TOR1AIP1

Chr 1AR

torsin 1A interacting protein 1

Also known as: LAP1, LAP1B, LAP1C, LGMD2Y

This gene encodes a protein that maintains nuclear membrane integrity by binding A- and B-type lamins and facilitating the proper localization and ATPase activity of TOR1A and TOR1B proteins at the nuclear membrane. Mutations cause autosomal recessive muscular dystrophy characterized by rigid spine and distal joint contractures. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.911 OMIM phenotype
Clinical SummaryTOR1AIP1
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Gene-Disease Validity (ClinGen)
TOR1AIP1-related multisystem disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 241 VUS of 500 total submissions
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GeneReview available — TOR1AIP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.91LOEUF
pLI 0.000
Z-score 1.96
OE 0.62 (0.430.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.88Z-score
OE missense 1.14 (1.051.25)
349 obs / 305.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.62 (0.430.91)
00.351.4
Missense OE1.14 (1.051.25)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 19 / 30.7Missense obs/exp: 349 / 305.6Syn Z: -1.28

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic13
VUS241
Likely Benign183
Benign25
Conflicting6
24
Pathogenic
13
Likely Pathogenic
241
VUS
183
Likely Benign
25
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
12
0
24
Likely Pathogenic
13
0
0
0
13
VUS
7
226
8
0
241
Likely Benign
0
1
59
123
183
Benign
0
0
24
1
25
Conflicting
6
Total32227103124492

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗