TOR1B

Summary

TOR1B (torsin family 1 member B, HGNC:11995) is a protein-coding gene on chromosome 9q34.11, encoding Torsin-1B (O14657). May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins.

The protein encoded by this gene is an ATPase found primarily in the endoplasmic reticulum and nuclear envelope. This gene has a highly-similar neighboring gene, TOR1A, that encodes a protein that is likely to interact in a complex with this protein. Finally, this protein may act as a chaperone and play a role in maintaining the integrity of the nuclear envelope and endoplasmic reticulum. Several transcript variants, some protein-coding and others non-protein coding, have been found for this gene.

Source: NCBI Gene 27348 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_014506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11995
Approved symbol	TOR1B
Name	torsin family 1 member B
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	DQ1, MGC4386
Ensembl gene	ENSG00000136816
Ensembl biotype	protein_coding
OMIM	608050
Entrez	27348

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000259339, ENST00000427860, ENST00000486372, ENST00000488169, ENST00000931518

RefSeq mRNA: 3 — MANE Select: NM_014506 NM_001317893, NM_001317894, NM_014506

CCDS: CCDS6929

Canonical transcript exons

ENST00000259339 — 5 exons

Exon	Start	End
ENSE00000927272	129803184	129803411
ENSE00001052717	129809342	129811281
ENSE00001154538	129804073	129804338
ENSE00003529667	129808905	129809032
ENSE00003600018	129807188	129807363

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 91.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7771 / max 211.2762, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98959	15.8048	1808
98958	6.9606	1790
98960	0.0117	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	91.97	gold quality
colonic mucosa	UBERON:0000317	91.62	gold quality
rectum	UBERON:0001052	91.13	gold quality
monocyte	CL:0000576	90.43	gold quality
mononuclear cell	CL:0000842	90.30	gold quality
leukocyte	CL:0000738	90.29	gold quality
stromal cell of endometrium	CL:0002255	89.68	gold quality
decidua	UBERON:0002450	88.89	gold quality
cortical plate	UBERON:0005343	88.79	gold quality
ileal mucosa	UBERON:0000331	88.67	gold quality
granulocyte	CL:0000094	88.59	gold quality
endothelial cell	CL:0000115	88.51	gold quality
blood	UBERON:0000178	87.92	gold quality
islet of Langerhans	UBERON:0000006	87.85	gold quality
cerebellar hemisphere	UBERON:0002245	87.64	gold quality
cerebellar cortex	UBERON:0002129	87.55	gold quality
mucosa of transverse colon	UBERON:0004991	87.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.36	gold quality
palpebral conjunctiva	UBERON:0001812	87.06	gold quality
cartilage tissue	UBERON:0002418	87.03	gold quality
transverse colon	UBERON:0001157	86.99	gold quality
cerebellum	UBERON:0002037	86.43	gold quality
gall bladder	UBERON:0002110	86.16	gold quality
large intestine	UBERON:0000059	85.99	gold quality
colon	UBERON:0001155	85.89	gold quality
calcaneal tendon	UBERON:0003701	85.69	gold quality
right lobe of liver	UBERON:0001114	85.41	gold quality
descending thoracic aorta	UBERON:0002345	85.35	gold quality
jejunal mucosa	UBERON:0000399	85.24	gold quality
bone marrow	UBERON:0002371	85.15	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.00
E-MTAB-6386	no	436.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

65 targeting TOR1B, 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-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-766-3P	99.47	65.24	1811

Literature-anchored findings (GeneRIF, showing 4)

• torsinB is needed for developmental events occurring in the early postnatal phase and is necessary for functional activity throughout life (PMID:16938275)
• the induction of a conditional, dominant-negative TorsinB variant provokes a profound reorganization of the endomembrane system into foci containing double membrane structures that are derived from the ER. (PMID:24275647)
• TOR1B: a predictor of bone metastasis in breast cancer patients. (PMID:36707670)
• Prognostic implications of TOR1B expression across cancer types: a focus on basal-like breast cancer and cellular adaptations to hypoxia. (PMID:38842687)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	tor1l3	ENSDARG00000026895
danio_rerio	tor1l1	ENSDARG00000055856
danio_rerio	tor1	ENSDARG00000077950
danio_rerio	tor1l2	ENSDARG00000090741
mus_musculus	Tor1b	ENSMUSG00000026848
rattus_norvegicus	Tor1b	ENSRNOG00000006435
drosophila_melanogaster	Torsin	FBGN0025615
caenorhabditis_elegans		WBGENE00003870
caenorhabditis_elegans		WBGENE00006597
caenorhabditis_elegans		WBGENE00006598

Paralogs (4): TOR1A (ENSG00000136827), TOR2A (ENSG00000160404), TOR3A (ENSG00000186283), TOR4A (ENSG00000198113)

Protein

Protein identifiers

Torsin-1B — O14657 (reviewed: O14657)

Alternative names: Torsin ATPase-1B, Torsin family 1 member B

All UniProt accessions (2): O14657, H0Y7C8

UniProt curated annotations — full annotation on UniProt →

Function. May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins. Plays a role in non-neural cells nuclear envelope and endoplasmic reticulum integrity. May have a redundant function with TOR1A in non-neural tissues.

Subunit / interactions. Homohexamer. Interacts with TOR1A; the interaction may be specific of neural tissues. Interacts with TOR1AIP1; TOR1AIP1 is required for TOR1B location on the nuclear membrane. Interacts (ATP-bound) with TOR1AIP2; important for endoplasmic reticulum integrity.

Subcellular location. Endoplasmic reticulum lumen. Nucleus membrane.

Tissue specificity. Widely expressed with low levels in brain.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the ClpA/ClpB family. Torsin subfamily.

RefSeq proteins (3): NP_001304822, NP_001304823, NP_055321* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010448	Torsin	Family
IPR017378	Torsin_1/2	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR049337	TOR1A_C	Domain

Pfam: PF06309, PF21376

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (10 total): mutagenesis site 4, glycosylation site 2, signal peptide 1, chain 1, binding site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14657-F1	85.67	0.67

Functional residue map

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

Ligand- & substrate-binding residues (1): 109–116

Glycosylation sites (2): 64, 165

Mutagenesis-validated functional residues (4):

Position	Phenotype
178	loss of atpase activity. produces sinusoidal endoplasmic reticulum structures where it accumulates. highly enhances inte
334–336	highly reduces atpase activity induced by tor1aip2.
334–336	decreases interaction with tor1aip2.
335	no effect on interaction with tor1aip2.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis

MSigDB gene sets: 191 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_NUCLEUS_ORGANIZATION, MODULE_301, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, SCHLOSSER_SERUM_RESPONSE_DN, DOUGLAS_BMI1_TARGETS_DN, MODULE_544, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_ENVELOPE_ORGANIZATION, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, MODULE_188, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, MILI_PSEUDOPODIA_CHEMOTAXIS_DN

GO Biological Process (5): response to unfolded protein (GO:0006986), endoplasmic reticulum organization (GO:0007029), protein localization to nucleus (GO:0034504), nuclear membrane organization (GO:0071763), obsolete chaperone cofactor-dependent protein refolding (GO:0051085)

GO Molecular Function (7): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), kinesin binding (GO:0019894), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), nuclear membrane (GO:0031965), extracellular exosome (GO:0070062), nucleus (GO:0005634), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleus	2
endomembrane system	2
intracellular membrane-bounded organelle	2
response to topologically incorrect protein	1
organelle organization	1
endomembrane system organization	1
protein localization to organelle	1
nuclear envelope organization	1
membrane organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
cytoskeletal protein binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
organelle envelope	1
cytoplasm	1
endoplasmic reticulum	1
intracellular organelle lumen	1
nuclear envelope	1
organelle membrane	1
extracellular vesicle	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

830 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOR1B	TOR1AIP2	Q8NFQ8	870
TOR1B	HLA-DQB1	P01917	786
TOR1B	Q5Y7H0	Q5Y7H0	778
TOR1B	TNFRSF25	P78507	769
TOR1B	TNFRSF10A	O00220	729
TOR1B	HLA-DPB1	P01916	708
TOR1B	DYNLT1	P63172	667
TOR1B	TNFRSF21	O75509	645
TOR1B	WDR11	Q9BZH6	593
TOR1B	HLA-B	P01889	578
TOR1B	HLA-DRB1	P01911	571
TOR1B	MBP	P02686	537
TOR1B	HLA-A	P01891	506
TOR1B	TOR1AIP1	Q5JTV8	502
TOR1B	CACNA1S	Q13698	497

IntAct

75 interactions, top by confidence:

A	B	Type	Score
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
GIMAP2	TOR1B	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
TOR1B	CLGN	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
TOR1A	TOR1B	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
	TOR1B	psi-mi:“MI:0882”(atpase reaction)	0.440
TOR1AIP1	TOR1B	psi-mi:“MI:0915”(physical association)	0.400
TOR1B	CFTR	psi-mi:“MI:0915”(physical association)	0.370
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
ADPGK	TOR1B	psi-mi:“MI:0914”(association)	0.350
TOR1B	LMAN2L	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): TOR1B (Affinity Capture-Western), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), GHITM (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), LMAN2L (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS), TOR1B (Affinity Capture-MS)

ESM2 similar proteins: A0JPQ9, O14657, O14672, O19015, O35598, P09958, P16098, P23188, P23377, P58780, P82993, Q01458, Q01460, Q08169, Q0JJD4, Q10741, Q10743, Q10RB4, Q1L8D2, Q28193, Q29LW1, Q29NU5, Q4V8H8, Q58D55, Q5EAB4, Q5GF25, Q5RFF6, Q66IL0, Q68EX9, Q6NXH2, Q6ZJJ0, Q7SYK0, Q7Z1Z1, Q8BH64, Q8MLZ7, Q8MX31, Q8MX32, Q8MX40, Q8T0R7, Q922Q9

Diamond homologs: A4FUH1, O14656, O14657, O77277, P0C7W1, P0C7W2, P0C7W3, Q5JU69, Q5M936, Q60HG2, Q68F68, Q68G38, Q6AYR4, Q8N2E6, Q8R1J9, Q95NU5, Q9ER38, Q9ER39, Q9ER41, Q9ERA9, Q9H497, Q568B8, Q8BH02

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	7	18.6×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1012 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129803410:GG:G	donor_gain	1.0000
9:129803411:GG:G	donor_gain	1.0000
9:129803411:GGTAC:G	donor_loss	1.0000
9:129803412:G:GG	donor_gain	1.0000
9:129803412:GTACG:G	donor_loss	1.0000
9:129804056:T:TA	acceptor_gain	1.0000
9:129804057:G:A	acceptor_gain	1.0000
9:129804123:G:GT	donor_gain	1.0000
9:129804155:G:GT	donor_gain	1.0000
9:129807175:AT:A	acceptor_gain	1.0000
9:129807175:ATG:A	acceptor_gain	1.0000
9:129807176:T:TA	acceptor_gain	1.0000
9:129807177:G:A	acceptor_gain	1.0000
9:129808893:T:A	acceptor_gain	1.0000
9:129808894:G:A	acceptor_gain	1.0000
9:129808897:A:AG	acceptor_gain	1.0000
9:129808898:A:G	acceptor_gain	1.0000
9:129803407:TTCGG:T	donor_gain	0.9900
9:129804156:A:T	donor_gain	0.9900
9:129807101:A:AG	acceptor_gain	0.9900
9:129807102:G:GG	acceptor_gain	0.9900
9:129807175:A:AG	acceptor_gain	0.9900
9:129807176:T:G	acceptor_gain	0.9900
9:129807180:T:A	acceptor_gain	0.9900
9:129807246:T:G	acceptor_gain	0.9900
9:129808951:C:CA	acceptor_gain	0.9900
9:129808952:G:A	acceptor_gain	0.9900
9:129809028:ACACA:A	donor_gain	0.9900
9:129809029:CACA:C	donor_gain	0.9900
9:129809031:CA:C	donor_gain	0.9900

AlphaMissense

2210 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129809548:T:A	C326S	0.998
9:129809549:G:C	C326S	0.998
9:129804216:A:C	K115Q	0.997
9:129804217:A:T	K115M	0.997
9:129804218:G:C	K115N	0.997
9:129804218:G:T	K115N	0.997
9:129809432:G:A	C287Y	0.997
9:129809433:T:G	C287W	0.997
9:129809553:G:C	K327N	0.997
9:129809553:G:T	K327N	0.997
9:129804199:G:A	G109D	0.996
9:129804208:G:A	G112D	0.996
9:129804214:G:A	G114D	0.996
9:129809431:T:A	C287S	0.996
9:129809431:T:C	C287R	0.996
9:129809432:G:C	C287S	0.996
9:129809545:G:C	G325R	0.996
9:129809548:T:C	C326R	0.996
9:129809549:G:A	C326Y	0.996
9:129804198:G:C	G109R	0.995
9:129804217:A:C	K115T	0.995
9:129804221:T:A	N116K	0.995
9:129804221:T:G	N116K	0.995
9:129808925:T:A	I221K	0.995
9:129809545:G:T	G325C	0.995
9:129804106:G:A	G78E	0.994
9:129804207:G:C	G112R	0.994
9:129809432:G:T	C287F	0.994
9:129804214:G:T	G114V	0.993
9:129804228:A:C	S119R	0.993

dbSNP variants (sampled 300 via entrez): RS1000263092 (9:129803601 G>T), RS1000868352 (9:129805031 G>A,C,T), RS1001037507 (9:129804478 A>G), RS1001151534 (9:129805245 G>A,C,T), RS1001345243 (9:129811048 C>A,G,T), RS1001461214 (9:129805641 T>G), RS1001492043 (9:129806077 T>A,C,G), RS1001825921 (9:129803802 G>T), RS1001883569 (9:129804906 AG>A,AGG), RS1002496280 (9:129806142 C>G,T), RS1002716608 (9:129809146 A>G), RS1002831608 (9:129809556 T>A,C), RS1003535796 (9:129801842 A>G), RS1003909676 (9:129807685 AAAAT>A), RS1003972005 (9:129802087 C>T)

Disease associations

OMIM: gene MIM:608050 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90011898_117	Alanine aminotransferase levels	2.000000e-08
GCST90013405_29	Liver enzyme levels (alanine transaminase)	1.000000e-15
GCST90016673_11	Percent liver fat	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010821	liver fat measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Tretinoin	increases expression	2
Valproic Acid	increases expression, affects expression	2
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
tamibarotene	increases expression	1
CGP 52608	affects binding, increases reaction	1
hexabrominated diphenyl ether 153	increases expression	1
(+)-JQ1 compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzene	increases expression	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Nickel	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Zinc	affects cotreatment, increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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