TOR3A

Summary

TOR3A (torsin family 3 member A, HGNC:11997) is a protein-coding gene on chromosome 1q25.2, encoding Torsin-3A (Q9H497).

Enables ATP hydrolysis activity. Located in endoplasmic reticulum lumen.

Source: NCBI Gene 64222 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_022371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11997
Approved symbol	TOR3A
Name	torsin family 3 member A
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22345, ADIR2
Ensembl gene	ENSG00000186283
Ensembl biotype	protein_coding
OMIM	607555
Entrez	64222

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000352445, ENST00000367625, ENST00000367627, ENST00000447595, ENST00000472001, ENST00000483887, ENST00000495145, ENST00000868391, ENST00000868392, ENST00000868393, ENST00000868394, ENST00000936957, ENST00000943766, ENST00000943767

RefSeq mRNA: 1 — MANE Select: NM_022371 NM_022371

CCDS: CCDS1329

Canonical transcript exons

ENST00000367627 — 6 exons

Exon	Start	End
ENSE00001603586	179094968	179095996
ENSE00001682327	179082070	179082387
ENSE00002082836	179094093	179094217
ENSE00003522820	179087911	179088089
ENSE00003571552	179082940	179083053
ENSE00003665377	179085628	179085893

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 95.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8595 / max 215.6569, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6900	15.4078	1804
6901	4.0959	1530
6899	0.3558	117

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.97	gold quality
granulocyte	CL:0000094	93.27	gold quality
lymph node	UBERON:0000029	92.98	gold quality
monocyte	CL:0000576	92.81	gold quality
mononuclear cell	CL:0000842	92.50	gold quality
leukocyte	CL:0000738	92.48	gold quality
spleen	UBERON:0002106	92.45	gold quality
mucosa of transverse colon	UBERON:0004991	91.43	gold quality
vermiform appendix	UBERON:0001154	91.20	gold quality
islet of Langerhans	UBERON:0000006	90.72	gold quality
caecum	UBERON:0001153	90.09	gold quality
rectum	UBERON:0001052	90.01	gold quality
epithelium of nasopharynx	UBERON:0001951	89.87	gold quality
bone marrow cell	CL:0002092	89.72	gold quality
secondary oocyte	CL:0000655	89.67	gold quality
buccal mucosa cell	CL:0002336	89.67	silver quality
small intestine Peyer’s patch	UBERON:0003454	89.59	gold quality
body of stomach	UBERON:0001161	89.24	gold quality
transverse colon	UBERON:0001157	89.23	gold quality
gastrocnemius	UBERON:0001388	89.10	gold quality
left uterine tube	UBERON:0001303	89.08	gold quality
body of pancreas	UBERON:0001150	88.87	gold quality
minor salivary gland	UBERON:0001830	88.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.87	gold quality
right lobe of liver	UBERON:0001114	88.75	gold quality
adenohypophysis	UBERON:0002196	88.71	gold quality
saliva-secreting gland	UBERON:0001044	88.61	gold quality
pancreas	UBERON:0001264	88.47	gold quality
small intestine	UBERON:0002108	88.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-88	yes	14.39
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting TOR3A, 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-8068	99.98	73.85	2376
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-6859-3P	97.26	64.69	428

Literature-anchored findings (GeneRIF, showing 1)

• Our study identified five new loci associated with VKH susceptibility and identified a functional variant (lnc-TOR3A-1:1/rs3829794) that confers risk for VKH, which is possibly mediated by modulating gene expression, proliferation of lymphocytes, and regulation of anti-inflammatory cytokine production. (PMID:31747682)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tor3a	ENSDARG00000079308
mus_musculus	Tor3a	ENSMUSG00000060519
rattus_norvegicus	Tor3a	ENSRNOG00000004307
drosophila_melanogaster	Torsin	FBGN0025615
caenorhabditis_elegans		WBGENE00003870
caenorhabditis_elegans		WBGENE00006597
caenorhabditis_elegans		WBGENE00006598

Paralogs (4): TOR1B (ENSG00000136816), TOR1A (ENSG00000136827), TOR2A (ENSG00000160404), TOR4A (ENSG00000198113)

Protein

Protein identifiers

Torsin-3A — Q9H497 (reviewed: Q9H497)

Alternative names: ATP-dependent interferon-responsive protein, Torsin family 3 member A

All UniProt accessions (4): Q9H497, F2Z3J4, Q5W0C6, Q5W0C9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. May not form homohexamers.

Subcellular location. Cytoplasm. Endoplasmic reticulum lumen.

Tissue specificity. Ubiquitously expressed. Highest expression in stomach, salivary glands and lymph nodes. Isoform 2 is expressed in placenta.

Post-translational modifications. N-glycosylated.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H497-1	1, ADIR1	yes
Q9H497-2	2, ADIR2
Q9H497-3	3

RefSeq proteins (1): NP_071766* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010448	Torsin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR049337	TOR1A_C	Domain

Pfam: PF06309, PF21376

UniProt features (10 total): splice variant 3, signal peptide 1, chain 1, binding site 1, glycosylation site 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H497-F1	78.24	0.50

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): 167–174

Glycosylation sites (1): 122

Mutagenesis-validated functional residues (1):

Position	Phenotype
236	no effect on subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 245 (showing top): ELVIDGE_HYPOXIA_DN, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GTGCCTT_MIR506, WEI_MYCN_TARGETS_WITH_E_BOX, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, COATES_MACROPHAGE_M1_VS_M2_UP, CAIRO_HEPATOBLASTOMA_UP, BOYAULT_LIVER_CANCER_SUBCLASS_G12_UP, TGCCTTA_MIR124A, GOCC_NUCLEAR_ENVELOPE

GO Biological Process (0):

GO Molecular Function (3): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166)

GO Cellular Component (5): nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleus	1
organelle envelope	1
cytoplasm	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
extracellular vesicle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOR3A	TOR1AIP2	Q8NFQ8	673
TOR3A	TOR1AIP1	Q5JTV8	628
TOR3A	RFT1	Q96AA3	625
TOR3A	TDRD5	Q8NAT2	508
TOR3A	CEP350	Q5VT06	504
TOR3A	HMSD	A8MTL9	478
TOR3A	QSOX1	O00391	472
TOR3A	MRPS18A	Q9NVS2	458
TOR3A	SOAT1	P35610	456
TOR3A	OLFML2B	Q68BL8	447
TOR3A	SPAG4	Q9NPE6	442
TOR3A	IFNA2	P01563	424
TOR3A	IFNA17	P01571	424
TOR3A	SEC16B	Q96JE7	423
TOR3A	NPHS2	Q9NP85	418

IntAct

65 interactions, top by confidence:

A	B	Type	Score
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
WNT16	WNT11	psi-mi:“MI:0914”(association)	0.530
DNASE2B	ARSA	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
	TOR1AIP2	psi-mi:“MI:0882”(atpase reaction)	0.440
FOXS1	DDX39A	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TMPRSS3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ANGPT4	POTEF	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
IGHD	POTEF	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PRG2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
ARSG	YDJC	psi-mi:“MI:0914”(association)	0.350
ACRBP	MYO9A	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
PRSS50	PRSS46P	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
F9	APBB1	psi-mi:“MI:0914”(association)	0.350
IGFL3	CBX4	psi-mi:“MI:0914”(association)	0.350
LYPD4	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
NOG	TCAF2	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
ADAM33	ADAM10	psi-mi:“MI:0914”(association)	0.350
LGI1	APAF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (112): TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), TMEM43 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), WRB (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), TOR3A (Affinity Capture-MS)

ESM2 similar proteins: A0A4Z3, A1Y9I9, A4FUH1, B6CZ46, B6CZ56, B6CZ62, D3ZNQ3, G3V9Q9, O43505, O60512, O60909, O94766, P14616, P14617, P58158, Q09326, Q10469, Q2NKH9, Q2YDM8, Q3V1N9, Q3V5L5, Q4R5T7, Q5EA01, Q5EB73, Q5JU69, Q5M936, Q5NVN3, Q5R4S2, Q5R868, Q5YB40, Q5ZLK4, Q64716, Q6AYR4, Q765H6, Q7Z4J2, Q8BGT9, Q8BWP8, Q8IXK2, Q8NCL4, Q8R1J9

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

837 predictions. Top by Δscore:

Variant	Effect	Δscore
1:179085623:CTTA:C	acceptor_loss	1.0000
1:179085625:TA:T	acceptor_loss	1.0000
1:179085626:A:AG	acceptor_gain	1.0000
1:179085627:G:GG	acceptor_gain	1.0000
1:179085839:G:GT	donor_gain	1.0000
1:179085891:AAG:A	donor_loss	1.0000
1:179085893:GGTGA:G	donor_loss	1.0000
1:179085894:GT:G	donor_loss	1.0000
1:179088054:GGC:G	donor_gain	1.0000
1:179088055:GC:G	donor_gain	1.0000
1:179088056:C:G	donor_gain	1.0000
1:179094091:A:AG	acceptor_gain	1.0000
1:179094092:G:GT	acceptor_gain	1.0000
1:179094092:GT:G	acceptor_gain	1.0000
1:179094092:GTA:G	acceptor_gain	1.0000
1:179094092:GTAA:G	acceptor_gain	1.0000
1:179094092:GTAAT:G	acceptor_gain	1.0000
1:179094094:A:AG	acceptor_gain	1.0000
1:179094213:CATAG:C	donor_gain	1.0000
1:179094214:ATAG:A	donor_gain	1.0000
1:179094214:ATAGG:A	donor_gain	1.0000
1:179094215:TAG:T	donor_gain	1.0000
1:179094215:TAGGT:T	donor_gain	1.0000
1:179094216:AG:A	donor_gain	1.0000
1:179094217:GG:G	donor_gain	1.0000
1:179094217:GGT:G	donor_gain	1.0000
1:179094217:GGTG:G	donor_loss	1.0000
1:179094218:G:GC	donor_loss	1.0000
1:179094218:G:GG	donor_gain	1.0000
1:179094218:GTG:G	donor_gain	1.0000

AlphaMissense

2599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:179095027:T:C	F335L	0.955
1:179095029:C:A	F335L	0.955
1:179095029:C:G	F335L	0.955
1:179085773:G:C	K173N	0.952
1:179085773:G:T	K173N	0.952
1:179085665:G:C	Q137H	0.946
1:179085665:G:T	Q137H	0.946
1:179095182:G:C	K386N	0.944
1:179095182:G:T	K386N	0.944
1:179085861:T:C	F203L	0.941
1:179085863:T:A	F203L	0.941
1:179085863:T:G	F203L	0.941
1:179085772:A:C	K173T	0.938
1:179095162:T:C	F380L	0.936
1:179095164:T:A	F380L	0.936
1:179095164:T:G	F380L	0.936
1:179085657:C:G	H135D	0.933
1:179085661:G:T	G136V	0.931
1:179095060:T:A	C346S	0.930
1:179095061:G:C	C346S	0.930
1:179095177:T:A	C385S	0.930
1:179095178:G:C	C385S	0.930
1:179085769:G:A	G172D	0.929
1:179085771:A:C	K173Q	0.928
1:179085769:G:T	G172V	0.927
1:179085772:A:T	K173M	0.920
1:179095067:G:C	R348P	0.920
1:179085643:T:C	L130P	0.912
1:179085754:G:A	G167D	0.912
1:179087950:T:A	C227S	0.908

dbSNP variants (sampled 300 via entrez): RS1000138208 (1:179083257 A>G), RS1000199195 (1:179084969 A>G), RS1000229152 (1:179089149 C>T), RS1000299036 (1:179083595 G>A,C,T), RS1000479552 (1:179083652 G>C), RS1000606088 (1:179086770 T>C), RS1000883439 (1:179090128 G>A,T), RS1001132202 (1:179092836 T>C), RS1001185006 (1:179096488 T>G), RS1001260826 (1:179090828 T>C), RS1001331085 (1:179080150 T>A), RS1001564632 (1:179081426 C>T), RS1001760032 (1:179082279 C>A,G,T), RS1001820269 (1:179086103 C>T), RS1002099916 (1:179087391 G>A)

Disease associations

OMIM: gene MIM:607555 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
bisphenol A	decreases expression, affects cotreatment, increases methylation	2
Cisplatin	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
propionaldehyde	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
nabiximols	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, increases expression	1
Copper	decreases expression, affects binding	1
Diazinon	increases methylation	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Oxygen	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2JC	Abcam HeLa TOR3A KO	Cancer cell line	Female

Clinical trials (associated diseases)

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