TOR1AIP1

torsin 1A interacting protein 1

Basic information

Region (hg38): 1:179882042-179920077

Links

ENSG00000143337 ∙ NCBI:26092 ∙ OMIM:614512 ∙ HGNC:29456 ∙ Uniprot:Q5JTV8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2Y (Moderate), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2Y (Supportive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2Y (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures	AR	Cardiovascular; Pulmonary	Individuals have been described with cardiomyopathy and pulmonary restrictive disease, and awareness may allow medical management	Cardiovascular; Musculoskeletal; Neurologic; Pulmonary	24856141

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TOR1AIP1 gene.

• Autosomal recessive limb-girdle muscular dystrophy type 2Y (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOR1AIP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				95	2	97
missense		1	200	3	4	208
nonsense	6	2	1			9
start loss			1			1
frameshift	4	1	4			9
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)		7	1	1	1	10
splice region			7	9	2	18
non coding			9	45	19	73
Total	10	11	218	145	26

Highest pathogenic variant AF is 0.0000131

Variants in TOR1AIP1

This is a list of pathogenic ClinVar variants found in the TOR1AIP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-179882051-C-G			Benign (Jul 26, 2018)
1-179882173-C-T			Benign (Jul 26, 2018)
1-179882506-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Jul 29, 2022)
1-179882506-GCGGGCGA-G		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Pathogenic (Feb 22, 2020)
1-179882509-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Apr 11, 2023)
1-179882513-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Apr 11, 2019)
1-179882515-G-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
1-179882517-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Likely benign (Jun 27, 2022)
1-179882518-C-G		Inborn genetic diseases	Uncertain significance (Mar 24, 2023)
1-179882522-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Apr 25, 2019)
1-179882526-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Likely benign (Mar 07, 2020)
1-179882527-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Mar 18, 2022)
1-179882529-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Likely benign (Feb 15, 2020)
1-179882531-C-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Oct 03, 2023)
1-179882532-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Likely benign (May 08, 2023)
1-179882537-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Aug 28, 2022)
1-179882539-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y • Inborn genetic diseases	Uncertain significance (Oct 01, 2024)
1-179882540-A-T		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Jan 26, 2021)
1-179882545-T-C		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Jun 26, 2022)
1-179882546-G-C		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
1-179882549-G-T		Autosomal recessive limb-girdle muscular dystrophy type 2Y • Inborn genetic diseases	Uncertain significance (Jun 05, 2022)
1-179882557-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Feb 03, 2022)
1-179882558-T-A		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Nov 01, 2021)
1-179882560-A-AC		Centronuclear myopathy	Pathogenic (Mar 01, 2024)
1-179882564-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2Y	Uncertain significance (Dec 03, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOR1AIP1	protein_coding	protein_coding	ENST00000606911	10	42959

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.27e-9	0.937	124302	39	1407	125748	0.00577

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.883	349	306	1.14	0.0000152	3758
Missense in Polyphen		123	130.58	0.94197		1596
Synonymous	-1.28	136	118	1.15	0.00000548	1168
Loss of Function	1.96	19	30.7	0.618	0.00000166	332

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00352	0.00352
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0675	0.0674
Finnish	0.00271	0.00268
European (Non-Finnish)	0.000231	0.000229
Middle Eastern	0.0675	0.0674
South Asian	0.00130	0.00127
Other	0.00132	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000269|PubMed:23569223}.

Recessive Scores

• pRec: 0.0757

Intolerance Scores

• loftool: 0.800
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.66

Haploinsufficiency Scores

• pHI: 0.0821
• hipred: N
• hipred_score: 0.233
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.941

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tor1aip1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype

Gene ontology

• Biological process: positive regulation of ATPase activity;protein localization to nucleus;nuclear membrane organization
• Cellular component: nucleus;nuclear inner membrane;integral component of membrane;nuclear membrane
• Molecular function: ATPase activator activity;protein binding;lamin binding;cytoskeletal protein binding;ATPase binding