Affinage

THAP1

THAP domain-containing protein 1 · UniProt Q9NVV9

Length
213 aa
Mass
24.9 kDa
Annotated
2026-04-28
83 papers in source corpus 25 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

THAP1 is a nuclear zinc-finger transcription factor that uses its N-terminal C2CH THAP domain to recognize specific DNA sequences in target gene promoters and recruits cofactors HCF-1 and OGT to regulate cell-cycle progression, proteasome homeostasis, DNA double-strand break repair pathway choice, myelination, and zygotic genome activation (PMID:15863623, PMID:20200153, PMID:17003378, PMID:39952963, PMID:33857404, PMID:28697333, PMID:41731150). THAP1 directly activates or represses key target genes—including RRM1, TOR1A, PSMB5, SHLD1, GusB, and SOD2—and autoregulates its own promoter; it homodimerizes through a C-terminal coiled-coil domain and cooperates with transcription factors YY1 and SP1/SP4 to control broader transcriptional programs, particularly in oligodendrocytes where it governs myelination timing through glycosaminoglycan catabolism and YY1 DNA occupancy (PMID:25088175, PMID:34312226, PMID:34686877, PMID:35015830). Loss of THAP1-mediated PSMB5 transcription impairs proteasome assembly and proteostasis (PMID:39929834). Mutations in THAP1 cause DYT6 primary torsion dystonia through diverse mechanisms including impaired DNA binding, reduced protein thermostability, disrupted nuclear localization, and failure to assemble active transcription complexes with partner factors (PMID:19182804, PMID:22844099, PMID:34686877).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Before THAP1's DNA-binding or transcriptional functions were known, its localization to PML nuclear bodies and interaction with Par-4 established it as a nuclear factor with proapoptotic activity, raising the question of how its THAP domain contributes to function.

    Evidence Co-IP, immunofluorescence, and apoptosis assays in mammalian cells

    PMID:12717420

    Open questions at the time
    • Mechanism by which THAP1 potentiates apoptosis beyond Par-4 interaction was not defined
    • Whether THAP domain contributed via DNA binding was unknown
  2. 2005 High

    The THAP domain was established as a zinc-dependent, sequence-specific DNA-binding module recognizing an 11-nucleotide consensus, resolving whether THAP1 is a bona fide transcription factor.

    Evidence SELEX, site-directed mutagenesis of C2CH residues, zinc chelation assay in vitro

    PMID:15863623

    Open questions at the time
    • No endogenous genomic targets identified yet
    • No in vivo binding demonstrated
  3. 2006 High

    Identification of RRM1 as a direct in vivo transcriptional target via ChIP demonstrated that THAP1 functions as a cell-cycle regulator controlling pRB/E2F target genes and G1/S progression in endothelial cells.

    Evidence ChIP, microarray profiling, RNAi, and retroviral overexpression in endothelial cells

    PMID:17003378

    Open questions at the time
    • Cofactors mediating transcriptional regulation were unknown
    • Whether cell-cycle role extends beyond endothelial cells was untested
  4. 2007 High

    NMR structure of the THAP zinc finger revealed its unique fold—an antiparallel β-sheet with a loop-helix-loop insertion—and mapped the DNA-contact surface, providing the structural basis for understanding pathogenic mutations.

    Evidence Multidimensional NMR, alanine scanning mutagenesis

    PMID:18073205

    Open questions at the time
    • No structure of THAP domain bound to DNA
    • Full-length THAP1 structure not determined
  5. 2009 Medium

    Genetic linkage of THAP1 mutations to DYT6 primary torsion dystonia, combined with demonstration that the causative missense mutation impairs DNA binding, established THAP1 as a dystonia gene and transcriptional dysregulation as a disease mechanism.

    Evidence Family-based genetic mapping followed by DNA-binding assay of mutant protein

    PMID:19182804

    Open questions at the time
    • Only one mutation tested functionally
    • Neural cell-type-specific consequences were unexplored
    • Whether all DYT6 mutations impair DNA binding was unknown
  6. 2010 High

    Two advances resolved THAP1's cofactor recruitment and a disease-relevant target: (1) THAP1 recruits HCF-1 and OGT via a conserved HBM motif to activate RRM1, and (2) THAP1 directly binds and represses the TOR1A promoter, linking two dystonia genes in a common pathway.

    Evidence Mass spectrometry, Co-IP, ChIP, RNAi (for HCF-1/OGT); EMSA, ChIP-qPCR, luciferase assays (for TOR1A), replicated across two labs

    PMID:20200153 PMID:20865765 PMID:20976771

    Open questions at the time
    • Whether HCF-1 is required at all THAP1 target promoters was unknown
    • Functional consequence of TOR1A derepression in neurons not tested
  7. 2011 Medium

    Mapping of the homodimerization domain to a C-terminal coiled-coil (residues 154–166) established that THAP1 functions as a dimer, while showing that most DYT6 coiled-coil mutations do not disrupt dimerization, pointing to other pathogenic mechanisms.

    Evidence Co-IP with domain deletions and systematic mutant analysis

    PMID:21752024

    Open questions at the time
    • Functional significance of dimerization for transcriptional activity was not tested
    • Single-lab Co-IP without reciprocal pull-down for some mutants
  8. 2012 High

    Biophysical analysis of DYT6 THAP-domain mutations revealed that reduced protein thermostability—not uniformly abolished DNA binding—is a major pathogenic mechanism, with some mutants unfolding below 37°C.

    Evidence NMR, DSF, ITC, fluorescence spectroscopy on multiple disease mutants

    PMID:22844099

    Open questions at the time
    • Whether reduced stability translates to reduced protein levels in patient neurons was not shown
    • No in vivo validation of thermostability model
  9. 2014 Medium

    Discovery of THAP1 autoregulation—binding its own promoter to repress transcription—explained how DYT6 mutations cause elevated THAP1 levels, establishing a negative feedback loop disrupted in disease.

    Evidence ChIP, luciferase reporters, RT-qPCR, proteasome inhibitor experiments

    PMID:25088175

    Open questions at the time
    • Autoregulatory dynamics not measured in neuronal cells
    • Whether proteasomal degradation of excess THAP1 is a primary clearance mechanism in vivo was not confirmed
  10. 2017 High

    Conditional knockout in mouse CNS revealed that THAP1 is essential for oligodendrocyte maturation and myelination timing, acting cell-autonomously to facilitate YY1 DNA occupancy at OL maturation gene promoters—providing the first neural cell-type-specific mechanism for DYT6 dystonia.

    Evidence Conditional KO mouse, purified OL progenitor assays, ChIP for YY1

    PMID:28697333

    Open questions at the time
    • How THAP1 promotes YY1 binding mechanistically was not resolved
    • Whether myelination defects are the primary cause of dystonia motor phenotype was unclear
  11. 2021 High

    Two new direct THAP1 target pathways were uncovered: (1) GusB regulation controls GAG catabolism in OPCs, with GAG accumulation autoinhibiting maturation (rescuable by β-glucuronidase), and (2) SHLD1 regulation with YY1/HCF1 controls DNA DSB repair pathway choice, conferring PARP inhibitor resistance upon THAP1 loss.

    Evidence ChIP, conditional KO rescue with exogenous enzymes/viral overexpression (GusB); ChIP, genetic epistasis, PARP inhibitor sensitivity assays (SHLD1)

    PMID:33857404 PMID:34312226

    Open questions at the time
    • Whether SHLD1 dysregulation contributes to dystonia pathology is unknown
    • GAG catabolism pathway not validated in human OPCs
  12. 2022 High

    The DYT6 F81L knockin mouse showed that this mutation does not abolish THAP1 DNA binding but instead prevents YY1 recruitment, establishing that failure to organize an active transcription complex—not loss of DNA binding per se—is a distinct pathogenic mechanism.

    Evidence Knockin mouse, ChIP for THAP1 and YY1, myelination assays

    PMID:34686877

    Open questions at the time
    • Structural basis for how F81L disrupts YY1 recruitment is unknown
    • Whether this mechanism applies to other THAP domain mutations is untested
  13. 2022 Medium

    Epigenomic profiling across patient cortex, iPSC-neurons, and KO models revealed that THAP1 directly targets only a minority of dysregulated genes; broader transcriptional effects are mediated indirectly through SP1 and SP4, expanding the model from direct target regulation to a hierarchical transcription factor network.

    Evidence ChIP-seq and RNA-seq across patient tissue, iPSC-derived neurons, rat KO, and cell lines

    PMID:35015830

    Open questions at the time
    • SP1/SP4 regulation by THAP1 not shown to be direct at all loci
    • Cell-type specificity of indirect effects not fully delineated
  14. 2025 High

    THAP1 was identified as a direct transcriptional regulator of PSMB5, and its loss causes defective proteasome assembly and impaired proteostasis—establishing proteasome homeostasis as a fundamental THAP1-dependent process, validated by deep mutational scanning of the entire protein.

    Evidence Genome-wide genetic screen, ChIP, proteasome activity assays, deep mutational scanning, PSMB5 rescue, replicated across two independent studies

    PMID:39929834 PMID:39952963

    Open questions at the time
    • Whether proteostasis defects contribute to DYT6 neuronal dysfunction is unknown
    • Relative importance of PSMB5 versus other targets in disease not established
  15. 2025 High

    THAP1 was discovered to function as a maternal-effect factor activating Rrm1 in oocytes; its loss causes zygotic genome activation failure and 1–2-cell arrest, rescuable by Rrm1 overexpression, revealing an unexpected role in the earliest stages of embryonic development.

    Evidence Oocyte-specific conditional KO, ZGA assays, low-input metabolomics, Rrm1 rescue

    PMID:41731150

    Open questions at the time
    • Whether THAP1 maternal function is relevant to human fertility is unknown
    • Full set of THAP1 maternal targets beyond Rrm1 not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of THAP1-mediated YY1 and HCF-1 co-recruitment, the relative contribution of myelination versus neuronal transcriptional defects to DYT6 dystonia, and whether proteasome homeostasis dysfunction is a primary driver of disease pathology.
  • No co-crystal or cryo-EM structure of THAP1 with any partner or DNA
  • Causal hierarchy among THAP1 target pathways in dystonia neurons not established
  • Full-length THAP1 structure including coiled-coil domain not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
HCF1OGTPAWRSP1SP4YY1
Complex memberships
THAP1 homodimerTHAP1–HCF-1–OGT complexTHAP1–Par-4 complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 The THAP domain of THAP1 is a zinc-dependent sequence-specific DNA-binding domain belonging to the zinc-finger superfamily. In vitro binding-site selection identified an 11-nucleotide consensus DNA-binding sequence recognized by the THAP domain. Site-directed mutagenesis of the C2CH motif cysteines and histidine abolished DNA binding, and zinc chelation with 1,10-o-phenanthroline confirmed zinc dependency. Four conserved residues (P, W, F, P) were also required for DNA binding. In vitro binding-site selection (SELEX), site-directed mutagenesis, zinc chelation assay Proceedings of the National Academy of Sciences of the United States of America High 15863623
2003 THAP1 localizes to PML nuclear bodies and interacts with the proapoptotic protein Par-4. THAP1 potentiates serum withdrawal- and TNF-alpha-induced apoptosis. The THAP domain is not required for Par-4 binding or PML NB localization but is essential for THAP1 proapoptotic activity. Subcellular localization by immunofluorescence, Co-immunoprecipitation, functional apoptosis assays, domain deletion analysis Oncogene High 12717420
2006 THAP1 regulates endothelial cell proliferation and G1/S cell-cycle progression by coordinated repression of pRB/E2F cell-cycle target genes. Chromatin immunoprecipitation showed endogenous THAP1 binds a consensus THAP1-binding site in the RRM1 promoter in vivo, establishing RRM1 as a direct transcriptional target. Both overexpression and RNAi silencing of THAP1 inhibit EC proliferation, indicating an optimal expression range is required. Retroviral gene transfer, RNA interference, microarray expression profiling, chromatin immunoprecipitation (ChIP) Blood High 17003378
2007 NMR structure of the THAP zinc finger of THAP1 revealed an atypical ~80-residue zinc finger with a short antiparallel beta-sheet and a long loop-helix-loop insertion between C2CH zinc-coordinating residues. Alanine scanning mutagenesis and NMR chemical shift perturbation mapped the DNA-binding interface to a highly positively charged surface with multiple lysine and arginine residues. Multidimensional NMR spectroscopy, deletion mutagenesis, alanine scanning mutagenesis, NMR chemical shift perturbation analysis The Journal of biological chemistry High 18073205
2009 A missense mutation in THAP1 found in DYT6 primary torsion dystonia families impairs DNA binding of the THAP domain, suggesting transcriptional dysregulation contributes to the disease phenotype. Genetic identification followed by DNA binding assay demonstrating functional impairment of mutant THAP1 Nature genetics Medium 19182804
2010 THAP1 binds directly to the core promoter of TOR1A (DYT1) and represses its expression. Dystonia-6-associated mutant THAP1 shows decreased repression of TOR1A compared to wild-type. This was demonstrated by electrophoretic mobility shift assay (EMSA) and ChIP-qPCR. Electromobility shift assay (EMSA), chromatin immunoprecipitation quantitative PCR (ChIP-qPCR), luciferase reporter assays Annals of neurology High 20865765 20976771
2010 THAP1 associates with the transcriptional coactivator HCF-1 and O-GlcNAc transferase (OGT) in vivo through a conserved HCF-1-binding motif (HBM). THAP1 mediates recruitment of HCF-1 to the RRM1 promoter during endothelial cell proliferation, and HCF-1 is essential for transcriptional activation of RRM1. Proteomic analysis (mass spectrometry), in vitro binding, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), RNA interference The Journal of biological chemistry High 20200153
2011 THAP1 self-associates (dimerizes) through a region within its C-terminal coiled-coil domain, specifically residues 154–166 containing leucine-zipper-like elements. The DYT6 frameshift mutation Q154fs180X, which removes most of the coiled-coil domain, abolishes self-association, whereas other disease mutations within the coiled-coil (C54Y, F81L, ΔF132, T142A, I149T, A166T) do not disrupt dimerization. Co-immunoprecipitation, domain deletion and truncation analysis Journal of neurochemistry Medium 21752024
2012 NMR, fluorescence, DSF, and ITC analyses of DYT6 missense mutations within the THAP DNA-binding domain showed that mutations do not uniformly abolish DNA binding; some mutants bind DNA stronger than wild-type. However, some mutations alter DNA-binding specificity and most dramatically reduce protein thermostability (unfolding temperatures below 37°C for some mutants vs. 46°C for wild-type), suggesting reduced folded protein population under physiological conditions contributes to disease. NMR spectroscopy, fluorescence spectroscopy, differential scanning fluorimetry (DSF), isothermal titration calorimetry (ITC) Nucleic acids research High 22844099
2014 THAP1 autoregulates its own expression by binding to its own promoter and repressing transcription. Using luciferase reporter assays and quantitative ChIP, the THAP1 minimal promoter was mapped to a 480 bp fragment. DYT6-causing mutations disrupt this autoregulation, leading to elevated THAP1 levels. Overexpressed THAP1 is degraded via the proteasome. Luciferase reporter gene assays, quantitative ChIP, RT-qPCR, proteasome inhibitor experiments Biochimica et biophysica acta Medium 25088175
2013 Par-4 and THAP1 form a protein complex through interaction of their carboxyl termini. THAP1 binds the CCAR1 promoter through its N-terminal zinc-dependent DNA-binding domain. The Par-4/THAP1 complex activates CCAR1 promoter and induces apoptosis. Additionally, Par-4/THAP1 and Notch3 competitively bind the CCAR1 promoter and competitively regulate alternative pre-mRNA splicing of CCAR1 via splicing factors SRp40 and SRp55. Co-immunoprecipitation, luciferase reporter assay, ChIP, splicing assay, domain deletion analysis Oncogene Medium 23975424
2017 THAP1 is essential for timing myelination initiation during CNS maturation through a cell-autonomous role in the oligodendrocyte (OL) lineage. Conditional deletion of THAP1 in the CNS retards OL maturation, delays myelination, and causes persistent motor deficits. Loss of THAP1 disrupts core OL maturation genes and reduces DNA occupancy of YY1, a transcription factor required for OL maturation. Conditional knockout mouse model, OL progenitor cell purification and developmental assays, ChIP for YY1 Developmental cell High 28697333
2017 The coiled-coil domain of THAP1 spanning residues 139–185 is responsible for homodimerization, confirmed by yeast-two-hybrid, GST pull-down, and cross-linking assays. Nine reported DYT6-causing missense mutations within this region do not impair dimerization. Yeast-two-hybrid, GST pull-down, formaldehyde cross-linking assay Journal of molecular neuroscience Medium 28299530
2021 THAP1 modulates extracellular matrix (ECM) composition in oligodendrocyte progenitor cells (OPCs) by regulating glycosaminoglycan (GAG) catabolism. THAP1 directly binds to and regulates the GusB gene encoding β-glucuronidase, a lysosomal GAG-catabolic enzyme. Loss of THAP1 causes OPCs to accumulate and secrete excess GAGs, inhibiting maturation through an autoinhibitory mechanism. Applying GAG-degrading enzymes or overexpressing β-glucuronidase rescues Thap1-/- OL maturation deficits in vitro and in vivo. ChIP, loss-of-function mouse model, rescue experiments with exogenous enzymes and viral overexpression Proceedings of the National Academy of Sciences of the United States of America High 34312226
2021 THAP1, YY1, and HCF1 bind directly to the SHLD1 (Shieldin component) promoter and cooperatively maintain low basal expression of SHLD1, thereby controlling the balance between end protection and resection during DNA double-strand break repair. Loss of THAP1 alters SHLD1 expression and confers resistance to PARP inhibitors and cisplatin in BRCA1-deficient cells. ChIP, promoter binding assays, genetic epistasis in cell lines and mouse models, PARP inhibitor sensitivity assays Molecular cell High 33857404
2022 The DYT6 missense mutation F81L (THAP1F81L) impairs THAP1 transcriptional activity and disrupts CNS myelination. THAP1F81L exhibits normal DNA binding but causes significantly reduced DNA binding of its transcriptional partner YY1, indicating that the mutation disrupts assembly of an active transcription complex rather than directly abolishing DNA binding. Knockin mouse model, ChIP for YY1 DNA occupancy, myelination assays, in vitro transcriptional activity assays Human molecular genetics High 34686877
2022 THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members SP1 and SP4 in a cell-type-dependent manner, as revealed by epigenomic and transcriptomic analyses in patient frontal cortex, iPSC-derived neurons, heterozygous knockout rat, and knockout cell lines. THAP1 directly targets only a minority of differentially expressed genes; broader transcriptional effects are mediated through SP1/SP4. ChIP-seq, RNA-seq in multiple model systems including patient tissue and iPSC-derived neurons Brain Medium 35015830
2025 THAP1 directly regulates expression of PSMB5 (encoding proteasome subunit β5). Depletion of THAP1 disrupts proteasome assembly, reduces proteasome activity, and causes accumulation of ubiquitinated proteins. This was identified by genome-wide genetic screen and confirmed by ChIP demonstrating direct THAP1 binding to the PSMB5 promoter. Genome-wide genetic screen, ChIP, proteasome activity assays, ubiquitinated protein accumulation assay Nature communications High 39929834 39952963
2025 Deep mutational scanning of THAP1 systematically assessed the function of thousands of single amino acid variants, revealing that PSMB5 insufficiency from THAP1 loss leads to defective proteasome assembly and impaired proteostasis. RNA-seq defined THAP1 transcriptional targets, with PSMB5 as a critical direct target. Deep mutational scanning, RNA-seq, proteasome assembly assays, PSMB5 rescue experiments Nature communications High 39929834
2020 ChIP-seq showed THAP1 directly binds the promoter of SOD2 (superoxide dismutase 2). Overexpression of THAP1 increases SOD2 protein, while fibroblasts from THAP1 patients have reduced SOD2 expression. Some THAP1 mutations (C54Y and F81L) decrease THAP1 protein stability, providing an additional pathogenic mechanism of dosage insufficiency. ChIP-seq, microarray transcriptional profiling, western blot in patient fibroblasts Journal of molecular neuroscience Medium 32112337
2011 A DYT6 truncation mutation (Asp191Thrfs*9) that disrupts the nuclear localization signal leads to altered subcellular distribution, with protein detected outside the nucleus, suggesting disrupted nuclear import as a pathogenic mechanism. Subcellular localization by immunofluorescence in transfected cells European journal of human genetics Low 21847143
2012 THAP1 truncation mutations (F22fs71X and F25fs53X) alter subcellular distribution with protein detected in both cytoplasm and nucleus, whereas missense mutations (C54F and L180S) result in predominantly nuclear localization similar to wild-type. Immunofluorescence microscopy and western blot in transfected HEK-293T cells Parkinsonism & related disorders Low 22652465
2014 In mouse neurons, THAP1 exists as multiple protein species including a unique neuronal 50-kDa species that is exclusively nuclear and distinct from the predicted 25-kDa form. This 50-kDa species is found only in brain and testes and is proposed to result from post-translational modification. Western blotting with multiple antibodies, immunoprecipitation, DNA oligonucleotide affinity chromatography, subcellular fractionation Acta neuropathologica communications Medium 25231164
2026 THAP1 functions as a maternal effect factor in mouse oocytes, activating a critical subset of genes including Rrm1 (ribonucleotide reductase). Oocyte-specific deletion of Thap1 causes 1-2-cell arrest and impaired zygotic genome activation. Overexpression of Rrm1 in zygotes almost fully rescues the 2-cell progression and ZGA defects, establishing THAP1→Rrm1→dNTP production as the mechanistic pathway. Oocyte-specific conditional knockout, zygotic genome activation assays, low-input metabolome profiling, Rrm1 overexpression rescue EMBO reports High 41731150

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia. Nature genetics 244 19182804
2009 Mutations in THAP1 (DYT6) in early-onset dystonia: a genetic screening study. The Lancet. Neurology 130 19345147
2005 The THAP domain of THAP1 is a large C2CH module with zinc-dependent sequence-specific DNA-binding activity. Proceedings of the National Academy of Sciences of the United States of America 124 15863623
2003 THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies. Oncogene 123 12717420
2009 Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study. The Lancet. Neurology 116 19345148
2006 The THAP-zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes. Blood 116 17003378
2010 The THAP-zinc finger protein THAP1 associates with coactivator HCF-1 and O-GlcNAc transferase: a link between DYT6 and DYT3 dystonias. The Journal of biological chemistry 91 20200153
2010 Novel THAP1 sequence variants in primary dystonia. Neurology 83 20083799
2010 THAP1 mutations (DYT6) are an additional cause of early-onset dystonia. Neurology 82 20211909
2010 DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation. Movement disorders : official journal of the Movement Disorder Society 75 20687191
2010 The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6). Annals of neurology 75 20976771
2012 Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and description of new cases. Parkinsonism & related disorders 72 22377579
2007 Structure-function analysis of the THAP zinc finger of THAP1, a large C2CH DNA-binding module linked to Rb/E2F pathways. The Journal of biological chemistry 68 18073205
2011 Pallidal deep brain stimulation for DYT6 dystonia. Journal of neurology, neurosurgery, and psychiatry 66 21949105
2010 Direct interaction between causative genes of DYT1 and DYT6 primary dystonia. Annals of neurology 66 20865765
2018 Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions. PLoS genetics 63 29364887
2013 SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia. Neurogenetics 58 24135862
2007 Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the Amish-Mennonites. American journal of medical genetics. Part A 54 17702011
2012 THAP1 mutations and dystonia phenotypes: genotype phenotype correlations. Movement disorders : official journal of the Movement Disorder Society 52 22903657
2011 DYT6 dystonia: review of the literature and creation of the UMD Locus-Specific Database (LSDB) for mutations in the THAP1 gene. Human mutation 50 21793105
2017 The DYT6 Dystonia Protein THAP1 Regulates Myelination within the Oligodendrocyte Lineage. Developmental cell 49 28697333
2015 Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia. Human molecular genetics 47 26376866
2011 Identification and functional analysis of novel THAP1 mutations. European journal of human genetics : EJHG 42 21847143
2009 Mutation screening of the DYT6/THAP1 gene in Italy. Movement disorders : official journal of the Movement Disorder Society 37 19908325
2010 Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia families. Movement disorders : official journal of the Movement Disorder Society 35 20687193
2011 Homozygous THAP1 mutations as cause of early-onset generalized dystonia. Movement disorders : official journal of the Movement Disorder Society 33 21425335
2013 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. Oncogene 31 23975424
2017 THAP1: Role in Mouse Embryonic Stem Cell Survival and Differentiation. Stem cell reports 30 28579396
2015 Long-term effect on dystonia after pallidal deep brain stimulation (DBS) in three members of a family with a THAP1 mutation. Journal of neurology 30 26486352
2014 Heterogeneity in primary dystonia: lessons from THAP1, GNAL, and TOR1A in Amish-Mennonites. Movement disorders : official journal of the Movement Disorder Society 30 24500857
2010 Clinical and genetic evaluation of DYT1 and DYT6 primary dystonia in China. European journal of neurology 30 20825472
2019 Loss of the dystonia gene Thap1 leads to transcriptional deficits that converge on common pathogenic pathways in dystonic syndromes. Human molecular genetics 29 30590536
2014 Deep brain stimulation of the thalamic ventral lateral anterior nucleus for DYT6 dystonia. Stereotactic and functional neurosurgery 29 25359437
2010 Prevalence of THAP1 sequence variants in German patients with primary dystonia. Movement disorders : official journal of the Movement Disorder Society 29 20669277
2011 Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain. Journal of neurochemistry 26 21752024
2021 The dystonia gene THAP1 controls DNA double-strand break repair choice. Molecular cell 24 33857404
2012 Towards the classification of DYT6 dystonia mutants in the DNA-binding domain of THAP1. Nucleic acids research 21 22844099
2012 Neural expression of the transcription factor THAP1 during development in rat. Neuroscience 21 23219941
2021 Dystonia-specific mutations in THAP1 alter transcription of genes associated with neurodevelopment and myelin. American journal of human genetics 20 34672987
2014 THAP1, the gene mutated in DYT6 dystonia, autoregulates its own expression. Biochimica et biophysica acta 20 25088175
2019 The Effect of Globus Pallidus Interna Deep Brain Stimulation on a Dystonia Patient with the GNAL Mutation Compared to Patients with DYT1 and DYT6. Journal of movement disorders 18 31158945
2015 DYT6 Dystonia: A Neuropathological Study. Neuro-degenerative diseases 18 26610312
2014 Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia. Movement disorders : official journal of the Movement Disorder Society 18 24862462
2011 The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystonia. Movement disorders : official journal of the Movement Disorder Society 18 21370264
2010 Screening of Brazilian families with primary dystonia reveals a novel THAP1 mutation and a de novo TOR1A GAG deletion. Movement disorders : official journal of the Movement Disorder Society 18 20925076
2014 A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia. Molecular genetics & genomic medicine 17 24936516
2011 THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression. Journal of neurology 17 21800139
2012 Subcellular distribution of THAP1 and alterations in the microstructure of brain white matter in DYT6 dystonia. Parkinsonism & related disorders 16 22652465
2021 Linking Penetrance and Transcription in DYT-THAP1: Insights From a Human iPSC-Derived Cortical Model. Movement disorders : official journal of the Movement Disorder Society 15 33547842
2021 THAP1 modulates oligodendrocyte maturation by regulating ECM degradation in lysosomes. Proceedings of the National Academy of Sciences of the United States of America 15 34312226
2020 Unraveling Molecular Mechanisms of THAP1 Missense Mutations in DYT6 Dystonia. Journal of molecular neuroscience : MN 15 32112337
2012 Mutation screening of the DYT6/THAP1 gene in Serbian patients with primary dystonia. Journal of neurology 13 23180184
2022 A pathogenic DYT-THAP1 dystonia mutation causes hypomyelination and loss of YY1 binding. Human molecular genetics 12 34686877
2016 Genetic screening of THAP1 in primary dystonia patients of India. Neuroscience letters 12 27913194
2021 Reduced Expression of GABA Receptor Alpha2 Subunit Is Associated With Disinhibition of DYT-THAP1 Dystonia Patient-Derived Striatal Medium Spiny Neurons. Frontiers in cell and developmental biology 11 34095114
2019 Intracranial calcifications and dystonia associated with a novel deletion of chromosome 8p11.2 encompassing SLC20A2 and THAP1. BMJ case reports 11 31133547
2022 DYT6 mutated THAP1 is a cell type dependent regulator of the SP1 family. Brain : a journal of neurology 10 35015830
2017 In-depth Characterization of the Homodimerization Domain of the Transcription Factor THAP1 and Dystonia-Causing Mutations Therein. Journal of molecular neuroscience : MN 10 28299530
2014 Novel THAP1 variants in Brazilian patients with idiopathic isolated dystonia. Journal of the neurological sciences 10 24976531
2014 Dystonia type 6 gene product Thap1: identification of a 50 kDa DNA-binding species in neuronal nuclear fractions. Acta neuropathologica communications 10 25231164
2011 Novel THAP1 gene mutations in patients with primary dystonia from southwest China. Journal of the neurological sciences 10 21839475
2014 High variability of clinical symptoms in a Polish family with a novel THAP1 mutation. The International journal of neuroscience 8 25385508
2025 The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation. Nature communications 7 39952963
2014 DYT6 in Brazil: Genetic Assessment and Clinical Characteristics of Patients. Tremor and other hyperkinetic movements (New York, N.Y.) 7 24757586
2025 Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression. Nature communications 6 39929834
2012 Spatial Discrimination Threshold Abnormalities are not Detected in a Pilot Study of DYT6 Dystonia Mutation Carriers. Tremor and other hyperkinetic movements (New York, N.Y.) 6 23439738
2018 Generation and characterization of eight human-derived iPSC lines from affected and unaffected THAP1 mutation carriers. Stem cell research 4 30316041
2022 A case of novel DYT6 dystonia variant with serious complications after deep brain stimulation therapy: a case report. BMC neurology 3 36096774
2020 Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review. European journal of neurology 3 33175450
2019 Cerebellar Involvement in DYT-THAP1 Dystonia. Cerebellum (London, England) 3 31367947
2024 MS4A3 Promotes the Chemosensitivity of Lung Cancer via THAP1/EGFR Pathways. Critical reviews in eukaryotic gene expression 2 39180203
2024 Peripheral nerve injury induces dystonia-like movements and dysregulation in the energy metabolism: A multi-omics descriptive study in Thap1+/- mice. Neurobiology of disease 2 39732371
2022 Emerging role of a systems biology approach to elucidate factors of reduced penetrance: transcriptional changes in THAP1-linked dystonia as an example. Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V 2 38835919
2021 Pharmacological perturbation reveals deficits in D2 receptor responses in Thap1 null mice. Annals of clinical and translational neurology 2 34802187
2016 Lack of association between TOR1A and THAP1 mutations and sporadic adult-onset primary focal dystonia in a Chinese population. Clinical neurology and neurosurgery 2 26803725
2016 New THAP1 mutation and role of putative modifier in TOR1A. Acta neurologica Scandinavica 2 26940431
2015 Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions. PloS one 2 26087139
2024 Case report: Lingual dystonia symptoms treated with botulinum toxin in patients with THAP1 mutation. Dystonia (Lausanne, Switzerland) 1 40735195
2023 Transcriptional regulatory network for neuron-glia interactions and its implication for DYT6 dystonia. Dystonia (Lausanne, Switzerland) 1 38737544
2022 Changes in pallidal neural activity following long-term symptom improvement from botulinum toxin treatment in DYT6 dystonia: a case report. Journal of medical case reports 1 34998426
2014 Intrafamilial variability of the primary dystonia DYT6 phenotype caused by p.Cys5Trp mutation in THAP1 gene. Neurologia i neurochirurgia polska 1 25168324
2026 THAP1 is a maternal effect factor required for the first cell cycle via Rrm1 in early mouse embryos. EMBO reports 0 41731150
2023 Generalized Dystonia Due to a Pathogenic THAP1 Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation. Tremor and other hyperkinetic movements (New York, N.Y.) 0 37637848