THOC3

Summary

THOC3 (THO complex subunit 3, HGNC:19072) is a protein-coding gene on chromosome 5q35.2, encoding THO complex subunit 3 (Q96J01). Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

This gene encodes a component of the nuclear THO transcription elongation complex, which is part of the larger transcription export (TREX) complex that couples messenger RNA processing and export. In humans, the transcription export complex is recruited to the 5’-end of messenger RNAs in a splicing- and cap-dependent manner. Studies of a related complex in mouse suggest that the metazoan transcription export complex is involved in cell differentiation and development. A pseudogene of this gene has been defined on chromosome 5.

Source: NCBI Gene 84321 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_032361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19072
Approved symbol	THOC3
Name	THO complex subunit 3
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	TEX1, MGC5469
Ensembl gene	ENSG00000051596
Ensembl biotype	protein_coding
OMIM	606929
Entrez	84321

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000265097, ENST00000432305, ENST00000505969, ENST00000510300, ENST00000511062, ENST00000513006, ENST00000513118, ENST00000513482, ENST00000514250, ENST00000514861, ENST00000515016, ENST00000628318, ENST00000909314, ENST00000909315, ENST00000928777, ENST00000928778, ENST00000928779, ENST00000928780, ENST00000928781, ENST00000960460

RefSeq mRNA: 2 — MANE Select: NM_032361 NM_001376902, NM_032361

CCDS: CCDS4397, CCDS93829

Canonical transcript exons

ENST00000265097 — 6 exons

Exon	Start	End
ENSE00002467360	175959531	175960132
ENSE00003459846	175961051	175961151
ENSE00003557520	175964951	175965155
ENSE00003618727	175961273	175961434
ENSE00003681177	175967111	175967267
ENSE00003899832	175967942	175968315

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 96.73.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.73	gold quality
esophagus mucosa	UBERON:0002469	96.57	gold quality
right testis	UBERON:0004534	96.21	gold quality
left testis	UBERON:0004533	95.46	gold quality
testis	UBERON:0000473	94.98	gold quality
embryo	UBERON:0000922	94.01	gold quality
ganglionic eminence	UBERON:0004023	94.01	gold quality
tonsil	UBERON:0002372	93.68	gold quality
lymph node	UBERON:0000029	93.25	gold quality
prefrontal cortex	UBERON:0000451	92.82	gold quality
cerebellum	UBERON:0002037	92.52	gold quality
cerebellar cortex	UBERON:0002129	92.47	gold quality
cerebellar hemisphere	UBERON:0002245	92.45	gold quality
islet of Langerhans	UBERON:0000006	92.17	gold quality
rectum	UBERON:0001052	91.88	gold quality
ventricular zone	UBERON:0003053	91.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.70	gold quality
vagina	UBERON:0000996	91.62	gold quality
cortical plate	UBERON:0005343	91.60	gold quality
mucosa of transverse colon	UBERON:0004991	91.52	gold quality
superior frontal gyrus	UBERON:0002661	91.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.93	gold quality
frontal cortex	UBERON:0001870	90.60	gold quality
frontal lobe	UBERON:0016525	90.60	gold quality
bone marrow	UBERON:0002371	90.51	gold quality
stromal cell of endometrium	CL:0002255	90.48	gold quality
esophagus	UBERON:0001043	90.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.88	gold quality
placenta	UBERON:0001987	89.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.51

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• recruitment of the human TREX complex to spliced mRNA is not directly coupled to transcription, but is instead coupled to transcription indirectly through splicing (PMID:15998806)
• THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification. (PMID:37500615)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	thoc3	ENSDARG00000056517
mus_musculus	Thoc3	ENSMUSG00000025872
rattus_norvegicus	Thoc3	ENSRNOG00000000104
drosophila_melanogaster	tex	FBGN0037569

Protein

Protein identifiers

THO complex subunit 3 — Q96J01 (reviewed: Q96J01)

Alternative names: TEX1 homolog, hTREX45

All UniProt accessions (8): D6REC9, D6RGZ2, Q96J01, H0Y9T1, H0YA11, H0YAG7, H0YAJ0, H7C0C5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. Required for efficient export of polyadenylated RNA and spliced mRNA. The THOC1-THOC2-THOC3 core complex alone is sufficient to bind export factor NXF1-NXT1 and promote ATPase activity of DDX39B. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5’ end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. (Microbial infection) The TREX complex is essential for the export of Kaposi’s sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.

Subunit / interactions. Component of the THO subcomplex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7. The THO subcomplex interacts with DDX39B to form the THO-DDX39B complex which multimerizes into a 28-subunit tetrameric assembly. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; in the complex interacts with THOC2. TREX seems to have a dynamic structure involving ATP-dependent remodeling.

Subcellular location. Nucleus. Nucleus speckle.

Similarity. Belongs to the THOC3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96J01-1	1	yes
Q96J01-2	2

RefSeq proteins (2): NP_001363831, NP_115737* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR040132	Tex1/THOC3	Family

Pfam: PF25174

UniProt features (45 total): strand 27, repeat 6, turn 5, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, helix 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7APK	ELECTRON MICROSCOPY	3.3
7ZNL	ELECTRON MICROSCOPY	3.45
7ZNK	ELECTRON MICROSCOPY	3.9
8R7L	ELECTRON MICROSCOPY	4.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96J01-F1	91.07	0.87

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 100 (showing top): MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NUCLEAR_TRANSPORT, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_RNA_SPLICING, GOBP_NUCLEAR_EXPORT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_RNA_LOCALIZATION, GRADE_COLON_AND_RECTAL_CANCER_UP, REACTOME_METABOLISM_OF_RNA, GOCC_TRANSCRIPTION_EXPORT_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_CHROMOSOMAL_REGION, GOCC_NUCLEAR_BODY

GO Biological Process (4): mRNA processing (GO:0006397), mRNA export from nucleus (GO:0006406), RNA splicing (GO:0008380), mRNA transport (GO:0051028)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): transcription export complex (GO:0000346), THO complex part of transcription export complex (GO:0000445), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	2
Transport of Mature Transcript to Cytoplasm	1
RNA Polymerase II Transcription	1
Metabolism of RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
cellular anatomical structure	2
mRNA metabolic process	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
RNA transport	1
nucleic acid binding	1
binding	1
nuclear protein-containing complex	1
transcription export complex	1
THO complex	1
nuclear lumen	1
nuclear ribonucleoprotein granule	1
chromosomal region	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THOC3	THOC2	Q8NI27	999
THOC3	THOC1	Q96FV9	999
THOC3	DDX39B	Q13838	998
THOC3	THOC5	Q13769	997
THOC3	THOC7	Q6I9Y2	997
THOC3	THOC6	Q86W42	997
THOC3	CYLD	Q9NQC7	989
THOC3	GLI2	P10070	986
THOC3	ALYREF	Q86V81	963
THOC3	SARNP	P82979	846
THOC3	NXF1	Q9UBU9	750
THOC3	TEX2	Q8IWB9	670
THOC3	FYTTD1	Q96QD9	665
THOC3	CHTOP	Q9Y3Y2	631
THOC3	NCBP3	Q53F19	628

IntAct

66 interactions, top by confidence:

A	B	Type	Score
DDX39B	THOC5	psi-mi:“MI:0915”(physical association)	0.800
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
THOC1	EIF4A3	psi-mi:“MI:0914”(association)	0.660
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
THOC3	CLUH	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
	EIF4A3	psi-mi:“MI:0915”(physical association)	0.490
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CHTOP	SAP18	psi-mi:“MI:0915”(physical association)	0.400
NUDCD2	THOC3	psi-mi:“MI:0915”(physical association)	0.400
THOC3	DLG4	psi-mi:“MI:0915”(physical association)	0.370
THOC3	MLKL	psi-mi:“MI:0915”(physical association)	0.370
TK1	THOC3	psi-mi:“MI:0915”(physical association)	0.370
THOC2		psi-mi:“MI:0914”(association)	0.350
THOC1	TARS3	psi-mi:“MI:0914”(association)	0.350
THOC5	MYO1G	psi-mi:“MI:0914”(association)	0.350
THOC7	ALYREF	psi-mi:“MI:0914”(association)	0.350
BCLAF1	PABPN1	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
	ANKRD28	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350

BioGRID (212): PAK2 (Co-fractionation), THOC1 (Co-fractionation), THOC2 (Co-fractionation), THOC3 (Co-fractionation), THOC3 (Co-fractionation), THOC6 (Co-fractionation), THOC3 (Affinity Capture-MS), THOC3 (Affinity Capture-MS), THOC3 (Affinity Capture-MS), THOC3 (Affinity Capture-MS), THOC3 (Affinity Capture-MS), THOC3 (Affinity Capture-MS), THOC1 (Affinity Capture-MS), THOC7 (Affinity Capture-MS), THOC5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EXB5, A4QNE6, A8WGF4, C1BK83, O35142, O43684, O55029, P35605, P35606, Q17QU5, Q1JP79, Q1JQB2, Q29RH4, Q29RZ9, Q3UGF1, Q4FZW5, Q4R4I8, Q561Y0, Q5I0B4, Q5M7F6, Q5MNZ6, Q5R664, Q5RB58, Q5U4Y8, Q5VQ78, Q6GNF1, Q6NWV3, Q6PA72, Q6TGU2, Q803V5, Q8AVT9, Q8BGF3, Q8IWZ6, Q8K2G4, Q8L828, Q8NEZ3, Q8VE80, Q92747, Q96J01, Q96MX6

Diamond homologs: A0JMQ0, A1CQI9, A1D3F5, A2QPZ4, A3LXF0, A4H6F7, A4HUV2, A4IHS2, A4R0Q1, A4RDD7, A5DBG1, A5DWF4, A6QX61, A6RRD4, A6RT32, A6RUL1, A6ZMA9, A7EF03, A8ID74, A8NWR2, A8PWB6, A8QD31, A8XYW9, A9UZS7, B0WC36, B0XQ42, B2AY28, B2VR76, B3MHX6, B3NLK7, B4GIU9, B4HN85, B4J9K1, B4KQU8, B4LKS9, B4MYI5, B4P528, B8M7Q5, B8NGT5, B9WD30

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
THOC3	“form complex”	“TREX complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Transport of Mature Transcript to Cytoplasm	7	56.7×	2e-09
mRNA 3’-end processing	13	54.5×	1e-17
Transport of Mature mRNA derived from an Intron-Containing Transcript	12	38.9×	2e-14
RNA Polymerase II Transcription Termination	8	37.4×	2e-09
Processing of Capped Intron-Containing Pre-mRNA	9	15.7×	2e-07
mRNA Splicing	5	11.7×	1e-03
mRNA Splicing - Major Pathway	9	10.5×	7e-06
Metabolism of RNA	9	8.0×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	10	47.7×	4e-12
RNA splicing	11	15.7×	3e-08
mRNA processing	11	14.0×	6e-08
mRNA splicing, via spliceosome	6	8.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1214 predictions. Top by Δscore:

Variant	Effect	Δscore
5:175960132:CCT:C	acceptor_loss	1.0000
5:175960133:C:A	acceptor_loss	1.0000
5:175960134:T:A	acceptor_loss	1.0000
5:175961147:CCAGC:C	acceptor_gain	1.0000
5:175961148:CAGC:C	acceptor_gain	1.0000
5:175961148:CAGCC:C	acceptor_gain	1.0000
5:175961149:AGC:A	acceptor_gain	1.0000
5:175961150:GC:G	acceptor_gain	1.0000
5:175961150:GCC:G	acceptor_loss	1.0000
5:175961151:CCTA:C	acceptor_gain	1.0000
5:175961152:C:CC	acceptor_gain	1.0000
5:175961152:C:CG	acceptor_loss	1.0000
5:175961152:C:T	acceptor_gain	1.0000
5:175961153:T:C	acceptor_loss	1.0000
5:175961154:A:AC	acceptor_gain	1.0000
5:175961154:A:C	acceptor_gain	1.0000
5:175961157:A:AC	acceptor_gain	1.0000
5:175961157:A:C	acceptor_gain	1.0000
5:175961160:CAGAG:C	acceptor_gain	1.0000
5:175961161:A:T	acceptor_gain	1.0000
5:175961164:G:C	acceptor_gain	1.0000
5:175961164:G:GC	acceptor_gain	1.0000
5:175961169:C:CT	acceptor_gain	1.0000
5:175961269:TTACC:T	donor_loss	1.0000
5:175961270:TACCT:T	donor_loss	1.0000
5:175961271:A:AC	donor_gain	1.0000
5:175961271:AC:A	donor_gain	1.0000
5:175961272:C:CC	donor_gain	1.0000
5:175961272:CC:C	donor_gain	1.0000
5:175961338:T:TA	donor_gain	1.0000

AlphaMissense

2350 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:175960080:C:A	W315C	1.000
5:175960080:C:G	W315C	1.000
5:175960082:A:G	W315R	1.000
5:175960082:A:T	W315R	1.000
5:175960085:C:G	A314P	1.000
5:175961084:C:G	D287H	1.000
5:175961090:A:G	S285P	1.000
5:175961092:G:T	A284E	1.000
5:175961098:G:T	A282E	1.000
5:175961121:G:C	F274L	1.000
5:175961121:G:T	F274L	1.000
5:175961122:A:G	F274S	1.000
5:175961123:A:G	F274L	1.000
5:175961133:T:A	R270S	1.000
5:175961133:T:G	R270S	1.000
5:175961311:C:A	W251C	1.000
5:175961311:C:G	W251C	1.000
5:175961312:C:G	W251S	1.000
5:175961313:A:G	W251R	1.000
5:175961313:A:T	W251R	1.000
5:175961315:A:G	L250P	1.000
5:175961321:A:T	V248D	1.000
5:175961328:C:G	A246P	1.000
5:175961330:T:A	D245V	1.000
5:175961331:C:G	D245H	1.000
5:175961335:A:C	S243R	1.000
5:175961335:A:T	S243R	1.000
5:175961336:C:A	S243I	1.000
5:175961337:T:G	S243R	1.000
5:175961339:C:T	G242E	1.000

dbSNP variants (sampled 300 via entrez): RS1002031700 (5:175968941 A>G), RS1003702495 (5:175962218 T>C), RS1003744992 (5:175962835 A>G), RS1007937640 (5:175960591 G>A), RS1008021935 (5:175966375 C>G), RS1008340533 (5:175959567 A>G,T), RS1010776544 (5:175967011 T>C), RS1011213376 (5:175968531 T>G), RS1012864460 (5:175960772 G>A), RS1012927901 (5:175962682 G>A), RS1015042995 (5:175962240 C>T), RS1015064385 (5:175962961 T>G), RS1018230572 (5:175963868 T>A,C), RS1019257804 (5:175960707 A>G), RS1019329616 (5:175964826 T>C)

Disease associations

OMIM: gene MIM:606929 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007576_353	Chronotype	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases expression, decreases expression	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2II	Abcam HeLa THOC3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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