J Affect Disord. 2010;123:308-11 pubmed publisher..These results indicate the importance of a 5-HT1A receptor gene polymorphism in the response to SSRI treatment of panic disorder. ..
- de Almeida J, Mengod G. Serotonin 1A receptors in human and monkey prefrontal cortex are mainly expressed in pyramidal neurons and in a GABAergic interneuron subpopulation: implications for schizophrenia and its treatment. J Neurochem. 2008;107:488-96 pubmed publisher..The knowledge of the phenotype of the prefrontal cortex (PFC) cells expressing 5-HT(1A) will help understanding serotonin actions in PFC. ..
- Fargin A, Raymond J, Lohse M, Kobilka B, Caron M, Lefkowitz R. The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature. 1988;335:358-60 pubmed..We now report that the protein product of the genomic clone, G21, transiently expressed in monkey kidney cells has all the typical ligand-binding characteristics of the 5-hydroxytryptamine (5-HT1A) receptor. ..
- Stockmeier C, Shapiro L, Dilley G, Kolli T, Friedman L, Rajkowska G. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci. 1998;18:7394-401 pubmed
- Neumeister A, Bain E, Nugent A, Carson R, Bonne O, Luckenbaugh D, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24:589-91 pubmed..These results provide for the first time in vivo evidence for the involvement of 5-HT(1A)Rs in the pathophysiology of PD. ..
- Rothe C, Gutknecht L, Freitag C, Tauber R, Mossner R, Franke P, et al. Association of a functional 1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia. Int J Neuropsychopharmacol. 2004;7:189-92 pubmed..03, n=101). In conclusion, our findings do not support a major contribution of this polymorphism to the pathogenesis of panic disorder, but provide evidence for a possible role in the subgroup with agoraphobia. ..
- Koller G, Bondy B, Preuss U, Zill P, Soyka M. The C(-1019)G 5-HT1A promoter polymorphism and personality traits: no evidence for significant association in alcoholic patients. Behav Brain Funct. 2006;2:7 pubmedThe 5HT1A receptor is one of at least 14 different receptors for serotonin which has a role in moderating several brain functions and may be involved in the aetiology of several psychiatric disorders...
- David S, Murthy N, Rabiner E, Munafo M, Johnstone E, Jacob R, et al. A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J Neurosci. 2005;25:2586-90 pubmed..The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states. ..
- Kato M, Fukuda T, Wakeno M, Okugawa G, Takekita Y, Watanabe S, et al. Effect of 5-HT1A gene polymorphisms on antidepressant response in major depressive disorder. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:115-23 pubmed publisher..Rs6295C/G SNP in the 5-HT1A gene (HTR1A) has been found to affect the expression and function of HTR1A...
- Drago A, Ronchi D, Serretti A. 5-HT1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Int J Neuropsychopharmacol. 2008;11:701-21 pubmed..This lack of consistency can be also due to an incomplete gene investigation. To make progress on this point, a list of validated single nucleotide polymorphisms (SNPs) covering the whole gene is proposed for further investigations. ..
- Moses Kolko E, Wisner K, Price J, Berga S, Drevets W, Hanusa B, et al. Serotonin 1A receptor reductions in postpartum depression: a positron emission tomography study. Fertil Steril. 2008;89:685-92 pubmedTo measure brain serotonin-1A (5HT1A) receptor binding potential (BP) in healthy and depressed postpartum women. 5HT1A receptor BP was measured with positron emission tomography by using [(11)C]WAY100635 a single time...
- Choi W, Lee B, Yang J, Kim Y. Association Study between 5-HT1A Receptor Gene C(-1019)G Polymorphism and Panic Disorder in a Korean Population. Psychiatry Investig. 2010;7:141-6 pubmed publisher..This result suggests that the serotonin 1A receptor and serotonin may play a role in the pathogenesis of panic disorder. ..
- Mickey B, Ducci F, Hodgkinson C, Langenecker S, Goldman D, Zubieta J. Monoamine oxidase A genotype predicts human serotonin 1A receptor availability in vivo. J Neurosci. 2008;28:11354-9 pubmed publisher..These results demonstrate a sex-specific interaction between two key molecules of the human serotonergic system, and suggest a neurobiological basis for sexual dimorphism in serotonin-modulated phenotypes. ..
- Fakra E, Hyde L, Gorka A, Fisher P, Munoz K, Kimak M, et al. Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. Arch Gen Psychiatry. 2009;66:33-40 pubmed publisher..A common functional variation (C[-1019]G) in the human 5-HT(1A) gene (HTR1A) represents 1 potential source of such interindividual variability...
- Szewczyk B, Albert P, Rogaeva A, Fitzgibbon H, May W, Rajkowska G, et al. Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression. Int J Neuropsychopharmacol. 2010;13:1089-101 pubmed publisher..These data may also suggest that reductions in Freud-1 protein expression in the PFC may be associated with early onset of MDD. ..
- Strobel A, Gutknecht L, Rothe C, Reif A, Mossner R, Zeng Y, et al. Allelic variation in 5-HT1A receptor expression is associated with anxiety- and depression-related personality traits. J Neural Transm (Vienna). 2003;110:1445-53 pubmed..In the present study, we evaluated the role of the HTR1A-1019 polymorphism in the modulation of individual differences in personality traits by an association study of a ..
- Sullivan G, Ogden R, Oquendo M, Kumar J, Simpson N, Huang Y, et al. Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression. Biol Psychiatry. 2009;66:223-30 pubmed publisher..The raphe effect may be partly genetic. No difference in 5-HT1A BP(F) between BD and control females may reflect greater effect of prior antidepressant exposure in BD females. ..
- Schmitz A, Kirsch P, Reuter M, Alexander N, Kozyra E, Kuepper Y, et al. The 5-HT1A C(-1019)G polymorphism, personality and electrodermal reactivity in a reward/punishment paradigm. Int J Neuropsychopharmacol. 2009;12:383-92 pubmed publisher..These findings demonstrate for the first time that the 5-HT(1A) polymorphism is related to personality on the level of a triadic approach including behaviour, physiology and self-reports. ..
- Neff C, Abkevich V, Packer J, Chen Y, Potter J, Riley R, et al. Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression. Mol Psychiatry. 2009;14:621-30 pubmed publisherThe HTR1A -1019C>G genotype was associated with major depression in the Utah population...
- Parsey R, Arango V, Olvet D, Oquendo M, van Heertum R, John Mann J. Regional heterogeneity of 5-HT1A receptors in human cerebellum as assessed by positron emission tomography. J Cereb Blood Flow Metab. 2005;25:785-93 pubmed..With CW as a reference region, V(3)'' cannot be used to detect differences in 5-HT(1A) receptors between men and women, suggesting the need for arterial input functions to determine BP. ..
- Zetzsche T, Preuss U, Bondy B, Frodl T, Zill P, Schmitt G, et al. 5-HT1A receptor gene C -1019 G polymorphism and amygdala volume in borderline personality disorder. Genes Brain Behav. 2008;7:306-13 pubmed publisher..Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder. ..
- Malaguti A, Rossini D, Lucca A, Magri L, Lorenzi C, Pirovano A, et al. Role of COMT, 5-HT(1A) , and SERT genetic polymorphisms on antidepressant response to Transcranial Magnetic Stimulation. Depress Anxiety. 2011;28:568-73 pubmed publisher..The effect of COMT and SERTPR did not reach statistical significance. The analysis of these and other candidate genes in larger samples could help explain genetic influence on TMS response. ..
- Kraus M, Al Taie O, Schäfer A, Pfersdorff M, Lesch K, Scheurlen M. Serotonin-1A receptor gene HTR1A variation predicts interferon-induced depression in chronic hepatitis C. Gastroenterology. 2007;132:1279-86 pubmed..All patients were genotyped for functional variations in the 5-HT(1A) receptor (HTR1A), 5-HT transporter (SLC6A4, 5-HTT), and tryptophan hydoxylase-2 (TPH2)...
- Kishi T, Yoshimura R, Fukuo Y, Okochi T, Matsunaga S, Umene Nakano W, et al. The serotonin 1A receptor gene confer susceptibility to mood disorders: results from an extended meta-analysis of patients with major depression and bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2013;263:105-18 pubmed publisherThe serotonin 1A receptor gene (HTR1A) has been associated with mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP)...
- Parsey R, Oquendo M, Ogden R, Olvet D, Simpson N, Huang Y, et al. Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry. 2006;59:106-13 pubmed..AE appears to have long-term effects on 5-HT(1A). ..
- Lambe E, Fillman S, Webster M, Shannon Weickert C. Serotonin receptor expression in human prefrontal cortex: balancing excitation and inhibition across postnatal development. PLoS ONE. 2011;6:e22799 pubmed publisher..from across postnatal life, we investigated the expression of key serotonin receptors with distinct inhibitory (HTR1A, HTR5A) and excitatory (HTR2A, HTR2C, HTR4, HTR6) effects on cortical neurons, including two receptors which ..
- Gupta K, Kotian A, Subramanian H, Daniell H, Ali H. Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties. Oncotarget. 2015;6:28573-87 pubmed publisher..Low cost production of AMPs in plants should facilitate their advancement to the clinic overcoming major hurdles in current production systems. ..
- Dong X, Herrera Hernández M, Ramon E, Garriga P. Docosahexaenoic acid phospholipid differentially modulates the conformation of G90V and N55K rhodopsin mutants associated with retinitis pigmentosa. Biochim Biophys Acta Biomembr. 2017;1859:975-981 pubmed publisher..The results emphasize the distinct role of DHA on different phenotypic rhodopsin mutations associated with classical (G90V) and sector (N55K) retinitis pigmentosa. ..
- Kautzky A, James G, Philippe C, Baldinger Melich P, Kraus C, Kranz G, et al. The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning. Transl Psychiatry. 2017;7:e1150 pubmed publisher..The common polymorphism rs6295 of the serotonin-1A receptor gene (HTR1A) is affecting the transcriptional regulation of the 5-HT1A receptor and has been closely linked to MDD...
- Mastrangelo L, Cassidy A, Mulholland F, Wang W, Bao Y. Serotonin receptors, novel targets of sulforaphane identified by proteomic analysis in Caco-2 cells. Cancer Res. 2008;68:5487-91 pubmed publisher..Thus, the effect of sulforaphane may help to elucidate signaling pathways serotonin-mediated in colon cancer and lead to development of potential novel therapeutic agents. ..
- Zhou X, Geng L, Wang D, Yi H, Talmon G, Wang J. R-Spondin1/LGR5 Activates TGFβ Signaling and Suppresses Colon Cancer Metastasis. Cancer Res. 2017;77:6589-6602 pubmed publisher..Our study uncovers a novel cross-talk between LGR5 and TGFβ signaling in colon cancer and identifies LGR5 as a new modulator of TGFβ signaling able to suppress colon cancer metastasis. Cancer Res; 77(23); 6589-602. ©2017 AACR. ..
- Vlot A, de Witte W, Danhof M, van der Graaf P, van Westen G, de Lange E. Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling. AAPS J. 2017;20:11 pubmed publisher..The presented integrative structure-pharmacokinetic-pharmacodynamic modeling provides an improved understanding of tissue and target selectivity. ..
- Yoon H, Radulovic M, Walters G, Paulsen A, Drucker K, Starski P, et al. Protease activated receptor 2 controls myelin development, resiliency and repair. Glia. 2017;65:2070-2086 pubmed publisher..These findings suggest that PAR2 is an important controller of myelin production and regeneration, both in the developing and adult spinal cord. ..
- Iceta R, Mesonero J, Aramayona J, Alcalde A. Expression of 5-HT1A and 5-HT7 receptors in Caco-2 cells and their role in the regulation of serotonin transporter activity. J Physiol Pharmacol. 2009;60:157-64 pubmed..However, in both cases, the desensitization did not show itself to be mediated by a reduction of the amount of receptors in the membrane. ..