TOR1AIP1

Summary

TOR1AIP1 (torsin 1A interacting protein 1, HGNC:29456) is a protein-coding gene on chromosome 1q25.2, encoding Torsin-1A-interacting protein 1 (Q5JTV8). Required for nuclear membrane integrity.

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.

Source: NCBI Gene 26092 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TOR1AIP1-related multisystem disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 364 total — 4 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_015602

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29456
Approved symbol	TOR1AIP1
Name	torsin 1A interacting protein 1
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Aliases	LAP1B, FLJ13142, LAP1, LAP1C
Ensembl gene	ENSG00000143337
Ensembl biotype	protein_coding
OMIM	614512
Entrez	26092

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000271583, ENST00000435319, ENST00000447964, ENST00000474875, ENST00000524653, ENST00000527391, ENST00000527867, ENST00000528443, ENST00000529091, ENST00000531630, ENST00000531726, ENST00000606911

RefSeq mRNA: 2 — MANE Select: NM_015602 NM_001267578, NM_015602

CCDS: CCDS1335, CCDS65737

Canonical transcript exons

ENST00000606911 — 10 exons

Exon	Start	End
ENSE00002178422	179882285	179882977
ENSE00003483184	179901302	179901388
ENSE00003536688	179884692	179884769
ENSE00003633018	179900126	179900167
ENSE00003653233	179889313	179889369
ENSE00003698492	179917452	179920076
ENSE00003703708	179903966	179904022
ENSE00003707546	179907823	179907864
ENSE00003711472	179908605	179908673
ENSE00003787683	179913998	179914054

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 97.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.0039 / max 447.2213, expressed in 1822 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6933	27.0415	1803
6928	20.8509	1754
6932	1.0921	697
6931	0.9578	634
6925	0.7293	264
6926	0.6755	391
6927	0.4662	241
6924	0.3915	168
6930	0.3306	149
6929	0.2552	85

Top tissues by expression

300 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	97.92	gold quality
urethra	UBERON:0000057	97.65	gold quality
calcaneal tendon	UBERON:0003701	97.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.49	gold quality
blood vessel layer	UBERON:0004797	97.45	gold quality
cauda epididymis	UBERON:0004360	97.29	gold quality
caput epididymis	UBERON:0004358	97.23	gold quality
decidua	UBERON:0002450	97.05	gold quality
corpus epididymis	UBERON:0004359	97.04	gold quality
germinal epithelium of ovary	UBERON:0001304	97.03	gold quality
parietal pleura	UBERON:0002400	96.95	gold quality
seminal vesicle	UBERON:0000998	96.94	gold quality
trabecular bone tissue	UBERON:0002483	96.91	gold quality
palpebral conjunctiva	UBERON:0001812	96.87	gold quality
synovial joint	UBERON:0002217	96.86	gold quality
biceps brachii	UBERON:0001507	96.85	gold quality
sperm	CL:0000019	96.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.74	gold quality
mammary duct	UBERON:0001765	96.73	gold quality
parotid gland	UBERON:0001831	96.69	gold quality
bone marrow	UBERON:0002371	96.61	gold quality
tibia	UBERON:0000979	96.48	gold quality
epithelium of mammary gland	UBERON:0003244	96.36	gold quality
eye	UBERON:0000970	96.35	gold quality
pleura	UBERON:0000977	96.35	gold quality
gluteal muscle	UBERON:0002000	96.22	gold quality
saphenous vein	UBERON:0007318	96.03	gold quality
body of tongue	UBERON:0011876	95.91	gold quality
lower lobe of lung	UBERON:0008949	95.87	gold quality
vena cava	UBERON:0004087	95.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

79 targeting TOR1AIP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-543	99.52	69.03	2595

Literature-anchored findings (GeneRIF, showing 9)

• Molecular cloning of LAP1B & the role of the protein domains in localization of LAP1B to nuclear and endoplasmic reticulum membranes was determined (PMID:12061773)
• Data indicate that the protein phosphatase 1 (PP1) binding domain in nuclear membrane protein lamina associated polypeptide 1B (LAP1B) was here identified as the REVRF motif at amino acids 55-59. (PMID:24116158)
• study described a new autosomal recessive nuclear envelope disease caused by a homozygous mutation in exon 1 of TOR1AIP1 encoding LAP1B; study expands the spectrum of genes associated with nuclear envelopathies and highlights critical function for LAP1B in striated muscle (PMID:24856141)
• Data show that mutation of arginine 563 in lamina-associated polypeptide 1 (LAP1) reduces its ability to stimulate TorsinA ATPase hydrolysis. (PMID:25149450)
• LAP1 co-localizes with acetylated alpha-tubulin in the mitotic spindle and with gamma-tubulin in centrosomes (main microtubule organizing center) in mitotic cells. (PMID:25323962)
• LAP1 protein encoded by TOR1AIP1 may play a role in dysferlinopathy pathogenesis (PMID:28110863)
• All seven patients are homozygous for a nonsense mutation in the TOR1AIP1 gene resulting in the loss of both protein isoforms LAP1B and LAP1C. (PMID:30723199)
• Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies. (PMID:32055997)
• TOR1AIP1-Associated Nuclear Envelopathies. (PMID:37108075)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:112962	ENSDARG00000069102
danio_rerio	si:dkeyp-82a1.6	ENSDARG00000094336
mus_musculus	Tor1aip1	ENSMUSG00000026466
rattus_norvegicus	Tor1aip1	ENSRNOG00000003946

Paralogs (1): TOR1AIP2 (ENSG00000169905)

Protein

Protein identifiers

Torsin-1A-interacting protein 1 — Q5JTV8 (reviewed: Q5JTV8)

Alternative names: Lamin-associated protein 1B

All UniProt accessions (6): Q5JTV8, H0Y4R4, H0YD16, H0YDJ8, H0YDU3, J3KN66

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with ATP1B4. Interacts with TOR1A (ATP-bound). Interacts with TOR1B, TOR2A and TOR3A. Interacts with VIM.

Subcellular location. Nucleus inner membrane Nucleus envelope. Nucleus.

Tissue specificity. Expressed in muscle, liver and kidney. Major isoform present in liver, brain and heart (at protein level). Expressed at lower levels than isoform 4 in lung, kidney and spleen (at protein level). Similar levels of isoforms 1 and 4 are observed in ovary, testis and pancreas (at protein level). Expressed at higher levels than isoform 1 in lung, kidney and spleen (at protein level). Expressed at lower levels than isoform 1 in liver, brain and heart (at protein level). Similar levels of isoforms 1 and 4 are observed in ovary, testis and pancreas (at protein level).

Post-translational modifications. Phosphorylated. Dephosphorylated at Ser-309 and Ser-315 by serine/threonine-protein phosphatase PP1.

Disease relevance. Myopathy, autosomal recessive, with rigid spine and distal joint contractures (MRRSDC) [MIM:617072] An autosomal recessive degenerative myopathy characterized by muscle weakness initially involving the proximal lower limbs, followed by distal upper and lower limb muscle weakness and atrophy. Other features include joint contractures, rigid spine, and restricted pulmonary function. Cardiac involvement has been observed in some patients. Disease onset is in the first or second decades of life. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Produced by alternative promoter usage.

Similarity. Belongs to the TOR1AIP family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5JTV8-1	1, LAP1B	yes
Q5JTV8-2	2
Q5JTV8-3	3
Q5JTV8-4	4, LAP1C

RefSeq proteins (2): NP_001254507, NP_056417* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008662	TOIP1/2	Family
IPR038599	LAP1C-like_C_sf	Homologous_superfamily
IPR046753	TOIP1/2_C	Domain
IPR046754	TOIP1/2_N	Domain

Pfam: PF05609, PF20443

UniProt features (67 total): modified residue 18, helix 13, compositionally biased region 7, strand 7, sequence variant 4, region of interest 4, splice variant 3, topological domain 2, sequence conflict 2, turn 2, chain 1, transmembrane region 1, glycosylation site 1, cross-link 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4TVS	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JTV8-F1	61.93	0.33

Antibody-complex structures (SAbDab): 1 — 4TVS

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (19): 60, 135, 143, 146, 154, 156, 157, 186, 215, 220, 227, 230, 242, 301, 305, 309, 315, 552, 308

Glycosylation sites (1): 399

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9035034	RHOF GTPase cycle

MSigDB gene sets: 288 (showing top): GCANCTGNY_MYOD_Q6, CMYB_01, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, CAGCTG_AP4_Q5, BILD_HRAS_ONCOGENIC_SIGNATURE, MORF_RAF1, ONKEN_UVEAL_MELANOMA_UP, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MYOD_01, MODULE_239, GOBP_NUCLEUS_ORGANIZATION, GATA1_01, E4F1_Q6

GO Biological Process (4): positive regulation of ATP-dependent activity (GO:0032781), protein localization to nucleus (GO:0034504), nuclear membrane organization (GO:0071763), protein localization to nuclear envelope (GO:0090435)

GO Molecular Function (5): ATPase activator activity (GO:0001671), lamin binding (GO:0005521), cytoskeletal protein binding (GO:0008092), ATPase binding (GO:0051117), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), nucleoplasm (GO:0005654), nuclear membrane (GO:0031965), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ATP-dependent activity	2
protein binding	2
nucleus	2
regulation of ATP-dependent activity	1
positive regulation of molecular function	1
protein localization to organelle	1
nuclear envelope organization	1
membrane organization	1
protein localization to nucleus	1
molecular function activator activity	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
nuclear lumen	1
nuclear envelope	1
organelle membrane	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOR1AIP1	TOR1A	O14656	773
TOR1AIP1	EMD	P50402	731
TOR1AIP1	TOR3A	Q9H497	628
TOR1AIP1	LMNB1	P20700	599
TOR1AIP1	LMNB2	Q03252	555
TOR1AIP1	TDRD5	Q8NAT2	533
TOR1AIP1	TOR2A	Q5JU69	532
TOR1AIP1	CEP350	Q5VT06	528
TOR1AIP1	TOR1B	O14657	502
TOR1AIP1	QSOX1	O00391	491
TOR1AIP1	SUN1	O94901	476
TOR1AIP1	ERMP1	Q7Z2K6	474
TOR1AIP1	ARL6IP1	Q15041	465
TOR1AIP1	COMMD2	Q86X83	453
TOR1AIP1	AGTRAP	Q6RW13	448

IntAct

143 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
KLHL15	TOR1AIP1	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
PPP1CA	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.570
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
Tor1aip1	CANX	psi-mi:“MI:0915”(physical association)	0.560
Mad2l1	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
PSME1	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.560
SNW1	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.560
BRWD1	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.560
AGGF1	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.560
ZNF296	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.560
SPATS1	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (344): TOR1AIP1 (Affinity Capture-MS), TOR1AIP1 (Affinity Capture-MS), TOR1AIP1 (Affinity Capture-MS), TOR1AIP1 (Affinity Capture-MS), TOR1AIP1 (Reconstituted Complex), TOR1AIP1 (Affinity Capture-Western), TOR1A (Affinity Capture-Western), TOR1AIP1 (Co-purification), TOR1AIP1 (Affinity Capture-MS), TOR1AIP1 (Affinity Capture-RNA), TOR1AIP1 (Affinity Capture-MS), TOR1AIP1 (Proximity Label-MS), TOR1AIP1 (Proximity Label-MS), TOR1AIP1 (Proximity Label-MS), TOR1AIP1 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A8T6P4, C0SPG1, C3VD30, F1N4E5, K7SGN7, O35144, O35253, O70240, O88406, O88566, Q15554, Q1XFL1, Q3ZC82, Q4KLH3, Q5HZN9, Q5JTV8, Q5PQX1, Q5R7A3, Q62315, Q68DK7, Q6P1H6, Q6PDM1, Q6PG95, Q6ZPF3, Q76N89, Q7T3T8, Q7T3T9, Q7T3U0, Q7TNY7, Q7TP65, Q7TSX9, Q80SU3, Q80VM8, Q86XL3, Q8IVF5, Q8K3I4

Diamond homologs: F1N4E5, Q5JTV8, Q5PQX1, Q5R7A3, Q6P752, Q8BYU6, Q8NFQ8, Q921T2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TOR1AIP1	“up-regulates activity”	VIM	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 150 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PD-L1(CD274) glycosylation and translocation to plasma membrane	5	24.7×	2e-04
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	6	19.2×	1e-04
RAF activation	5	16.0×	8e-04
Maturation of spike protein	6	15.2×	2e-04
Maturation of DENV proteins	6	12.1×	6e-04
Regulation of RAS by GAPs	6	11.1×	8e-04
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	10.9×	3e-03
Signaling by BRAF and RAF1 fusions	6	9.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein N-linked glycosylation	6	12.3×	4e-03
ERAD pathway	7	9.9×	4e-03
MAPK cascade	7	8.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

364 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	16
Uncertain significance	161
Likely benign	134
Benign	31

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
3023484	NM_015602.4(TOR1AIP1):c.583C>T (p.Arg195Ter)	Pathogenic
660593	NM_015602.4(TOR1AIP1):c.646G>T (p.Glu216Ter)	Pathogenic
862996	NM_015602.4(TOR1AIP1):c.763C>T (p.Gln255Ter)	Pathogenic
950989	NM_015602.4(TOR1AIP1):c.663del (p.Glu222fs)	Pathogenic
1466030	NM_015602.4(TOR1AIP1):c.739+1G>A	Likely pathogenic
2083769	NM_015602.4(TOR1AIP1):c.838+2T>A	Likely pathogenic
2636209	NM_015602.4(TOR1AIP1):c.610G>T (p.Glu204Ter)	Likely pathogenic
2981146	NM_015602.4(TOR1AIP1):c.907+1G>A	Likely pathogenic
3377574	NM_015602.4(TOR1AIP1):c.797-2A>G	Likely pathogenic
3603577	NM_015602.4(TOR1AIP1):c.476-1G>C	Likely pathogenic
3727645	NM_015602.4(TOR1AIP1):c.739+2T>C	Likely pathogenic
4749402	NM_015602.4(TOR1AIP1):c.797-1G>T	Likely pathogenic
4813827	NM_015602.4(TOR1AIP1):c.301_302del (p.Glu101fs)	Likely pathogenic
522870	NM_015602.4(TOR1AIP1):c.1427C>T (p.Ala476Val)	Likely pathogenic
643973	NM_015602.4(TOR1AIP1):c.906_907+5del	Likely pathogenic
644515	NM_015602.4(TOR1AIP1):c.553+1G>A	Likely pathogenic
804380	NM_015602.4(TOR1AIP1):c.961C>T (p.Arg321Ter)	Likely pathogenic
818045	NM_015602.4(TOR1AIP1):c.721del (p.Asp241fs)	Likely pathogenic
843154	NM_015602.4(TOR1AIP1):c.797-2A>T	Likely pathogenic
952016	NM_015602.4(TOR1AIP1):c.554-4_554-1delinsAC	Likely pathogenic

SpliceAI

1666 predictions. Top by Δscore:

Variant	Effect	Δscore
1:179884689:TA:T	acceptor_loss	1.0000
1:179884690:A:AG	acceptor_gain	1.0000
1:179884690:A:C	acceptor_loss	1.0000
1:179884690:AGAG:A	acceptor_gain	1.0000
1:179884691:G:GG	acceptor_gain	1.0000
1:179884691:GA:G	acceptor_gain	1.0000
1:179884691:GAGG:G	acceptor_gain	1.0000
1:179884691:GAGGA:G	acceptor_gain	1.0000
1:179884766:CCAGG:C	donor_loss	1.0000
1:179884767:CAGG:C	donor_loss	1.0000
1:179884768:AGGT:A	donor_loss	1.0000
1:179884769:GGTA:G	donor_loss	1.0000
1:179884770:G:C	donor_loss	1.0000
1:179884770:G:GG	donor_gain	1.0000
1:179901297:TTTAG:T	acceptor_loss	1.0000
1:179901299:TAG:T	acceptor_loss	1.0000
1:179901300:A:AG	acceptor_gain	1.0000
1:179901300:AG:A	acceptor_gain	1.0000
1:179901301:G:A	acceptor_gain	1.0000
1:179901301:G:GT	acceptor_gain	1.0000
1:179901301:GGA:G	acceptor_gain	1.0000
1:179901301:GGAGA:G	acceptor_gain	1.0000
1:179901385:GGAG:G	donor_gain	1.0000
1:179901386:G:GT	donor_gain	1.0000
1:179901386:GAG:G	donor_gain	1.0000
1:179901387:AGG:A	donor_loss	1.0000
1:179901388:GG:G	donor_loss	1.0000
1:179901389:G:C	donor_loss	1.0000
1:179901389:G:GG	donor_gain	1.0000
1:179901390:T:G	donor_loss	1.0000

AlphaMissense

3792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:179918168:T:A	W561R	0.997
1:179918168:T:C	W561R	0.997
1:179917776:C:A	A430D	0.995
1:179917994:T:C	F503L	0.995
1:179917996:C:A	F503L	0.995
1:179917996:C:G	F503L	0.995
1:179917727:G:C	A414P	0.994
1:179917893:T:C	F469S	0.994
1:179917914:C:A	A476D	0.994
1:179918022:T:A	V512D	0.994
1:179918170:G:C	W561C	0.994
1:179918170:G:T	W561C	0.994
1:179918175:G:C	R563P	0.994
1:179917646:T:A	W387R	0.993
1:179917646:T:C	W387R	0.993
1:179917648:G:C	W387C	0.993
1:179917648:G:T	W387C	0.993
1:179917763:A:C	S426R	0.993
1:179917765:T:A	S426R	0.993
1:179917765:T:G	S426R	0.993
1:179917881:T:C	L465P	0.993
1:179917974:G:A	C496Y	0.993
1:179917975:T:G	C496W	0.993
1:179918166:T:C	L560P	0.993
1:179918171:A:C	S562R	0.993
1:179918173:C:A	S562R	0.993
1:179918173:C:G	S562R	0.993
1:179918174:C:A	R563S	0.993
1:179917861:A:C	K458N	0.992
1:179917861:A:T	K458N	0.992

dbSNP variants (sampled 300 via entrez): RS1000080164 (1:179889792 C>G), RS1000089112 (1:179909646 C>T), RS1000139219 (1:179880474 T>A), RS1000289083 (1:179885487 G>C), RS1000329698 (1:179884099 G>A,T), RS1000391342 (1:179912836 A>G), RS1000425088 (1:179895569 C>G), RS1000490000 (1:179920302 T>A), RS1000549567 (1:179909474 A>G), RS1000574299 (1:179884320 CT>C,CTT), RS1000614894 (1:179919780 A>C), RS1000639535 (1:179885960 C>G,T), RS1000671558 (1:179914725 C>G,T), RS1000916823 (1:179901921 C>G), RS1001009717 (1:179891269 T>C)

Disease associations

OMIM: gene MIM:614512 | disease phenotypes: MIM:617072

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2Y	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
TOR1AIP1-related multisystem disorder	Definitive	AR
TOR1AIP1-related myopathy	Definitive	AR

Mondo (1): autosomal recessive limb-girdle muscular dystrophy type 2Y (MONDO:0014900)

Orphanet (1): TOR1AIP1-related limb-girdle muscular dystrophy (Orphanet:424261)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001324	Muscle weakness
HP:0002460	Distal muscle weakness
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003306	Spinal rigidity
HP:0003551	Difficulty climbing stairs
HP:0003557	Increased variability in muscle fiber diameter
HP:0003560	Muscular dystrophy
HP:0003621	Juvenile onset
HP:0003677	Slowly progressive
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0006466	Ankle flexion contracture
HP:0006682	Premature ventricular contraction
HP:0007181	Interosseus muscle atrophy
HP:0009697	Contracture of the distal interphalangeal joint of the fingers
HP:0025708	Early young adult onset
HP:0032359	Decreased forced expiratory flow 25-75%
HP:0034392	Joint contracture
HP:0100297	Increased endomysial connective tissue
HP:0100490	Camptodactyly of finger

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_371	Refractive error	3.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067329 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.53	Kd	293.1	nM	CHEMBL5653589
6.53	ED50	293.1	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149638: Binding affinity to human TOR1AIP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.2931	uM

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
methylselenic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Bortezomib	decreases expression	1
Sunitinib	increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression, affects cotreatment	1
Catechin	affects cotreatment, increases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652680	Binding	Binding affinity to human TOR1AIP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0SV	BIUi001-A	Induced pluripotent stem cell	Female
CVCL_A0SW	BIUi002-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments