TOR1AIP1

Chr 1AR

torsin 1A interacting protein 1

Also known as: LAP1, LAP1B, LAP1C, LGMD2Y

NCBI Gene: 26092 ENSG00000143337 UniProt: Q5JTV8 OMIM: 614512

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a type 2 integral membrane protein that binds A- and B-type lamins. The encoded protein localizes to the inner nuclear membrane and may be involved in maintaining the attachment of the nuclear membrane to the nuclear lamina during cell division. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.911 OMIM phenotype

Clinical Summary— TOR1AIP1

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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

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

31 unique Pathogenic / Likely Pathogenic· 270 VUS of 547 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TOR1AIP1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 1.96

OE 0.62 (0.43–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.88Z-score

OE missense 1.14 (1.05–1.25)

349 obs / 305.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.62 (0.43–0.91)

0≤0.351.4

Missense OE?1.14 (1.05–1.25)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 19 / 30.7Missense obs/exp: 349 / 305.6Syn Z: -1.28

ClinVar Variant Classifications

547 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic16

VUS270

Likely Benign194

Benign33

Conflicting11

Pathogenic

Likely Pathogenic

270

VUS

194

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	0	1	0	15
Likely Pathogenic	15	1	0	0	16
VUS	8	254	8	0	270
Likely Benign	1	3	64	126	194
Benign	0	4	25	4	33
Conflicting	—				11
Total	38	262	98	130	539

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap TOR1AIP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →