TOR1A

Chr 9

torsin family 1 member A

Also known as: AMC5, DQ2, DYT1

The protein is an AAA family ATPase located in the endoplasmic reticulum lumen and expressed prominently in the substantia nigra pars compacta. Mutations cause torsion dystonia 1 (DYT1), which follows autosomal dominant inheritance with reduced penetrance, as well as autosomal recessive arthrogryposis multiplex congenita 5. The pathogenic mechanism involves dominant-negative effects that disrupt normal protein function.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 1.06
Clinical SummaryTOR1A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 155 VUS of 313 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — TOR1A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.001
Z-score 1.43
OE 0.56 (0.321.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.54Z-score
OE missense 0.89 (0.781.01)
160 obs / 180.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.321.06)
00.351.4
Missense OE0.89 (0.781.01)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 7 / 12.4Missense obs/exp: 160 / 180.2Syn Z: -0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTOR1A-related arthrogryposis multiplex congenitaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.82top 10%
GOF
0.6150th %ile
LOF
0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNEffect of torsinA on membrane proteins reveals a loss of function and a dominant-negative phenotype of the dystonia-associated DeltaE-torsinA mutantPMID:15505207

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

313 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic13
VUS155
Likely Benign67
Benign27
Conflicting9
36
Pathogenic
13
Likely Pathogenic
155
VUS
67
Likely Benign
27
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
31
0
36
Likely Pathogenic
10
1
2
0
13
VUS
9
107
37
2
155
Likely Benign
0
6
23
38
67
Benign
0
1
24
2
27
Conflicting
9
Total2211711742307

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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
Top 5 results · since 2015Search PubMed ↗