THAP1

Summary

Gene Symbol: THAP1
Description: THAP domain containing 1
Alias: DYT6, THAP domain-containing protein 1, 4833431A01Rik, THAP domain containing, apoptosis associated protein 1, THAP domain protein 1, nuclear proapoptotic factor
Species: human

Top Publications

  1. doi Clinical and genetic evaluation of DYT1 and DYT6 primary dystonia in China
    F B Cheng
    Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China
    Eur J Neurol 18:497-503. 2011
  2. doi Mutation screening of the DYT6/THAP1 gene in Italy
    Monica Bonetti
    IRCCS Casa Sollievo della Sofferenza, CSS Mendel Institute, Rome, Italy
    Mov Disord 24:2424-7. 2009
  3. pmc THAP proteins target specific DNA sites through bipartite recognition of adjacent major and minor grooves
    Alex Sabogal
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA
    Nat Struct Mol Biol 17:117-23. 2010
  4. pmc Novel THAP1 sequence variants in primary dystonia
    J Xiao
    Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Neurology 74:229-38. 2010
  5. pmc Structural determinants of specific DNA-recognition by the THAP zinc finger
    Sébastien Campagne
    CNRS, Institut de Pharmacologie et de Biologie Structurale and Université de Toulouse, UPS, F 31077 Toulouse, France
    Nucleic Acids Res 38:3466-76. 2010
  6. pmc The THAP-zinc finger protein THAP1 associates with coactivator HCF-1 and O-GlcNAc transferase: a link between DYT6 and DYT3 dystonias
    Raoul Mazars
    CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne, F 31077 Toulouse, France
    J Biol Chem 285:13364-71. 2010
  7. pmc THAP1 mutations (DYT6) are an additional cause of early-onset dystonia
    H Houlden
    University College London Institute of Neurology, Queen Square, London WC1N 3BG, England
    Neurology 74:846-50. 2010
  8. doi Prevalence of THAP1 sequence variants in German patients with primary dystonia
    Anne S Söhn
    Department of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Tubingen, Germany
    Mov Disord 25:1982-6. 2010
  9. doi DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation
    Justus L Groen
    Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Mov Disord 25:2420-7. 2010
  10. ncbi The THAP domain: a novel protein motif with similarity to the DNA-binding domain of P element transposase
    Myriam Roussigne
    Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse, France
    Trends Biochem Sci 28:66-9. 2003

Research Grants

  1. Laurie J Ozelius; Fiscal Year: 2016
  2. The Role of THAP1 in Dystonia
    Mark S Ledoux; Fiscal Year: 2013
  3. Signature-based chemical screening for DYT6 dystonia
    DAVID CRISTOPHER BRAGG; Fiscal Year: 2012
  4. Gene discovery in primary dystonia using whole exome sequencing
    Laurie J Ozelius; Fiscal Year: 2013
  5. Molecular Regulation of a Striatal DARPP-32 Phenotype
    Michelle Ehrlich; Fiscal Year: 2008
  6. Huntington's Disease and the Striatum
    Michelle E Ehrlich; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications86

  1. doi Clinical and genetic evaluation of DYT1 and DYT6 primary dystonia in China
    F B Cheng
    Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China
    Eur J Neurol 18:497-503. 2011
    ..DYT1 is caused by a mutation in the TOR1A gene, whilst mutations in THAP1 gene have been identified as responsible for DYT6...
  2. doi Mutation screening of the DYT6/THAP1 gene in Italy
    Monica Bonetti
    IRCCS Casa Sollievo della Sofferenza, CSS Mendel Institute, Rome, Italy
    Mov Disord 24:2424-7. 2009
    Mutations in the THAP1 gene on chromosome 8p21-p22 (DYT6 locus) have been recently reported as causative of autosomal dominant primary torsion dystonia (PTD) in four Amish-Mennonite families and in 12 additional probands of different ..
  3. pmc THAP proteins target specific DNA sites through bipartite recognition of adjacent major and minor grooves
    Alex Sabogal
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA
    Nat Struct Mol Biol 17:117-23. 2010
    ..Sequence analysis of natural and in vitro-selected binding sites suggests that several THAPs (DmTHAP and human THAP1 and THAP9) recognize a bipartite TXXGGGX(A/T) consensus motif; homology suggests THAP proteins bind DNA through a ..
  4. pmc Novel THAP1 sequence variants in primary dystonia
    J Xiao
    Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Neurology 74:229-38. 2010
    b>THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites...
  5. pmc Structural determinants of specific DNA-recognition by the THAP zinc finger
    Sébastien Campagne
    CNRS, Institut de Pharmacologie et de Biologie Structurale and Université de Toulouse, UPS, F 31077 Toulouse, France
    Nucleic Acids Res 38:3466-76. 2010
    Human THAP1 is the prototype of a large family of cellular factors sharing an original THAP zinc-finger motif responsible for DNA binding...
  6. pmc The THAP-zinc finger protein THAP1 associates with coactivator HCF-1 and O-GlcNAc transferase: a link between DYT6 and DYT3 dystonias
    Raoul Mazars
    CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne, F 31077 Toulouse, France
    J Biol Chem 285:13364-71. 2010
    b>THAP1 is a sequence-specific DNA binding factor that regulates cell proliferation through modulation of target genes such as the cell cycle-specific gene RRM1...
  7. pmc THAP1 mutations (DYT6) are an additional cause of early-onset dystonia
    H Houlden
    University College London Institute of Neurology, Queen Square, London WC1N 3BG, England
    Neurology 74:846-50. 2010
    The clinical phenotype of DYT6 consists mainly of primary craniocervical dystonia. Recently, the THAP1 gene was identified as the cause of DYT6, where a total of 13 mutations have been identified in Amish-Mennonite and European families.
  8. doi Prevalence of THAP1 sequence variants in German patients with primary dystonia
    Anne S Söhn
    Department of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Tubingen, Germany
    Mov Disord 25:1982-6. 2010
    ..Only recently, mutations in THAP1 have been shown to be the cause of DYT6 dystonia...
  9. doi DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation
    Justus L Groen
    Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Mov Disord 25:2420-7. 2010
    Mutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been associated with DYT6 dystonia...
  10. ncbi The THAP domain: a novel protein motif with similarity to the DNA-binding domain of P element transposase
    Myriam Roussigne
    Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse, France
    Trends Biochem Sci 28:66-9. 2003
    ..Our results suggest that the THAP domain is a novel example of a DBD that is shared between cellular proteins and transposases from mobile genomic parasites...
  11. pmc Direct interaction between causative genes of DYT1 and DYT6 primary dystonia
    Sophie Gavarini
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
    Ann Neurol 68:549-53. 2010
    ..TOR1A(DYT1) and the transcription factor THAP1(DYT6) are the only genes identified thus far for primary dystonia...
  12. doi Screening of Brazilian families with primary dystonia reveals a novel THAP1 mutation and a de novo TOR1A GAG deletion
    Patricia de Carvalho Aguiar
    Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil
    Mov Disord 25:2854-7. 2010
    The TOR1A and THAP1 genes were screened for mutations in a cohort of 21 Brazilian patients with Primary torsion dystonia (PTD)...
  13. doi Homozygous THAP1 mutations as cause of early-onset generalized dystonia
    Susanne A Schneider
    Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lubeck, Lubeck, Germany
    Mov Disord 26:858-61. 2011
    ..This revealed 2 candidate regions including the THAP1 gene, where heterozygous mutations cause dystonia 6. A homozygous missense mutation in THAP1 (c.95T>A; p...
  14. pmc An African-American family with dystonia
    Andreas Puschmann
    Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Parkinsonism Relat Disord 17:547-50. 2011
    ..Recently, mutations in Thanatos-associated protein domain containing, apoptosis associated protein 1 (THAP1) have been described in DYT6 dystonia and associated with some cases of familial and sporadic late-onset dystonia ..
  15. doi DYT6 dystonia: review of the literature and creation of the UMD Locus-Specific Database (LSDB) for mutations in the THAP1 gene
    Arnaud Blanchard
    INSERM U827, Montpellier, F 34000, France
    Hum Mutat 32:1213-24. 2011
    By family-based screening, first Fuchs and then many other authors showed that mutations in THAP1 (THAP [thanatos-associated protein] domain-containing, apoptosis-associated protein 1) account for a substantial proportion of familial, ..
  16. doi THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression
    Fu Bo Cheng
    Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Wangfujing Street, Beijing, 100075, People s Republic of China
    J Neurol 259:342-7. 2012
    Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations...
  17. pmc Identification and functional analysis of novel THAP1 mutations
    Katja Lohmann
    Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lubeck, Lubeck, Germany
    Eur J Hum Genet 20:171-5. 2012
    Mutations in THAP1 have been associated with dystonia 6 (DYT6). THAP1 encodes a transcription factor that represses the expression of DYT1...
  18. pmc Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and description of new cases
    Mark S Ledoux
    Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Link Building Suite 415, Memphis, TN 38163, USA
    Parkinsonism Relat Disord 18:414-25. 2012
    An extensive variety of THAP1 sequence variants have been associated with focal, segmental and generalized dystonia with age of onset ranging from 3 to over 60 years...
  19. ncbi THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies
    Myriam Roussigne
    Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse, France
    Oncogene 22:2432-42. 2003
    ..Here, we report that THAP1 is a novel nuclear proapoptotic factor associated with PML NBs, which potentiates both serum withdrawal- and TNF alpha-induced apoptosis, and ..
  20. pmc The THAP domain of THAP1 is a large C2CH module with zinc-dependent sequence-specific DNA-binding activity
    Thomas Clouaire
    Laboratoire de Biologie Vasculaire, Equipe Labellisée La Ligue 2003, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5089, 205 route de Narbonne, 31077 Toulouse, France
    Proc Natl Acad Sci U S A 102:6907-12. 2005
    ..approximately 100 distinct THAP proteins in model animal organisms, including human nuclear proapoptotic factors THAP1 and DAP4/THAP0, transcriptional repressor THAP7, zebrafish orthologue of cell cycle regulator E2F6, and ..
  21. doi Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study
    Ana Djarmati
    Schilling Department of Clinical and Molecular Neurogenetics, University of Lubeck, Lubeck, Germany
    Lancet Neurol 8:447-52. 2009
    ..Recently, two mutations in THAP1, the gene that encodes THAP (thanatos-associated protein) domain-containing apoptosis-associated protein 1 (THAP1),..
  22. pmc Mutations in THAP1 (DYT6) in early-onset dystonia: a genetic screening study
    Susan B Bressman
    Department of Neurology, Beth Israel Medical Center, New York, NY 10003, USA
    Lancet Neurol 8:441-6. 2009
    Mutations in THAP1 were recently identified as the cause of DYT6 primary dystonia; a founder mutation was detected in Amish-Mennonite families, and a different mutation was identified in another family of European descent...
  23. doi Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia
    Tania Fuchs
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Genet 41:286-8. 2009
    We report the discovery of a mutation in the THAP1 gene in three Amish-Mennonite families with mixed-onset primary torsion dystonia (also known as DYT6 dystonia)...
  24. ncbi Structure-function analysis of the THAP zinc finger of THAP1, a large C2CH DNA-binding module linked to Rb/E2F pathways
    Damien Bessière
    University of Toulouse, Institute of Pharmacology and Structural Biology, France
    J Biol Chem 283:4352-63. 2008
    b>THAP1, the founding member of a previously uncharacterized large family of cellular proteins (THAP proteins), is a sequence-specific DNA-binding factor that has recently been shown to regulate cell proliferation through modulation of pRb/..
  25. ncbi The THAP-zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes
    Corinne Cayrol
    Laboratoire de Biologie Vasculaire, Equipe Labellisée La Ligue 2006, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique Unite Mixte de Recherche, Toulouse, France
    Blood 109:584-94. 2007
    We recently cloned a novel human nuclear factor (designated THAP1) from postcapillary venule endothelial cells (ECs) that contains a DNA-binding THAP domain, shared with zebrafish E2F6 and several Caenorhabditis elegans proteins ..
  26. doi Lack of association between TOR1A and THAP1 mutations and sporadic adult-onset primary focal dystonia in a Chinese population
    Lei Wang
    Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025 China Laboratory of Neurodegenerative Diseases and Key Laboratory of Stem Cell Biology, Institute of Health Science, Shanghai Institutes for Biological Sciences SIBS, Chinese Academy of Sciences CAS and Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Clin Neurol Neurosurg 142:26-30. 2016
    TOR1A (torsin family 1, member A) and THAP1 (THAP domain containing, apoptosis associated protein 1) are two candidate genes that have been reported to be linked to adult-onset primary dystonia...
  27. pmc Role of Gα(olf) in familial and sporadic adult-onset primary dystonia
    Satya R Vemula
    Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Hum Mol Genet 22:2510-9. 2013
    ..After excluding mutations in known primary dystonia genes (TOR1A, THAP1 and CIZ1), whole-exome sequencing identified a GNAL missense mutation (c.682G>T, p...
  28. pmc Genetic issues in the diagnosis of dystonias
    Simona Petrucci
    Neurogenetics Unit, CSS Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo, Italy Department of Experimental Medicine, Sapienza University of Rome Rome, Italy
    Front Neurol 4:34. 2013
    ..in a monogenic fashion, and many genes and loci have been identified for autosomal dominant (DYT1/TOR1A; DYT6/THAP1; DYT4/TUBB4a; DYT7; DYT13; DYT21; DYT23/CIZ1; DYT24/ANO3; DYT25/GNAL) and recessive (DYT2; DYT17) forms...
  29. pmc Early registration of diffusion tensor images for group tractography of dystonia patients
    An Vo
    Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA
    J Magn Reson Imaging 37:67-75. 2013
    ..We propose using an early registration method that produces sharper group images and enables us to do group tractography...
  30. pmc SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia
    Matt Baker
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
    Neurogenetics 15:23-30. 2014
    ..precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia-related gene THAP1. The deletion co-segregated with disease in all family members...
  31. doi Genetics in dystonia
    Christine Klein
    Institute of Neurogenetics, University of Lubeck, Lubeck, Germany Electronic address
    Parkinsonism Relat Disord 20:S137-42. 2014
    ..Confirmed genes for isolated dystonias include TOR1A/DYT1; THAP1/DYT6; GNAL/DYT25...
  32. doi Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia
    Fu Bo Cheng
    Department of Medical Genetics, University of Tuebingen, 72076, Germany Department of Neurology, The First Hospital of Jilin University, Changchun, PR China
    Mov Disord 29:1079-83. 2014
    ..The ΔGAG deletion of the TOR1A gene (DYT1) is responsible for DYT1 dystonia. However, no other TOR1A mutation has been reported in the Chinese population...
  33. doi THAP1, the gene mutated in DYT6 dystonia, autoregulates its own expression
    Alev Erogullari
    Sektion für Funktionelle Genetik am Institut für Humangenetik, University of Luebeck, Luebeck 23538, Germany
    Biochim Biophys Acta 1839:1196-204. 2014
    b>THAP1 encodes a transcription factor but its regulation is largely elusive. TOR1A was shown to be repressed by THAP1 in vitro. Notably, mutations in both of these genes lead to dystonia (DYT6 or DYT1)...
  34. doi DYT6 Dystonia: A Neuropathological Study
    Reema Paudel
    Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
    Neurodegener Dis 16:273-8. 2016
    Mutations in the thanatos-associated protein domain containing apoptosis-associated protein 1 gene (THAP1) are responsible for adult-onset isolated dystonia (DYT6)...
  35. pmc Inherited isolated dystonia: clinical genetics and gene function
    William Dauer
    Department of Neurology, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, 48109 220, USA
    Neurotherapeutics 11:807-16. 2014
    ..Here, I review the clinical genetics and cell biology of three forms of inherited dystonia for which the causative mutation is known: DYT1 (TOR1A), DYT6 (THAP1), DYT25 (GNAL).
  36. pmc SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype
    Kathryn J Peall
    MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK
    J Neurol 261:2296-304. 2014
    ..In those where no mutation was found, DYT1 (GAG deletion), GCH1, THAP1 and NKX2.1 genes were also sequenced. Nineteen (21.3%) probands had an SGCE mutation...
  37. pmc Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia
    Marta Ruiz
    Department of Pediatrics
    Hum Mol Genet 24:7159-70. 2015
    DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant...
  38. pmc Recessive mutations in the α3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia
    Michael Zech
    Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, 81675 Munich, Germany Department of Neurology and Neurological Sciences and Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA Institut für Humangenetik, Helmholtz Zentrum Munchen, 85764 Munich, Germany
    Am J Hum Genet 96:883-93. 2015
    ..Although autosomal-dominant mutations in TOR1A, THAP1, and GNAL have been found in some cases, the molecular mechanisms underlying isolated dystonia are largely unknown...
  39. pmc Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions
    Ewa Golanska
    Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland
    PLoS ONE 10:e0129656. 2015
    ..We sequenced THAP1 exons 1, 2 and 3 including exon-intron boundaries and 5'UTR fragment in 96 non-DYT1 dystonia patients...
  40. doi Bufalin alters gene expressions associated DNA damage, cell cycle, and apoptosis in human lung cancer NCI-H460 cells in vitro
    Shin Hwar Wu
    Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan
    Molecules 19:6047-57. 2014
    ..About 165 apoptosis-related genes were affected. CASP9 was up-regulated by 5.51 fold and THAP1 by 2.75-fold while CCAR1 was down-regulated by 2.24 fold. 107 genes related to DNA damage/repair were affected...
  41. ncbi [Dystonia genes and elucidation of their roles in dystonia pathogenesis]
    Toshitaka Kawarai
    Department of Clinical Neuroscience Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima
    Rinsho Shinkeigaku 53:419-29. 2013
    ..It has been reported that effects of deep brain stimulation can vary significantly depending on genotype. Accumulation of genotype-outcome correlations would contribute to treatment decisions for dystonia patients...
  42. doi A novel long non-coding RNA T-ALL-R-LncR1 knockdown and Par-4 cooperate to induce cellular apoptosis in T-cell acute lymphoblastic leukemia cells
    Lin Zhang
    Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Leuk Lymphoma 55:1373-82. 2014
    ..Further studies revealed that T-ALL-R-LncR1 knockdown facilitated the formation of a Par-4/THAP1 protein complex, resulting in the activation of caspase-3 and an increase of pro-apoptotic Smac protein in T-ALL ..
  43. pmc Dystonia type 6 gene product Thap1: identification of a 50 kDa DNA-binding species in neuronal nuclear fractions
    Maitane Ortiz-Virumbrales
    Acta Neuropathol Commun 2:139. 2014
    Mutations in THAP1 result in dystonia type 6, with partial penetrance and variable phenotype...
  44. pmc Heterogeneity in primary dystonia: lessons from THAP1, GNAL, and TOR1A in Amish-Mennonites
    Rachel Saunders-Pullman
    Department of Neurology, Beth Israel Medical Center, New York, New York, USA Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA
    Mov Disord 29:812-8. 2014
    A founder mutation in the Thanatos-associated (THAP) domain containing, apoptosis associated protein 1 (THAP1) gene causing primary dystonia was originally described in the Amish-Mennonites...
  45. doi Genetics of dystonia: what's known? What's new? What's next?
    Katja Lohmann
    Institute of Neurogenetics, University of Luebeck, Luebeck, Germany
    Mov Disord 28:899-905. 2013
    ..Isolated dystonia can be caused by mutations in TOR1A (DYT1), TUBB4 (DYT4), THAP1 (DYT6), CIZ1 (DYT23), ANO3 (DYT24), and GNAL (DYT25)...
  46. pmc THAP1 mutations and dystonia phenotypes: genotype phenotype correlations
    Georgia Xiromerisiou
    Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, London, United Kingdom Department of Neurology, Faculty of Medicine University of Thessaly, Larissa, Greece
    Mov Disord 27:1290-4. 2012
    b>THAP1 mutations have been shown to be the cause of DYT6...
  47. pmc Neuropathology of cervical dystonia
    C N Prudente
    Dept of Neurology, Emory University, Atlanta, GA 30322, USA
    Exp Neurol 241:95-104. 2013
    ..investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD...
  48. pmc Neural expression of the transcription factor THAP1 during development in rat
    Y Zhao
    Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Neuroscience 231:282-95. 2013
    Loss of function mutations in THAP1 has been associated with primary generalized and focal dystonia in children and adults...
  49. pmc The genetics of dystonias
    Mark S Ledoux
    Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA
    Adv Genet 79:35-85. 2012
    ..Many cases of childhood- and adolescent-onset dystonia are due to mutations in TOR1A and THAP1. Mutations in THAP1 and CIZ1 have been associated with sporadic and familial adult-onset dystonia...
  50. doi Review: genetics and neuropathology of primary pure dystonia
    R Paudel
    Department of Molecular Neuroscience Queen Square Brain Bank and UCL Institute of Neurology, London, UK
    Neuropathol Appl Neurobiol 38:520-34. 2012
    ..TOR1A) gene responsible for DYT1 and the thanatos-associated domain-containing apoptosis-associated protein 1 (THAP1) gene responsible for DYT6, have important implications in understanding these two entities and also for other ..
  51. pmc Towards the classification of DYT6 dystonia mutants in the DNA-binding domain of THAP1
    Sébastien Campagne
    CNRS IPBS Institut de Pharmacologie et de Biologie Structurale 205 route de Narbonne, BP64182, F 31077 Toulouse, France
    Nucleic Acids Res 40:9927-40. 2012
    The transcription factor THAP1 (THanatos Associated Protein 1) has emerged recently as the cause of DYT6 primary dystonia, a type of rare, familial and mostly early-onset syndrome that leads to involuntary muscle contractions...
  52. doi Mutation screening of the DYT6/THAP1 gene in Serbian patients with primary dystonia
    Valerija S Dobričić
    Institute of Neurology CCS, School of Medicine, University of Belgrade, Dr Subotica 6, 11000 Belgrade, Serbia
    J Neurol 260:1037-42. 2013
    ..Besides DYT1/TOR1A gene, DYT6/THAP1 gene is the second gene known to cause primary pure dystonia...
  53. pmc Mutations in GNAL cause primary torsion dystonia
    Tania Fuchs
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA
    Nat Genet 45:88-92. 2013
    ..Only three genes for primary torsion dystonia (PTD), TOR1A (DYT1), THAP1 (DYT6) and CIZ1 (ref. 5), have been identified...
  54. pmc SGCE mutations cause psychiatric disorders: clinical and genetic characterization
    Kathryn J Peall
    MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Henry Wellcome Building, Heath Park, Cardiff, UK
    Brain 136:294-303. 2013
    ..In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced...
  55. pmc Par-4/THAP1 complex and Notch3 competitively regulated pre-mRNA splicing of CCAR1 and affected inversely the survival of T-cell acute lymphoblastic leukemia cells
    C Lu
    Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
    Oncogene 32:5602-13. 2013
    ..Here, we report that the cooperative synergy between prostate apoptosis response factor-4 (Par-4) and THAP1 induces cell cycle and apoptosis regulator 1 (CCAR1) gene expression and cellular apoptosis in human T-ALL cell ..
  56. doi Incentive loss and hippocampal gene expression in inbred Roman high- (RHA-I) and Roman low- (RLA-I) avoidance rats
    Marta Sabariego
    Department of Psychology, University of Jaen, Spain Electronic address
    Behav Brain Res 257:62-70. 2013
    ..analysis of these hippocampi showed that four differentially-expressed, and qRT-PCR-validated genes (TAAR2, THAP1, PKD2L1, NANOS), have relevance for brain function and behavior, including schizophrenia, depression, anxiety, and ..
  57. doi Subcellular distribution of THAP1 and alterations in the microstructure of brain white matter in DYT6 dystonia
    Fu Bo Cheng
    Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Wangfujing Street, Beijing, PR China
    Parkinsonism Relat Disord 18:978-82. 2012
    Mutations in the THAP1 gene have recently been identified as the cause of DYT6 primary dystonia. However, the changes in THAP1 gene function and in the microstructure of brain white matter have not been well-characterized.
  58. doi Common polymorphisms in dystonia-linked genes and susceptibility to the sporadic primary dystonias
    Jeremy R B Newman
    Clinical Neuroscience Group, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Don Young Road, Nathan, Queensland, Australia
    Parkinsonism Relat Disord 18:351-7. 2012
    ..To date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1, have been assessed...
  59. doi [Monogenetic dystonia: revisiting the dopaminergic hypothesis]
    A Blanchard
    INSERM, U827, Institut Universitaire de Recherche Clinique, 641, avenue du Doyen Gaston Giraud, 34093 Montpellier Cedex 05, France UFR médecine, Universite de Montpellier 1, 34000 Montpellier, France
    Rev Neurol (Paris) 166:389-99. 2010
    ..The recent identification of mutations in the gene THAP1 in DYT6 dystonia reopens the very interesting question of the in fine involvement of dopamine in the different ..
  60. doi [Genetics of dystonia]
    C Kamm
    Universitat Rostock, Klinik und Poliklinik fur Neurologie, Gehlsheimer Strasse 20, Rostock
    Fortschr Neurol Psychiatr 77:S32-6. 2009
    ..Other genes which have only recently been identified include: THAP1, causing adolescent-onset primary dystonia of mixed type (DYT6); ATP1A3, responsible for Rapid-Onset Dystonia-..
  61. doi The monogenic primary dystonias
    Ulrich Muller
    Institut fur Humangenetik, Justus Liebig Universitat, Schlangenzahl 14, 35392 Giessen, Germany
    Brain 132:2005-25. 2009
    ..The disease gene has been identified in 10 primary dystonias, seven autosomal dominant (TOR1A/DYT1, GCH1/DYT5a, THAP1/DYT6, PNKD1/MR-1/DYT8, SGCE/DYT11, ATP1A3/DYT12 and SLC2A1/DYT18), two autosomal recessive (TH/DYT5b and PRKRA/..
  62. doi Genetics and treatment of dystonia
    Cordelia S Schwarz
    Department of Neurology, Beth Israel Medical Center, Phillips Ambulatory Care Center, New York, NY 10003, USA
    Neurol Clin 27:697-718, vi. 2009
    ..that protects against clinical expression in DYT1 dystonia and the identification of the gene causing DYT6, THAP1. The authors review genetic etiologies and discuss phenotypes as well as counseling of patients regarding ..
  63. pmc Abnormal striatal and thalamic dopamine neurotransmission: Genotype-related features of dystonia
    M Carbon
    Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, NY 11030, USA
    Neurology 72:2097-103. 2009
    ..To determine whether changes in D(2) receptor availability are present in carriers of genetic mutations for primary dystonia...
  64. ncbi What's new in dystonia?
    Vicki Shanker
    Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY 10003, USA
    Curr Neurol Neurosci Rep 9:278-84. 2009
    ..of a genetic modifier that protects against clinical expression in DYT1 and the identification of the DYT6 gene (THAP1). Several reports provided expanded descriptions of the clinical features of dystonia and its associated symptoms...
  65. doi Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia families
    Simone Zittel
    Department of Neurology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Mov Disord 25:2405-12. 2010
    ..and electrophysiological characteristics as well as laryngoscopical and transcranial ultrasound (TCS) findings in THAP1 mutation carriers (MutC)...
  66. ncbi Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the Amish-Mennonites
    Rachel Saunders-Pullman
    Department of Neurology, Beth Israel Medical Center, New York, New York 10003, USA
    Am J Med Genet A 143:2098-105. 2007
    The DYT6 gene for primary torsion dystonia (PTD) was mapped to chromosome 8p21-q22 in two Amish-Mennonite families who shared a haplotype of marker alleles across a 40 cM linked region...
  67. doi The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6)
    Frank J Kaiser
    Institute of Human Genetics, University of Lubeck, Lubeck, Germany
    Ann Neurol 68:554-9. 2010
    Mutations in THAP1 have been associated with dystonia 6. THAP1 encodes a transcription factor with mostly unknown targets. We tested the hypothesis that THAP1 regulates the expression of DYT1 (TOR1A), another dystonia-causing gene...
  68. pmc Spasmodic dysphonia: a laryngeal control disorder specific to speech
    Christy L Ludlow
    Department of Communication Sciences and Disorders, James Madison University, Harrisonburg, Virginia 22807, USA
    J Neurosci 31:793-7. 2011
    ..A few cases with single mutations in THAP1, a gene involved in transcription regulation, suggest that a weak genetic predisposition may contribute to ..
  69. pmc The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystonia
    Jianfeng Xiao
    Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Mov Disord 26:549-52. 2011
    Sequence variants in coding and noncoding regions of THAP1 have been associated with primary dystonia.
  70. ncbi Neuroimaging in human dystonia
    Kotaro Asanuma
    Center for Neurosciences, Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, NY 11030, and Department of Neurology, North Shore University Hospital, New York, NY, USA
    J Med Invest 52:272-9. 2005
    ..This presentation will focus on an integrated approach to understanding the pathophysiology of this genetic and biochemically diverse disorder...
  71. pmc Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain
    Cem Sengel
    Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurochem 118:1087-100. 2011
    Thanatos-associated [THAP] domain-containing apoptosis-associated protein 1 (THAP1) is a DNA-binding protein that has been recently associated with DYT6 dystonia, a hereditary movement disorder involving sustained, involuntary muscle ..
  72. ncbi Regional metabolism in primary torsion dystonia: effects of penetrance and genotype
    M Carbon
    Center for Neurosciences, North Shore Long Island Jewish Research Institute, Manhasset, NY 11030, USA
    Neurology 62:1384-90. 2004
    ..The authors have previously used [18F]fluorodeoxyglucose (FDG) PET to identify a reproducible pattern of regional glucose metabolism that was expressed in both manifesting and nonmanifesting carriers of the DYT1 primary dystonia mutation...
  73. doi Novel THAP1 gene mutations in patients with primary dystonia from southwest China
    Wei Song
    Department of Neurology, West China Hospital, Sichuan University, Chengdu Sichuan, China
    J Neurol Sci 309:63-7. 2011
    Clinical presentation and DYT6/THAP1 mutations among Chinese patients with primary dystonia have not been well studied.
  74. doi Pallidal deep brain stimulation for DYT6 dystonia
    Fedor Panov
    Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York, USA
    J Neurol Neurosurg Psychiatry 83:182-7. 2012
    Mutations of the THAP1 gene were recently shown to underlie DYT6 torsion dystonia. Little is known about the response of this dystonia subtype to deep brain stimulation (DBS) at the internal globus pallidus (GPi).
  75. doi Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal
    Robert A Wilcox
    Neurology Department, Flinders Medical Centre, Adelaide, SA, Australia
    Mov Disord 26:2404-8. 2011
    ..analysis was performed to DYT1, DYT6, DYT7, DYT11, DYT13, DYT15, and ATP7B with microsatellite markers and the THAP1 (DYT6), PRKRA (DYT16), and ATP7B (WND) genes were sequenced...
  76. doi Overview of primary monogenic dystonia
    Marianna Spatola
    Department of Clinical Neuroscience, Centre Hospitalier Universitaire Vaudois CHUV UNIL, Lausanne, Switzerland
    Parkinsonism Relat Disord 18:S158-61. 2012
    ..DYT1 is caused by a GAG deletion in the TOR1A gene. Mutations in the THAP1 gene cause DYT6, a form of pure dystonia that primarily involves cranio-cervical and upper limb muscles...
  77. ncbi Idiopathic torsion dystonia linked to chromosome 8 in two Mennonite families
    L Almasy
    Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
    Ann Neurol 42:670-3. 1997
    ..We mapped a locus (DYT6) associated with prominent cranial-cervical ITD in two large Mennonite families to chromosome 8...

Research Grants6

  1. Laurie J Ozelius; Fiscal Year: 2016
    ..GNAL, encoding G?olf, in patients with early onset torsion dystonia (EOTD) who do not harbor mutations in TOR1A or THAP1. G?olf is a G protein that couples striatal dopamine D1 (D1R) and adenosine A2a (A2AR) receptors to adenylyl ..
  2. The Role of THAP1 in Dystonia
    Mark S Ledoux; Fiscal Year: 2013
    ..Recently, a mutation in the gene THAP1 was identified as the cause of DTY6 dystonia in Amish-Mennonites...
  3. Signature-based chemical screening for DYT6 dystonia
    DAVID CRISTOPHER BRAGG; Fiscal Year: 2012
    ..The causative gene was recently identified as THAP1 which encodes a DNA binding protein, THAP1 (thanatos-associated protein [THAP] domain-containing apoptosis-..
  4. Gene discovery in primary dystonia using whole exome sequencing
    Laurie J Ozelius; Fiscal Year: 2013
    ..There are eight PTD loci assigned (DYT1, 2, 4, 6, 7, 13, 17 and 21), but only two of the genes (TOR1A-DYT1 and THAP1-DYT6) have been isolated...
  5. Molecular Regulation of a Striatal DARPP-32 Phenotype
    Michelle Ehrlich; Fiscal Year: 2008
    ....
  6. Huntington's Disease and the Striatum
    Michelle E Ehrlich; Fiscal Year: 2010
    ..Knowledge of striatal-specific transcriptional regulation will also be highly relevant to other diseases of the basal ganglia in which transcriptional dysregulation plays a role. II. ..