TOR2A

Chr 9

torsin family 2 member A

Also known as: TORP1

NCBI Gene: 27433ENSG00000160404UniProt: Q5JU69

This gene encodes a member of the AAA family of adenosine triphosphatases with similarity to Clp proteases and heat shock proteins. Alternative splicing at this locus results in the translation of multiple isoforms of the encoded protein, some of which contain salusin peptides in the C-terminal region. These peptides may play roles in hypotension, myocardial growth and the induction of mitogenesis, and may also be involved in the pathogenesis of atherosclerosis. The antimicrobial peptide salusin-beta has antibacterial activity. [provided by RefSeq, Nov 2014]

128
ClinVar variants
42
Pathogenic / LP
0.14
pLI score
0
Active trials
Clinical Summary— TOR2A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 63 VUS of 128 total submissions

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.
0.78LOEUF
pLI 0.136
Z-score 2.03
OE 0.30 (0.14–0.78)
Tolerant

Typical tolerance to LoF variation

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.
0.25Z-score
OE missense 0.95 (0.84–1.07)
181 obs / 190.6 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.0.30 (0.14–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.84–1.07)
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.0.98
0≤1.21.6
LoF obs/exp: 3 / 9.9Missense obs/exp: 181 / 190.6Syn Z: 0.17

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic1
VUS63
Likely Benign12
Benign1
41
Pathogenic
1
Likely Pathogenic
63
VUS
12
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
41
0
41
Likely Pathogenic
0
0
1
0
1
VUS
0
61
2
0
63
Likely Benign
0
9
0
3
12
Benign
0
1
0
0
1
Total071443118

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

View in ClinVar →

Protein Context — Lollipop Plot

TOR2A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TORSIN 2A; TOR2A
MIM #608052 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TOR2A Variants in Blepharospasm.
Saeirad S et al.·Tremor Other Hyperkinet Mov (N Y)
2023
Blepharospasm: A genetic screening study in 132 patients.
Hammer M et al.·Parkinsonism Relat Disord
2019Cohort
Genetic screening in patients of Meige syndrome and blepharospasm.
Teng X et al.·Neurol Sci
2022Cohort
Dissecting Torsin/cofactor function at the nuclear envelope: a genetic study.
Laudermilch E et al.·Mol Biol Cell
2016
Bayesian hierarchical lasso Cox model: A 9-gene prognostic signature for overall survival in gastric cancer in an Asian population.
Chu J et al.·PLoS One
2022Functional
Systematic Review of Genetic Modifiers Associated with the Development and/or Progression of Nephropathy in Patients with Sickle Cell Disease.
Labarque V et al.·Int J Mol Sci
2024Review
Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy.
Litviakov N et al.·Cancer Chemother Pharmacol
2018
Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia.
Schaefer BA et al.·PLoS One
2016
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools