TOR1A

Chr 9ARAD

torsin family 1 member A

Also known as: AMC5, DQ2, DYT1

NCBI Gene: 1861ENSG00000136827UniProt: O14656

The protein encoded by this gene is a member of the AAA family of adenosine triphosphatases (ATPases), is related to the Clp protease/heat shock family and is expressed prominently in the substantia nigra pars compacta. Mutations in this gene result in the autosomal dominant disorder, torsion dystonia 1. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Dystonia-1, modifier of}
Arthrogryposis multiplex congenita 5MIM #618947
AR
Dystonia-1, torsionMIM #128100
AD
UniProtDystonia 1, torsion, autosomal dominant
309
ClinVar variants
46
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— TOR1A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 155 VUS of 309 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.06LOEUF
pLI 0.001
Z-score 1.43
OE 0.56 (0.32–1.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.54Z-score
OE missense 0.89 (0.78–1.01)
160 obs / 180.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.32–1.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.78–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 7 / 12.4Missense obs/exp: 160 / 180.2Syn Z: -0.09

ClinVar Variant Classifications

309 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic11
VUS155
Likely Benign66
Benign27
Conflicting9
35
Pathogenic
11
Likely Pathogenic
155
VUS
66
Likely Benign
27
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
33
0
35
Likely Pathogenic
4
0
7
0
11
VUS
7
104
42
2
155
Likely Benign
0
5
23
38
66
Benign
0
1
24
2
27
Conflicting
—9
Total1111212942303

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TOR1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TOR1A-related arthrogryposis multiplex congenita

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
frameshift variantstop gainedmissense variantinframe deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TORSIN 1A; TOR1A
MIM #605204 · *

{Dystonia-1, modifier of}

Molecular basis of disorder known

Arthrogryposis multiplex congenita 5

MIM #618947

Molecular basis of disorder known

Autosomal recessive

Dystonia-1, torsion

MIM #128100

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dystonia.
Balint B et al.·Nat Rev Dis Primers
2018Review
Genetics and Pathogenesis of Dystonia.
Thomsen M et al.·Annu Rev Pathol
2024Review
Genetic Update and Treatment for Dystonia.
Koptielow J et al.·Int J Mol Sci
2024Review
The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.
Saffari A et al.·Brain
2023
Expanding the genotypes and phenotypes for 19 rare diseases by exome sequencing performed in pediatric intensive care unit.
Liu J et al.·Hum Mutat
2021
Dystonia.
Morgante F et al.·Continuum (Minneap Minn)
2013Review
Genetics in dystonia.
Klein C·Parkinsonism Relat Disord
2014Review
Pathophysiology of Dyt1-Tor1a dystonia in mice is mediated by spinal neural circuit dysfunction.
Pocratsky AM et al.·Sci Transl Med
2023
The Role of TOR1A Polymorphisms in Dystonia: A Systematic Review and Meta-Analysis.
Siokas V et al.·PLoS One
2017Meta-analysis
Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review.
Gómez-Garre P et al.·Eur J Neurol
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
DystoniaMovement DisordersCombined Dystonia

Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia

NOT YET RECRUITING
NCT06999096Phase NAUniversity Hospital, Strasbourg, FranceStarted 2025-08
Long-read whole genome sequencing

External Resources

Links to major genomics databases and tools