The TOR1A gene (also known as DYT1) provides instructions for making a protein called torsinA. This protein is found in the space between two neighboring structures within cells, the nuclear envelope and the endoplasmic reticulum. The nuclear envelope surrounds the nucleus and separates it from the rest of the cell. The endoplasmic reticulum processes proteins and other molecules and helps transport them to specific destinations either inside or outside the cell. Although little is known about the function of torsinA, studies suggest that it may help process and transport other proteins. TorsinA may also participate in the movement of membranes associated with the nuclear envelope and endoplasmic reticulum, and in stress response signaling.
TorsinA is active in many of the body's tissues, and it is particularly important for the normal function of nerve cells in the brain. For example, researchers have found high levels of torsinA in a part of the brain called the substantia nigra. This region contains nerve cells that produce dopamine, a chemical messenger that transmits signals within the brain to produce smooth physical movements.
Health Conditions Related to Genetic Changes
Early-onset isolated dystonia
A particular variant (also called a mutation) in the TOR1A gene causes most cases of early-onset isolated dystonia. This condition is one of many forms of dystonia, which is a group of conditions characterized by involuntary tensing of the muscles (muscle contractions), twisting of specific body parts such as an arm or a leg, rhythmic shaking (tremors), and other uncontrolled movements.
This TOR1A gene variant, which is often called the GAG deletion or delta GAG, deletes three DNA building blocks (base pairs) from the TOR1A gene. The resulting torsinA protein is missing one protein building block (amino acid) in a critical region. The altered protein's effect on the function of nerve cells in the brain is unclear. People with early-onset isolated dystonia do not have a loss of nerve cells or obvious changes in the structure of the brain that would explain the abnormal muscle contractions seen with this condition. Instead, the altered torsinA protein may have subtle effects on the connections between nerve cells and likely disrupts chemical signaling between nerve cells that control movement and sensory feedback in the brain. Researchers are working to determine how a change in this protein leads to the characteristic features of early-onset isolated dystonia.More About This Health Condition
Benign essential blepharospasm
Several studies have examined a possible relationship between common variations (polymorphisms) in the TOR1A gene and several forms of adult-onset dystonia, most commonly dystonia isolated to a certain body region (task-specific focal dystonia), abnormal posture and spasms of the hand while attempting to write (writer's cramp), and spasms of the eyelids in the form of benign essential blepharospasm. The results of these studies have been mixed. Some research has suggested that certain polymorphisms increase a person's risk of developing these forms of dystonia. However, other studies have found no connection between changes in the TOR1A gene and condition risk. Researchers are still working to clarify whether variants of the TOR1A gene are related to adult-onset dystonias.More About This Health Condition
Other Names for This Gene
- Dystonia 1 protein
- dystonia 1, torsion (autosomal dominant; torsinA)
- torsin family 1, member A (torsin A)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Asanuma K, Ma Y, Okulski J, Dhawan V, Chaly T, Carbon M, Bressman SB, Eidelberg D. Decreased striatal D2 receptor binding in non-manifesting carriers of the DYT1 dystonia mutation. Neurology. 2005 Jan 25;64(2):347-9. doi: 10.1212/01.WNL.0000149764.34953.BF. Citation on PubMed
- Breakefield XO, Blood AJ, Li Y, Hallett M, Hanson PI, Standaert DG. The pathophysiological basis of dystonias. Nat Rev Neurosci. 2008 Mar;9(3):222-34. doi: 10.1038/nrn2337. Citation on PubMed
- Domingo A, Yadav R, Ozelius LJ. Isolated dystonia: clinical and genetic updates. J Neural Transm (Vienna). 2021 Apr;128(4):405-416. doi: 10.1007/s00702-020-02268-x. Epub 2020 Nov 27. Citation on PubMed
- Gomez-Garre P, Jesus S, Perinan MT, Adarmes A, Alonso-Canovas A, Blanco-Ollero A, Buiza-Rueda D, Carrillo F, Catalan-Alonso MJ, Del Val J, Escamilla-Sevilla F, Espinosa-Rosso R, Fernandez-Moreno MC, Garcia-Moreno JM, Garcia-Ruiz PJ, Giacometti-Silveira S, Gutierrez-Garcia J, Lopez-Valdes E, Macias-Garcia D, Martinez-Castrillo JC, Martinez-Torres I, Medialdea-Natera MP, Minguez-Castellanos A, Moya MA, Ochoa-Sepulveda JJ, Ojea T, Rodriguez N, Sillero-Sanchez M, Tejera-Parrado C, Mir P. Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review. Eur J Neurol. 2021 Apr;28(4):1188-1197. doi: 10.1111/ene.14638. Epub 2020 Dec 6. Citation on PubMed
- Goodchild RE, Dauer WT. Mislocalization to the nuclear envelope: an effect of the dystonia-causing torsinA mutation. Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):847-52. doi: 10.1073/pnas.0304375101. Epub 2004 Jan 7. Citation on PubMed
- Goodchild RE, Dauer WT. The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. J Cell Biol. 2005 Mar 14;168(6):855-62. doi: 10.1083/jcb.200411026. Citation on PubMed
- Hewett JW, Tannous B, Niland BP, Nery FC, Zeng J, Li Y, Breakefield XO. Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells. Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7271-6. doi: 10.1073/pnas.0701185104. Epub 2007 Apr 11. Citation on PubMed or Free article on PubMed Central
- Kabakci K, Hedrich K, Leung JC, Mitterer M, Vieregge P, Lencer R, Hagenah J, Garrels J, Witt K, Klostermann F, Svetel M, Friedman J, Kostic V, Bressman SB, Breakefield XO, Ozelius LJ, Pramstaller PP, Klein C. Mutations in DYT1: extension of the phenotypic and mutational spectrum. Neurology. 2004 Feb 10;62(3):395-400. doi: 10.1212/01.wnl.0000113024.84178.f7. Citation on PubMed
- Klein C, Lohmann K, Marras C, Munchau A. Hereditary Dystonia Overview. 2003 Oct 28 [updated 2017 Jun 22]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1155/ Citation on PubMed
- Nery FC, Armata IA, Farley JE, Cho JA, Yaqub U, Chen P, da Hora CC, Wang Q, Tagaya M, Klein C, Tannous B, Caldwell KA, Caldwell GA, Lencer WI, Ye Y, Breakefield XO. TorsinA participates in endoplasmic reticulum-associated degradation. Nat Commun. 2011 Jul 12;2:393. doi: 10.1038/ncomms1383. Citation on PubMed
- Ozelius LJ, Hewett JW, Page CE, Bressman SB, Kramer PL, Shalish C, de Leon D, Brin MF, Raymond D, Corey DP, Fahn S, Risch NJ, Buckler AJ, Gusella JF, Breakefield XO. The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nat Genet. 1997 Sep;17(1):40-8. doi: 10.1038/ng0997-40. Citation on PubMed
- Rittiner JE, Caffall ZF, Hernandez-Martinez R, Sanderson SM, Pearson JL, Tsukayama KK, Liu AY, Xiao C, Tracy S, Shipman MK, Hickey P, Johnson J, Scott B, Stacy M, Saunders-Pullman R, Bressman S, Simonyan K, Sharma N, Ozelius LJ, Cirulli ET, Calakos N. Functional Genomic Analyses of Mendelian and Sporadic Disease Identify Impaired eIF2alpha Signaling as a Generalizable Mechanism for Dystonia. Neuron. 2016 Dec 21;92(6):1238-1251. doi: 10.1016/j.neuron.2016.11.012. Epub 2016 Dec 8. Citation on PubMed
- Rostasy K, Augood SJ, Hewett JW, Leung JC, Sasaki H, Ozelius LJ, Ramesh V, Standaert DG, Breakefield XO, Hedreen JC. TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion. Neurobiol Dis. 2003 Feb;12(1):11-24. doi: 10.1016/s0969-9961(02)00010-4. Citation on PubMed
- Sharma N, Franco RA Jr, Kuster JK, Mitchell AA, Fuchs T, Saunders-Pullman R, Raymond D, Brin MF, Blitzer A, Bressman SB, Ozelius LJ. Genetic evidence for an association of the TOR1A locus with segmental/focal dystonia. Mov Disord. 2010 Oct 15;25(13):2183-7. doi: 10.1002/mds.23225. Citation on PubMed
- Walker RH, Shashidharan P. Developments in the molecular biology of DYT1 dystonia. Mov Disord. 2003 Oct;18(10):1102-7. doi: 10.1002/mds.10549. Citation on PubMed
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