TXNL4B

Summary

TXNL4B (thioredoxin like 4B, HGNC:26041) is a protein-coding gene on chromosome 16q22.2, encoding Thioredoxin-like protein 4B (Q9NX01). Essential role in pre-mRNA splicing. It is a selective cancer dependency (DepMap: 86.8% of cell lines).

Predicted to be involved in mRNA splicing, via spliceosome. Located in cytosol and nucleoplasm.

Source: NCBI Gene 54957 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 28 total
• Cancer dependency (DepMap): dependent in 86.8% of screened cell lines
• MANE Select transcript: NM_017853

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26041
Approved symbol	TXNL4B
Name	thioredoxin like 4B
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20511, DLP, Dim2
Ensembl gene	ENSG00000140830
Ensembl biotype	protein_coding
OMIM	617722
Entrez	54957

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 nonsense_mediated_decay

ENST00000268483, ENST00000423037, ENST00000426362, ENST00000565171, ENST00000569767, ENST00000851364, ENST00000851365, ENST00000851366, ENST00000851367, ENST00000924900, ENST00000924901

RefSeq mRNA: 5 — MANE Select: NM_017853 NM_001142317, NM_001142318, NM_001324354, NM_001324355, NM_017853

CCDS: CCDS10906

Canonical transcript exons

ENST00000268483 — 4 exons

Exon	Start	End
ENSE00001032941	72093367	72093620
ENSE00001833110	72084857	72086802
ENSE00004472061	72090618	72090786
ENSE00004475000	72088987	72089138

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 86.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4430 / max 179.4347, expressed in 1787 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158058	6.3103	1759
158057	1.3200	873
158060	0.8128	218

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	86.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.70	gold quality
monocyte	CL:0000576	85.27	gold quality
mononuclear cell	CL:0000842	85.17	gold quality
leukocyte	CL:0000738	84.91	gold quality
cranial nerve II	UBERON:0000941	84.34	gold quality
pancreatic ductal cell	CL:0002079	84.24	silver quality
globus pallidus	UBERON:0001875	84.04	gold quality
left ovary	UBERON:0002119	83.78	gold quality
right lobe of liver	UBERON:0001114	83.66	gold quality
endothelial cell	CL:0000115	83.41	gold quality
secondary oocyte	CL:0000655	83.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.85	gold quality
tibial nerve	UBERON:0001323	82.69	gold quality
right ovary	UBERON:0002118	82.63	gold quality
right testis	UBERON:0004534	82.52	gold quality
oocyte	CL:0000023	82.50	gold quality
granulocyte	CL:0000094	82.47	gold quality
cortical plate	UBERON:0005343	82.47	gold quality
left testis	UBERON:0004533	82.29	gold quality
ovary	UBERON:0000992	82.22	gold quality
ventricular zone	UBERON:0003053	82.07	gold quality
testis	UBERON:0000473	81.90	gold quality
blood	UBERON:0000178	81.61	gold quality
tendon of biceps brachii	UBERON:0008188	81.58	gold quality
body of pancreas	UBERON:0001150	81.11	gold quality
gastrocnemius	UBERON:0001388	80.56	gold quality
ganglionic eminence	UBERON:0004023	80.40	gold quality
omental fat pad	UBERON:0010414	80.38	gold quality
peritoneum	UBERON:0002358	80.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting TXNL4B, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6733-5P	99.74	67.94	2759
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 86.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• DLP is implicated in not only cell cycle progression but also in a more specific molecular process such as pre-mRNA splicing (PMID:15161931)
• crystal structure; in contrast to hDim1, hDim2 forms stable homodimers (PMID:16142897)
• The human gene coding for the spliceosomal protein thioredoxin-like 4B (TXNL4B) was overexpressed in Escherichia coli and the encoded protein was purified and crystallized. (PMID:16511018)
• A crystal structure of TXNL4B was determined at 1.33 A resolution and refined to an Rwork of 0.13 and an Rfree of 0.18 with one native dimer in the asymmetric unit. (PMID:23519793)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	txnl4b	ENSDARG00000058962
mus_musculus	Txnl4b	ENSMUSG00000031723
rattus_norvegicus	Txnl4b	ENSRNOG00000021379

Paralogs (1): TXNL4A (ENSG00000141759)

Protein

Protein identifiers

Thioredoxin-like protein 4B — Q9NX01 (reviewed: Q9NX01)

Alternative names: Dim1-like protein

All UniProt accessions (3): Q9NX01, H3BQ09, H3BUL8

UniProt curated annotations — full annotation on UniProt →

Function. Essential role in pre-mRNA splicing. Required in cell cycle progression for S/G(2) transition.

Subunit / interactions. Homodimer. Interacts with the U5-102 kDa protein subunit of the spliceosome.

Subcellular location. Nucleus.

Similarity. Belongs to the DIM1 family.

RefSeq proteins (5): NP_001135789, NP_001135790, NP_001311283, NP_001311284, NP_060323* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004123	Dim1	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF02966

UniProt features (16 total): strand 8, helix 5, turn 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4IN0	X-RAY DIFFRACTION	1.33
3GIX	X-RAY DIFFRACTION	1.33
1XBS	X-RAY DIFFRACTION	2.5
8Y6O	ELECTRON MICROSCOPY	3.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NX01-F1	92.24	0.88

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): chr16q22, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CHX10_01, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_SPLICEOSOMAL_SNRNP_ASSEMBLY, GOCC_PRECATALYTIC_SPLICEOSOME, TAATTA_CHX10_01, GOCC_SPLICEOSOMAL_TRI_SNRNP_COMPLEX, GOCC_U5_SNRNP, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U5 snRNP (GO:0005682), cytosol (GO:0005829), U4/U6 x U5 tri-snRNP complex (GO:0046540), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
binding	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
cytoplasm	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNL4B	NOB1	Q9ULX3	806
TXNL4B	BYSL	Q13895	700
TXNL4B	LTV1	Q96GA3	678
TXNL4B	TSR1	Q2NL82	655
TXNL4B	RIOK1	Q9BRS2	594
TXNL4B	RIOK2	Q9BVS4	573
TXNL4B	RRP12	Q5JTH9	506
TXNL4B	XPO1	O14980	501
TXNL4B	PNO1	Q9NRX1	480
TXNL4B	ZNF821	O75541	465
TXNL4B	IL6	P05231	409
TXNL4B	TRDMT1	O14717	400
TXNL4B	PMFBP1	Q8TBY8	385
TXNL4B	SEC22A	Q96IW7	375
TXNL4B	PRPF6	O94906	373

IntAct

58 interactions, top by confidence:

A	B	Type	Score
CENATAC	TXNL4B	psi-mi:“MI:0915”(physical association)	0.770
PRPF3	PRPF4	psi-mi:“MI:0914”(association)	0.730
TXNL4B	TCF4	psi-mi:“MI:0915”(physical association)	0.670
TCF4	TXNL4B	psi-mi:“MI:0915”(physical association)	0.670
EMC4	EMC8	psi-mi:“MI:0914”(association)	0.640
TXNL4B	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
BHLHE40	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
REL	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
PNMA5	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
TXNL4B	REL	psi-mi:“MI:0915”(physical association)	0.560
TXNL4B	PNMA5	psi-mi:“MI:0915”(physical association)	0.560
PLEKHF2	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
TXNL4B	SF1	psi-mi:“MI:0915”(physical association)	0.560
PICK1	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
MEOX1	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
TXNL4B	SPG21	psi-mi:“MI:0915”(physical association)	0.560
TXNL4B	AIPL1	psi-mi:“MI:0915”(physical association)	0.560
SF1	TXNL4B	psi-mi:“MI:0915”(physical association)	0.560
TXNL4B	ALKBH4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (45): TXNL4B (Affinity Capture-MS), TXNL4B (Two-hybrid), TXNL4B (Two-hybrid), TXNL4B (Two-hybrid), PLEKHF2 (Two-hybrid), PNMA5 (Two-hybrid), TXNL4B (Affinity Capture-MS), TXNL4B (Affinity Capture-MS), TXNL4B (Affinity Capture-RNA), PRPF6 (Reconstituted Complex), TXNL4B (Affinity Capture-Western), TXNL4B (Two-hybrid), TXNL4B (Two-hybrid), TXNL4B (Two-hybrid), TXNL4B (Two-hybrid)

ESM2 similar proteins: A6QNX3, B2GV77, P09851, P20936, P50904, P61970, P61971, P61972, Q1JP79, Q29425, Q2KI42, Q2KIW0, Q2TBL9, Q32KP9, Q3UNA4, Q4R4K5, Q4R5H6, Q5E9J4, Q5F415, Q5FVJ7, Q5R8G4, Q5R8I6, Q5RB36, Q5RES2, Q5RKN4, Q5ZLH0, Q6PC62, Q8BG32, Q8BUH1, Q8IUI8, Q8K0F1, Q8MJJ1, Q92747, Q93034, Q99PD4, Q9CQC8, Q9CZQ9, Q9D5V5, Q9DAI2, Q9ES56

Diamond homologs: P83876, P83877, P87215, Q06819, Q553S5, Q6FMI2, Q75BD8, Q8BUH1, Q9FE62, Q9NX01

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
mRNA Splicing - Major Pathway	5	18.2×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	6	19.6×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

959 predictions. Top by Δscore:

Variant	Effect	Δscore
16:72088980:CACT:C	donor_loss	1.0000
16:72088982:CTTA:C	donor_loss	1.0000
16:72088983:TTAC:T	donor_loss	1.0000
16:72088985:A:AC	donor_gain	1.0000
16:72088985:AC:A	donor_gain	1.0000
16:72088986:C:CC	donor_gain	1.0000
16:72088986:C:G	donor_loss	1.0000
16:72088986:CC:C	donor_gain	1.0000
16:72089134:GAAAG:G	acceptor_gain	1.0000
16:72089135:AAAG:A	acceptor_gain	1.0000
16:72089136:AAG:A	acceptor_gain	1.0000
16:72089137:AG:A	acceptor_gain	1.0000
16:72089139:C:CC	acceptor_gain	1.0000
16:72089139:C:CG	acceptor_loss	1.0000
16:72090616:A:AC	donor_gain	1.0000
16:72090617:C:CC	donor_gain	1.0000
16:72090617:CA:C	donor_gain	1.0000
16:72090617:CAAT:C	donor_gain	1.0000
16:72090712:T:TA	donor_gain	1.0000
16:72090784:CTC:C	acceptor_gain	1.0000
16:72089145:A:C	acceptor_gain	0.9900
16:72090611:CACT:C	donor_loss	0.9900
16:72090612:ACTT:A	donor_loss	0.9900
16:72090613:CTT:C	donor_loss	0.9900
16:72090614:TTA:T	donor_loss	0.9900
16:72090615:TAC:T	donor_loss	0.9900
16:72090616:ACA:A	donor_loss	0.9900
16:72090617:C:G	donor_loss	0.9900
16:72090617:CAATA:C	donor_gain	0.9900
16:72090785:TC:T	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000186493 (16:72091770 AGT>A), RS1000251444 (16:72086374 G>A), RS1000379312 (16:72091909 C>T), RS1000519009 (16:72092906 G>A), RS1000570044 (16:72092768 G>T), RS1000986196 (16:72093062 C>A), RS1000999539 (16:72087698 C>T), RS1001249964 (16:72092810 A>G,T), RS1001642359 (16:72087325 CTTGTGTGT>C), RS1001666423 (16:72085416 A>G), RS1001913233 (16:72090265 G>C), RS1001936437 (16:72087155 A>G), RS1002010864 (16:72095803 C>T), RS1002041898 (16:72096058 C>T), RS1002375982 (16:72088350 C>T)

Disease associations

OMIM: gene MIM:617722 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST005195_143	Coronary artery disease	3.000000e-11
GCST005196_18	Coronary artery disease	3.000000e-11
GCST007441_8	Total cholesterol levels	2.000000e-09
GCST007442_6	Low density lipoprotein cholesterol levels	1.000000e-08
GCST007931_67	Medication use (HMG CoA reductase inhibitors)	2.000000e-08
GCST010173_31	Triglyceride levels	4.000000e-16
GCST010204_4	Low density lipoprotein cholesterol levels	5.000000e-105
GCST010243_229	Apolipoprotein B levels	1.000000e-76
GCST010244_241	Triglyceride levels	1.000000e-27
GCST010245_223	LDL cholesterol levels	2.000000e-73
GCST012232_26	Lipoprotein (a) levels	2.000000e-15
GCST90002383_247	Hematocrit	1.000000e-18
GCST90002384_365	Hemoglobin	2.000000e-19
GCST90002403_681	Red blood cell count	2.000000e-24

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004530	triglyceride measurement
EFO:0004615	apolipoprotein B measurement
EFO:0006925	lipoprotein A measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

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
Valproic Acid	affects cotreatment, increases expression, affects expression	4
Rotenone	decreases expression	3
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	increases expression	1
lasiocarpine	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	decreases expression, increases expression	1
cypermethrin	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression, increases reaction	1
picoxystrobin	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1

Clinical trials (associated diseases)

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