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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TOR1A
torsin family 1 member A
Chromosome 9 Β· 9q34.11
NCBI Gene: 1861Ensembl: ENSG00000136827.12HGNC: HGNC:3098UniProt: B3KPA1
238PubMed Papers
22Diseases
0Drugs
15Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein deneddylationprotein bindingidentical protein bindingATP-dependent protein folding chaperonearthrogryposis multiplex congenita 5early-onset generalized limb-onset dystoniadystonic disorderPrimary dystonia, DYT4 type
✦AI Summary

TOR1A encodes torsin-1A, an AAA+ ATPase chaperone protein that plays crucial roles in protein quality control and cellular organization. The protein functions primarily in the endoplasmic reticulum and nuclear envelope, where it assists in protein folding, prevents misfolded protein aggregation, and maintains nuclear envelope integrity 1. TOR1A is particularly important in neuronal function, regulating synaptic vesicle recycling and dopamine neurotransmission through control of dopamine transporter localization 1. The gene exhibits complex inheritance patterns with distinct disease associations. Heterozygous mutations cause DYT1 dystonia, an early-onset generalized dystonia with reduced penetrance and autosomal dominant inheritance 2. Meta-analysis has identified specific TOR1A polymorphisms (rs1182 and rs1801968) associated with focal dystonia and writer's cramp 3. In contrast, biallelic TOR1A variants cause arthrogryposis multiplex congenita 5 (AMC5), a severe neurodevelopmental disorder characterized by congenital contractures, developmental delay, and high mortality 4. The protein's dysfunction contributes to endoplasmic reticulum stress response pathways implicated in dystonia pathogenesis 1, highlighting its critical role in maintaining neuronal proteostasis and proper brain network function.

Sources cited
1
TOR1A functions in endoplasmic reticulum stress response and protein quality control pathways in dystonia pathogenesis
PMID: 37738511
2
Heterozygous TOR1A mutations cause DYT1 dystonia with autosomal dominant inheritance
PMID: 38612382
3
Meta-analysis identified TOR1A polymorphisms rs1182 and rs1801968 associated with focal dystonia and writer's cramp
PMID: 28081261
4
Biallelic TOR1A variants cause arthrogryposis multiplex congenita 5 (AMC5), a severe neurodevelopmental disorder with high mortality
PMID: 36757831
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜22
arthrogryposis multiplex congenita 5Open Targets
0.78Strong
early-onset generalized limb-onset dystoniaOpen Targets
0.73Strong
dystonic disorderOpen Targets
0.65Moderate
Primary dystonia, DYT4 typeOpen Targets
0.60Moderate
DystoniaOpen Targets
0.53Moderate
genetic disorderOpen Targets
0.45Moderate
prostate carcinomaOpen Targets
0.42Moderate
arthrogryposis multiplex congenitaOpen Targets
0.37Weak
nervous system diseaseOpen Targets
0.30Weak
complicationOpen Targets
0.30Weak
Herpes ZosterOpen Targets
0.30Weak
smoking initiationOpen Targets
0.29Weak
hereditary ataxiaOpen Targets
0.12Weak
Flexion contractureOpen Targets
0.11Weak
Romano-Ward syndromeOpen Targets
0.08Suggestive
familial atrial fibrillationOpen Targets
0.08Suggestive
atrial fibrillationOpen Targets
0.07Suggestive
Familial short QT syndromeOpen Targets
0.07Suggestive
Brugada syndromeOpen Targets
0.07Suggestive
Familial progressive cardiac conduction defectOpen Targets
0.07Suggestive
Arthrogryposis multiplex congenita 5UniProt
Dystonia 1, torsion, autosomal dominantUniProt
Pathogenic Variants15
NM_000113.3(TOR1A):c.862C>T (p.Arg288Ter)Pathogenic
Early-onset generalized limb-onset dystonia|Arthrogryposis multiplex congenita 5|not provided|Dystonic disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 288
NM_000113.3(TOR1A):c.904GAG[1] (p.Glu303del)Pathogenic
Early-onset generalized limb-onset dystonia|not provided|Dystonic disorder|Inborn genetic diseases|TOR1A-related disorder|Early-onset generalized limb-onset dystonia;Arthrogryposis multiplex congenita 5|Arthrogryposis multiplex congenita 5
β˜…β˜…β˜†β˜†2026β†’ Residue 303
NM_000113.3(TOR1A):c.844C>T (p.Arg282Ter)Likely pathogenic
Arthrogryposis multiplex congenita 5
β˜…β˜…β˜†β˜†2023β†’ Residue 282
NM_000113.3(TOR1A):c.349_352delinsTAGT (p.Glu117_Asn118delinsTer)Pathogenic
Arthrogryposis multiplex congenita 5
β˜…β˜†β˜†β˜†2025β†’ Residue 117
NM_000113.3(TOR1A):c.621-2A>GLikely pathogenic
Arthrogryposis multiplex congenita 5
β˜…β˜†β˜†β˜†2025
NM_000113.3(TOR1A):c.856C>T (p.Gln286Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 286
NM_000113.3(TOR1A):c.748+1G>ALikely pathogenic
TOR1A-related disorder
β˜…β˜†β˜†β˜†2023
NM_000113.3(TOR1A):c.287_288del (p.Leu96fs)Likely pathogenic
Arthrogryposis multiplex congenita 5
β˜…β˜†β˜†β˜†2023β†’ Residue 96
NM_000113.3(TOR1A):c.461G>A (p.Trp154Ter)Pathogenic
Early-onset generalized limb-onset dystonia
β˜…β˜†β˜†β˜†2022β†’ Residue 154
NM_000113.3(TOR1A):c.958A>G (p.Lys320Glu)Pathogenic
Early-onset generalized limb-onset dystonia
β˜…β˜†β˜†β˜†2022β†’ Residue 320
NM_000113.3(TOR1A):c.214C>T (p.Gln72Ter)Pathogenic
Early-onset generalized limb-onset dystonia
β˜…β˜†β˜†β˜†2021β†’ Residue 72
NM_000113.3(TOR1A):c.961del (p.Thr321fs)Likely pathogenic
Arthrogryposis multiplex congenita 5|Inborn genetic diseases
β˜…β˜†β˜†β˜†2019β†’ Residue 321
NM_000113.3(TOR1A):c.790_793del (p.Asp264fs)Likely pathogenic
Arthrogryposis multiplex congenita 5
β˜…β˜†β˜†β˜†β†’ Residue 264
NM_000113.3(TOR1A):c.486T>A (p.Cys162Ter)Likely pathogenic
Arthrogryposis multiplex congenita 5
β˜…β˜†β˜†β˜†β†’ Residue 162
NM_000113.3(TOR1A):c.952G>A (p.Gly318Ser)Pathogenic
Arthrogryposis multiplex congenita 5
β˜†β˜†β˜†β˜†2020β†’ Residue 318
View on ClinVar β†—
Related Genes
TNFRSF25Protein interaction100%HLA-DQA1Protein interaction95%TGM2Protein interaction93%TOR1AIP2Protein interaction91%HLA-DMAProtein interaction90%TUBB4AProtein interaction90%
Tissue Expression6 tissues
Brain
100%
Liver
88%
Bone Marrow
85%
Lung
72%
Heart
58%
Ovary
50%
Gene Interaction Network
Click a node to explore
TOR1ATNFRSF25HLA-DQA1TGM2TOR1AIP2HLA-DMATUBB4A
PROTEIN STRUCTURE
Preparing viewer…
PDB5J1S Β· 1.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.84LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.57 [0.39–0.84]
RankingsWhere TOR1A stands among ~20K protein-coding genes
  • #1,657of 20,598
    Most Researched238 Β· top 10%
  • #2,437of 5,498
    Most Pathogenic Variants15
  • #7,222of 17,882
    Most Constrained (LOEUF)0.84
Genes detectedTOR1A
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Genetics and Pathogenesis of Dystonia.
PMID: 37738511
Annu Rev Pathol Β· 2024
1.00
2
Genetic Update and Treatment for Dystonia.
PMID: 38612382
Int J Mol Sci Β· 2024
0.90
3
Myoclonus-dystonia syndrome.
PMID: 21496608
Handb Clin Neurol Β· 2011
0.80
4
Dystonia-plus syndromes.
PMID: 20590807
Eur J Neurol Β· 2010
0.70
5
Addressing variant pathogenicity: the TorsinA (TOR1A) gene as a model.
PMID: 25125254
Hum Mutat Β· 2014
0.68