TOR4A

Summary

TOR4A (torsin family 4 member A, HGNC:25981) is a protein-coding gene on chromosome 9q34.3, encoding Torsin-4A (Q9NXH8).

Predicted to enable ATP binding activity and ATP hydrolysis activity. Predicted to be located in extracellular region and platelet alpha granule lumen. Predicted to be active in endoplasmic reticulum lumen and nuclear envelope.

Source: NCBI Gene 54863 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_017723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25981
Approved symbol	TOR4A
Name	torsin family 4 member A
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20245
Ensembl gene	ENSG00000198113
Ensembl biotype	protein_coding
Entrez	54863

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000357503, ENST00000919145, ENST00000964280, ENST00000964281

RefSeq mRNA: 1 — MANE Select: NM_017723 NM_017723

CCDS: CCDS7041

Canonical transcript exons

ENST00000357503 — 2 exons

Exon	Start	End
ENSE00001423277	137278653	137282641
ENSE00001429799	137277726	137277907

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 92.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2428 / max 98.7192, expressed in 1444 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99691	10.8286	1407
99693	1.8080	715
99692	1.1746	671
99694	0.4316	244

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.02	gold quality
mucosa of transverse colon	UBERON:0004991	86.48	gold quality
granulocyte	CL:0000094	85.68	gold quality
apex of heart	UBERON:0002098	85.35	gold quality
stromal cell of endometrium	CL:0002255	85.09	gold quality
monocyte	CL:0000576	84.53	gold quality
mononuclear cell	CL:0000842	84.35	gold quality
leukocyte	CL:0000738	84.34	gold quality
blood	UBERON:0000178	82.25	gold quality
pancreatic ductal cell	CL:0002079	82.13	silver quality
heart left ventricle	UBERON:0002084	80.71	gold quality
tendon of biceps brachii	UBERON:0008188	80.47	silver quality
cardiac ventricle	UBERON:0002082	80.34	gold quality
right lung	UBERON:0002167	79.77	gold quality
transverse colon	UBERON:0001157	79.73	gold quality
ileal mucosa	UBERON:0000331	79.72	gold quality
spleen	UBERON:0002106	79.29	gold quality
body of stomach	UBERON:0001161	79.26	gold quality
ascending aorta	UBERON:0001496	78.74	gold quality
thoracic aorta	UBERON:0001515	78.53	gold quality
upper lobe of left lung	UBERON:0008952	77.99	gold quality
lower esophagus mucosa	UBERON:0035834	77.33	gold quality
metanephros cortex	UBERON:0010533	77.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.04	gold quality
upper lobe of lung	UBERON:0008948	76.96	gold quality
heart right ventricle	UBERON:0002080	76.84	gold quality
decidua	UBERON:0002450	76.59	gold quality
stomach	UBERON:0000945	76.26	gold quality
descending thoracic aorta	UBERON:0002345	76.19	gold quality
colonic mucosa	UBERON:0000317	75.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting TOR4A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-363-5P	99.46	64.51	1015

Literature-anchored findings (GeneRIF, showing 1)

• Delta and Notch-like epidermal growth factor-related receptor suppresses human glioma growth by inhibiting oncogene TOR4A. (PMID:36204885)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	tor4aa	ENSDARG00000010145
danio_rerio	tor4ab	ENSDARG00000091169
mus_musculus	Tor4a	ENSMUSG00000059555
rattus_norvegicus	Tor4a	ENSRNOG00000009369
drosophila_melanogaster	Torsin	FBGN0025615
caenorhabditis_elegans		WBGENE00003870
caenorhabditis_elegans		WBGENE00006597
caenorhabditis_elegans		WBGENE00006598

Paralogs (4): TOR1B (ENSG00000136816), TOR1A (ENSG00000136827), TOR2A (ENSG00000160404), TOR3A (ENSG00000186283)

Protein

Protein identifiers

Torsin-4A — Q9NXH8 (reviewed: Q9NXH8)

Alternative names: Torsin family 4 member A

All UniProt accessions (1): Q9NXH8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

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

RefSeq proteins (1): NP_060193* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR010448	Torsin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF06309

UniProt features (9 total): modified residue 4, chain 1, transmembrane region 1, region of interest 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXH8-F1	79.35	0.54

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): 194–201

Post-translational modifications (4): 63, 81, 89, 106

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 123 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, MODULE_255, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, MODULE_317, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, TGANTCA_AP1_C, P300_01, GOCC_NUCLEAR_ENVELOPE, GOCC_PLATELET_ALPHA_GRANULE, GOCC_SECRETORY_VESICLE, NAKAMURA_METASTASIS, GOCC_VESICLE_LUMEN, GOCC_PLATELET_ALPHA_GRANULE_LUMEN, GOCC_ENDOPLASMIC_RETICULUM_LUMEN

GO Biological Process (0):

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

GO Cellular Component (7): extracellular region (GO:0005576), nuclear envelope (GO:0005635), endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020), platelet alpha granule lumen (GO:0031093), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
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
endomembrane system	1
organelle envelope	1
endoplasmic reticulum	1
intracellular organelle lumen	1
platelet alpha granule	1
secretory granule lumen	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOR4A	PCYT2	Q99447	537
TOR4A	TMEM59L	Q9UK28	522
TOR4A	ADISSP	Q9GZN8	518
TOR4A	CPNE1	Q99829	508
TOR4A	JCAD	Q9P266	490
TOR4A	PDLIM2	Q96JY6	488
TOR4A	PTPN23	Q9H3S7	466
TOR4A	SUMF1	Q8NBK3	452
TOR4A	TOR1AIP2	Q8NFQ8	439
TOR4A	SPART	Q8N0X7	436
TOR4A	RLIG1	Q8N999	410
TOR4A	PSMF1	Q92530	383
TOR4A	TCAF1	Q9Y4C2	376
TOR4A	RHEX	Q6ZWK4	359
TOR4A	ATG3	Q9NT62	356

IntAct

45 interactions, top by confidence:

A	B	Type	Score
CDH1	CTNND1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
ENPP6	CRLF3	psi-mi:“MI:0914”(association)	0.530
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
E7	AP2A1	psi-mi:“MI:0914”(association)	0.350
TK	AP3B1	psi-mi:“MI:0914”(association)	0.350
	IPO5	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
BGLF3.5	SEC16A	psi-mi:“MI:0914”(association)	0.350
BFRF1A	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
AKAP10	HAX1	psi-mi:“MI:0914”(association)	0.350
MYC	RAB29	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
TTMP	NBAS	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): TOR4A (Affinity Capture-MS), TOR4A (Affinity Capture-MS), TOR4A (Affinity Capture-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Proximity Label-MS), TOR4A (Affinity Capture-MS)

ESM2 similar proteins: A2WX64, A2X933, A2XFT5, A2XFT6, A2XVC2, A2YH25, A2ZF66, A2ZHL0, A2ZI32, A2ZI41, B9FCV3, B9FKP6, C7J0P3, P06024, P09758, P17471, P30816, P52377, Q08101, Q0D3C8, Q10MK2, Q16842, Q2QXM3, Q2QXP0, Q2QYF3, Q2R2W8, Q4ADV8, Q53JI9, Q5CAZ6, Q5Z8N6, Q69XK5, Q6P768, Q6Z3Y6, Q6Z5M3, Q6ZFH6, Q6ZI01, Q75BD5, Q7FA29, Q7XTB2, Q8CG64

Diamond homologs: P46694, P46695, Q0IHC5, Q3KQ18, Q568B8, Q5BKJ7, Q7YR42, Q8BH02, Q9NXH8, P0C7W2, P0C7W3, P0C7W1, Q8N2E6, Q8R1J9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

147 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137277869:C:T	donor_gain	0.9800
9:137278417:G:T	donor_gain	0.9800
9:137278417:G:GT	donor_gain	0.9700
9:137277884:C:G	donor_gain	0.9600
9:137278650:CAGGG:C	acceptor_gain	0.9600
9:137278651:AGGGA:A	acceptor_gain	0.9600
9:137278652:GGGAG:G	acceptor_gain	0.9600
9:137277905:CAGGT:C	donor_loss	0.9500
9:137277906:AG:A	donor_loss	0.9500
9:137277908:G:GA	donor_loss	0.9500
9:137277909:T:A	donor_loss	0.9500
9:137278651:AG:A	acceptor_gain	0.9500
9:137278652:GG:G	acceptor_gain	0.9500
9:137277890:G:T	donor_gain	0.9400
9:137278652:GGGA:G	acceptor_gain	0.9400
9:137277792:G:GT	donor_gain	0.9300
9:137278370:A:G	donor_gain	0.9200
9:137279937:G:GA	donor_gain	0.9000
9:137278350:G:GT	donor_gain	0.8900
9:137278647:TTGCA:T	acceptor_loss	0.8900
9:137278648:TGCAG:T	acceptor_loss	0.8900
9:137278649:GCAG:G	acceptor_loss	0.8900
9:137278650:CAGG:C	acceptor_loss	0.8900
9:137278651:A:AG	acceptor_gain	0.8900
9:137278652:G:GC	acceptor_loss	0.8900
9:137278652:G:GG	acceptor_gain	0.8900
9:137279936:T:TA	donor_gain	0.8800
9:137278651:AGG:A	acceptor_gain	0.8600
9:137278652:GGG:G	acceptor_gain	0.8600
9:137278430:A:G	donor_gain	0.8500

AlphaMissense

2697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137279926:T:A	C413S	0.996
9:137279927:G:C	C413S	0.996
9:137279810:G:A	C374Y	0.995
9:137279811:C:G	C374W	0.995
9:137279809:T:A	C374S	0.994
9:137279810:G:C	C374S	0.994
9:137279269:G:T	G194W	0.993
9:137279270:G:A	G194E	0.993
9:137279927:G:A	C413Y	0.993
9:137279285:G:T	G199V	0.992
9:137279810:G:T	C374F	0.992
9:137279285:G:A	G199D	0.991
9:137279289:G:C	K200N	0.991
9:137279289:G:T	K200N	0.991
9:137279809:T:C	C374R	0.991
9:137279923:G:T	G412C	0.991
9:137279924:G:T	G412V	0.989
9:137279080:G:C	G131R	0.988
9:137279269:G:A	G194R	0.988
9:137279269:G:C	G194R	0.988
9:137279813:T:C	F375S	0.988
9:137279928:C:G	C413W	0.988
9:137279109:C:A	N140K	0.987
9:137279109:C:G	N140K	0.987
9:137279159:T:C	L157P	0.987
9:137279290:A:C	S201R	0.987
9:137279292:C:A	S201R	0.987
9:137279292:C:G	S201R	0.987
9:137279924:G:A	G412D	0.987
9:137279926:T:C	C413R	0.987

dbSNP variants (sampled 300 via entrez): RS1000122647 (9:137277492 C>A,G,T), RS1000534987 (9:137278140 T>C), RS1000685727 (9:137281177 C>T), RS1001155380 (9:137276110 C>T), RS1001369961 (9:137281002 G>A), RS1001408666 (9:137281340 C>T), RS1001813917 (9:137281568 G>C), RS1001960975 (9:137276048 G>A,T), RS1002252528 (9:137277205 G>A,C), RS1002388796 (9:137282746 C>A,T), RS1002605213 (9:137277002 A>C,G), RS1003099524 (9:137280414 A>G), RS1003767127 (9:137279631 C>T), RS1004478613 (9:137275773 C>T), RS1004746675 (9:137281613 C>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:614959, MIM:615005, MIM:610253

GenCC curated gene-disease

Mondo (3): developmental and epileptic encephalopathy, 14 (MONDO:0013989), autosomal dominant nocturnal frontal lobe epilepsy 5 (MONDO:0014002), Kleefstra syndrome 1 (MONDO:0027407)

Orphanet (3): Kleefstra syndrome (Orphanet:261494), Epilepsy of infancy with migrating focal seizures (Orphanet:293181), Sleep-related hypermotor epilepsy (Orphanet:98784)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006976_132	Macular thickness	3.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563043	Kleefstra Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Valproic Acid	affects expression, decreases expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression, affects expression	2
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	2
aristolochic acid I	increases expression	1
propylparaben	increases expression	1
lead acetate	increases expression	1
kojic acid	decreases expression	1
methylparaben	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ferrous chloride	decreases expression	1
cupric chloride	increases expression	1
perfluorodecanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
prothioconazole	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	decreases expression	1
Vorinostat	decreases expression, affects cotreatment	1
Arbutin	decreases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Dexamethasone	increases expression, decreases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Indomethacin	decreases expression, affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07600736	PHASE2	RECRUITING	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of ABS-1230 in Pediatric Participants With KCNT1-related Epilepsy
NCT07156201	PHASE1	RECRUITING	A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of ABS-1230 Given Orally Compared With Placebo in Healthy Participants Aged 18 to 55 Years
NCT04924153	Not specified	COMPLETED	A Natural History Study of Participants With Potassium Sodium-Activated Channel Subfamily T Member 1 (KCNT1)-Related Epilepsy