TOR1AIP1

Chr 1AR

torsin 1A interacting protein 1

NCBI Gene: 26092ENSG00000143337UniProt: Q5JTV8

Required for nuclear membrane integrity. Induces TOR1A and TOR1B ATPase activity and is required for their location on the nuclear membrane. Binds to A- and B-type lamins. Possible role in membrane attachment and assembly of the nuclear lamina

Primary Disease Associations & Inheritance

?Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contracturesMIM #617072
AR
UniProtMyopathy, autosomal recessive, with rigid spine and distal joint contractures
576
ClinVar variants
49
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TOR1AIP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 Pathogenic / Likely Pathogenic· 204 VUS of 576 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.
0.91LOEUF
pLI 0.000
Z-score 1.96
OE 0.62 (0.43–0.91)
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.
-0.88Z-score
OE missense 1.14 (1.05–1.25)
349 obs / 305.6 exp
Tolerant

Tolerant to missense variation

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.0.62 (0.43–0.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.14 (1.05–1.25)
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.1.15
0≤1.21.6
LoF obs/exp: 19 / 30.7Missense obs/exp: 349 / 305.6Syn Z: -1.28

ClinVar Variant Classifications

576 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic12
VUS204
Likely Benign175
Benign32
Conflicting8
37
Pathogenic
12
Likely Pathogenic
204
VUS
175
Likely Benign
32
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
32
0
37
Likely Pathogenic
9
1
2
0
12
VUS
6
190
8
0
204
Likely Benign
1
2
64
108
175
Benign
0
4
25
3
32
Conflicting
—8
Total21197131111468

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

View in ClinVar →

Protein Context — Lollipop Plot

TOR1AIP1 · 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

?Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures

MIM #617072

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
TOR1AIP1-Associated Nuclear Envelopathies.
Mackels L et al.·Int J Mol Sci
2023Review
[Congenital Myasthenic Syndromes].
Ohno K·Brain Nerve
2024
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force.
Wang QS et al.·Nat Commun
2022
A TOR1AIP1 variant segregating with an early onset limb girdle myasthenia-Support for the role of LAP1 in NMJ function and disease.
Malfatti E et al.·Neuropathol Appl Neurobiol
2022Case report
Selective loss of a LAP1 isoform causes a muscle-specific nuclear envelopathy.
Lornage X et al.·Neurogenetics
2021Case report
TOR1 AIP1 interacts with p53 to enhance cell cycle dysregulation in prostate cancer progression.
Li Z et al.·Mol Cell Biochem
2025
TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle muscular dystrophy.
Ghaoui R et al.·Neuromuscul Disord
2016Case report
Magnetic Resonance Imaging characteristics in case of TOR1AIP1 muscular dystrophy.
Bhatia A et al.·Clin Imaging
2019Case report
Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies.
Lessel I et al.·Hum Genet
2020Case report
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