Dystonia 3, Torsion, X-Linked (TAF1)
| Dred_ID | RD00050 |
| OMIM ID | 314250 |
| Disease name | Dystonia 3, Torsion, X-Linked |
| Alternative names | DYT3 |
| Category | Genetic diseases Rare diseases |
| Phenotype | MalaCards based summary : Dystonia 3, Torsion, X-Linked, also known as x-linked dystonia-parkinsonism, is related to dystonia 1, torsion, autosomal dominant and parkinsonism, and has symptoms including tremor, myoclonus and dystonia. An important gene associated with Dystonia 3, Torsion, X-Linked is TAF1 (TATA-Box Binding Protein Associated Factor 1), and among its related pathways/superpathways is Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases. The drugs Mung bean and Botulinum Toxins have been mentioned in the context of this disorder. Affiliated tissues include caudate nucleus, tongue and brain, and related phenotypes are chorea and myoclonus. |
| Miscellaneouse | onset in fourth decade described predominantly in families from the philippines symptoms begin focally, later segmental or generalized women may be mildly affected associated with a disease-specific sequence change, referred to as 'dsc3,' within an open-reading frame (orf) of a 'multiple transcript system' known as dyt3 |
| Prevalence | Prevalence: <1/1000000 (Europe),1-9/1000000 (Philippines); [source: MalaCards] |
| Inheritance | X-linked recessive |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | TAF1 |
| Alias symbols | OF; XDP; BA2R; CCG1; CCGS; DYT3; KAT4; P250; NSCL2; TAF2A; MRXS33; N-TAF1; TAFII250; DYT3/TAF1; TAFII-250; TAF(II)250 |
| Gene name | TATA-box binding protein associated factor 1 |
| Gene map locus | Xq13.1; chrX:71,366,264-71,466,005(+) |
| Ensembl Gene ID | ENSG00000147133 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor TFIID, which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N- and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme. Mutations in this gene result in Dystonia 3, torsion, X-linked, a dystonia-parkinsonism disorder. Alternative splicing of this gene results in multiple transcript variants. This gene is part of a complex transcription unit (TAF1/DYT3), wherein some transcript variants share exons with TAF1 as well as additional downstream DYT3 exons. |
| Repeat unit | CCCTCT |
| Normal repeat copies | <35 |
| Pathogenic repeat copies | ≥35 |
| Gene | TAF1 |
| Repeat location | intron |
| Chromosome locus | chrX:71432900-71432906 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | XDP is associated with a SINE-VNTR-Alu (SVA)-type retrotransposon insertion within the TAF1 gene. This element includes a hexameric DNA repeat expansion, (CCCTCT)n, the length of which varies among patients and is inversely correlated to age of disease onset. In cell models, the SVA alters TAF1 splicing and reduces levels of full-length transcript. Neuroimaging data have confirmed previous neuropathology studies that XDP involves a progressive striatal atrophy, while further detecting functional alterations in additional brain regions. In patients exhibiting features of both dystonia and parkinsonism, pallidal DBS has resulted in rapid improvement of hyperkinetic movements, but effects on hypokinetic features have been inconsistent. |
| Pathway annotation | Reactome, KEGG |