TXNIP

Summary

TXNIP (thioredoxin interacting protein, HGNC:16952) is a protein-coding gene on chromosome 1q21.1, encoding Thioredoxin-interacting protein (Q9H3M7). May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability.

This gene encodes a thioredoxin-binding protein that is a member of the alpha arrestin protein family. Thioredoxin is a thiol-oxidoreductase that is a major regulator of cellular redox signaling which protects cells from oxidative stress. This protein inhibits the antioxidative function of thioredoxin resulting in the accumulation of reactive oxygen species and cellular stress. This protein also functions as a regulator of cellular metabolism and of endoplasmic reticulum (ER) stress. This protein may also function as a tumor suppressor. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 10628 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 66 total — 1 pathogenic
• MANE Select transcript: NM_006472

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16952
Approved symbol	TXNIP
Name	thioredoxin interacting protein
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	VDUP1, EST01027, HHCPA78, THIF, ARRDC6
Ensembl gene	ENSG00000265972
Ensembl biotype	protein_coding
OMIM	606599
Entrez	10628

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 retained_intron

ENST00000425134, ENST00000486597, ENST00000488537, ENST00000582401, ENST00000883752, ENST00000883753, ENST00000883754, ENST00000883755, ENST00000883756, ENST00000955254

RefSeq mRNA: 2 — MANE Select: NM_006472 NM_001313972, NM_006472

CCDS: CCDS72876, CCDS81368

Canonical transcript exons

ENST00000582401 — 8 exons

Exon	Start	End
ENSE00002687871	145994016	145994167
ENSE00002693030	145995404	145995476
ENSE00002703890	145992435	145993886
ENSE00002705473	145996017	145996579
ENSE00003713564	145994929	145995031
ENSE00003724826	145994281	145994437
ENSE00003730672	145995144	145995291
ENSE00003739755	145994544	145994800

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 304.7707 / max 6802.4829, expressed in 1760 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14189	303.0903	1760
14187	1.5130	590
14188	0.1675	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.86	gold quality
mucosa of stomach	UBERON:0001199	99.85	gold quality
cardia of stomach	UBERON:0001162	99.83	gold quality
pericardium	UBERON:0002407	99.79	gold quality
skin of hip	UBERON:0001554	99.77	gold quality
lower esophagus	UBERON:0013473	99.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.76	gold quality
renal medulla	UBERON:0000362	99.75	gold quality
deltoid	UBERON:0001476	99.75	gold quality
endocervix	UBERON:0000458	99.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.74	gold quality
gluteal muscle	UBERON:0002000	99.73	gold quality
nipple	UBERON:0002030	99.73	gold quality
calcaneal tendon	UBERON:0003701	99.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.72	gold quality
blood	UBERON:0000178	99.71	gold quality
mammary duct	UBERON:0001765	99.71	gold quality
upper leg skin	UBERON:0004262	99.70	gold quality
thoracic mammary gland	UBERON:0005200	99.70	gold quality
adult organism	UBERON:0007023	99.70	gold quality
colonic epithelium	UBERON:0000397	99.69	gold quality
caput epididymis	UBERON:0004358	99.69	gold quality
fundus of stomach	UBERON:0001160	99.68	gold quality
pylorus	UBERON:0001166	99.68	gold quality
right uterine tube	UBERON:0001302	99.68	gold quality
spleen	UBERON:0002106	99.68	gold quality
peritoneum	UBERON:0002358	99.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.68	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.68	gold quality
omental fat pad	UBERON:0010414	99.68	gold quality

Single-cell (SCXA)

Detected in 49 experiment(s), a significant marker in 29.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	5222.63
E-MTAB-9841	yes	3620.60
E-MTAB-8530	yes	2750.48
E-CURD-46	yes	2548.53
E-MTAB-8142	yes	2509.77
E-GEOD-89232	yes	2478.14
E-GEOD-124263	yes	2349.23
E-HCAD-1	yes	2259.74
E-MTAB-10432	yes	1874.21
E-MTAB-6701	yes	1444.13
E-MTAB-7052	yes	404.33
E-CURD-122	yes	65.55
E-MTAB-10553	yes	57.88
E-MTAB-8410	yes	52.24
E-GEOD-134144	yes	38.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, F2RL1, FOS, FOXO1, FOXO3, HDAC10, HDAC1, JUN, KLF6, MED23, MLX, MLXIP, MLXIPL, NFE2L2, PPARA, PPARG, RBMX, RXRA, SSRP1, TBPL2, TFE3, USF1

miRNA regulators (miRDB)

104 targeting TXNIP, 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-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 40)

• overexpression of mRNA sensitized HeLa cells to paraquat (PMID:12054598)
• association of induction with decreased mRNA levels in prostate cancer cells [thioredoxin-binding protein 2] (PMID:12189205)
• VDUP1 is a novel antitumor gene which forms a transcriptional repressor complex (PMID:12821938)
• VDUP1 could have a unique role in epidermis regulating the conversion of postmitotic cells to differentiating ones. (PMID:14632196)
• VDUP1 is upregulated by heat shock factor during stresses such as high density and serum deprivation cultures (PMID:14766217)
• reduced thioredoxin activity through interaction with Txnip is an important mechanism for vascular oxidative stress in diabetes mellitus (PMID:15128745)
• TXNIP gene does not ply a major role in familial combined hyperlipidemia, or related traits. (PMID:15136067)
• interaction of TBP-2 was specific to Rch1 among other importin alpha subfamilies (PMID:15234975)
• thioredoxin binding protein-2 and redox-sensitive signaling regulate human osteoclast differentiation (PMID:15537450)
• Data suggest that thioredoxin-interacting protein and thioredoxin are key components of biomechanical signal transduction and establish them as potentially novel regulators of tumor necrosis factor signaling and inflammation in endothelial cells. (PMID:15696199)
• thioredoxin-interacting protein (TXNIP)is a novel proapoptotic beta-cell gene elevated in insulin resistance/diabetes and up-regulated by glucose through a unique carbohydrate response element (PMID:15705778)
• findings indicate that txnip is a novel glucocorticoid-induced primary target gene involved in mediating glucocorticoid-induced apoptosis (PMID:16301999)
• By Northern blot, we confirm hypoxia-induced expression of insulin-like growth factor binding protein 3 (igfbp3), thioredoxin-interacting protein (txnip), neuritin (nrn1). (PMID:16723126)
• Txnip cysteines 63 and 247 are important for formation of a disulfide-linked complex with thioredoxin that inhibits thioredoxin’s reducing activity (PMID:16766796)
• identified two Txnip cysteines that are important for thioredoxin binding and showed that this interaction is consistent with a disulfide exchange reaction between oxidized Txnip and reduced thioredoxin (PMID:16766796)
• first report to implicate TXNIP in Type 2 diabetes; effect of TXNIP on triglycerides is influenced by plasma glucose concentration, suggesting biological relevance of TXNIP variations may be particularly relevant in recurrent episodes of hyperglycaemia (PMID:17381501)
• TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Data suggests that TXNIP might play a key role in defective glucose homeostasis preceding overt type 2 diabetes mellitus. (PMID:17472435)
• In response to glucose, increased level of TXNIP RNA is followed by increased level of protein that is associated with increasing levels of reactive oxygen species (ROS) and reduced thioredoxin activity in a metastatic breast cancer-derived cell line. (PMID:17555594)
• Enhanced VDUP1 gene expression by PPARgamma agonist induces apoptosis in human macrophages. (PMID:17579352)
• downregulation of TXNIP may be partly involved in the pathogenesis of ulcerative colitis, including inflammation and colitis-associated colon carcinogenesis. (PMID:17671698)
• Results suggest that high glucose induces Txnip through a TGF-beta1-independent pathway. (PMID:17675577)
• D-allose, a simple monosaccharide, may act to cause TXNIP induction and p27kip1 protein stabilization in tumor cells (PMID:18202760)
• TXNIP is directly repressed by FOXO1a, modulating the cellular response to oxidative stress and affecting life span (PMID:18301748)
• TXNIP is induced in response to hypoxia in a HIF-1alpha-dependent manner in pancreatic cancer cells, resulting in increased apoptosis and increased sensitivity to platinum anticancer therapy. (PMID:18376310)
• These studies suggest a key role for MondoA:Mlx complexes in the adaptive transcriptional response to changes in extracellular glucose concentration and peripheral glucose uptake. (PMID:18458340)
• These studies indicate that hnRNP G promotes the expression of Txnip and mediates its tumor-suppressive effect. (PMID:18541147)
• Results show that inhibition of TXNIP protects against glucotoxic beta-cell apoptosis and therefore may represent a novel therapeutic approach to halt diabetes progression. (PMID:18793170)
• The expressions of hypoxia inducible factor 1alpha, vascular endothelial growth factor-A, thioredoxin, and thioredoxin interacting protein were related to macrophage infiltration rather than neovascularization in carotid atherosclerotic plaques (PMID:18835792)
• stimulation of PPARalpha in human macrophages might reduce arterial inflammation through differential regulation of the Trx-1 and VDUP-1 gene expression (PMID:18848838)
• TXNIP is involved in the antitumor activity of CD437. (PMID:19018770)
• TXNIP is transcription induced in carcinoma cells in an increased glucose metabolism-dependent or -independent response, and a putative glucose regulatory system including ChREBP and ChoRE is needed for glucose-induced TXNIP gene in prostate carcinoma (PMID:19052253)
• Repression of TXNIP by insulin is probably an important compensatory mechanism protecting beta cells from oxidative damage and apoptosis in type 2 diabetes. (PMID:19214472)
• The transcription of the Txnip gene is induced by adenosine-containing molecules, of which an intact adenosine moiety is necessary and sufficient. (PMID:19246513)
• upregulation of Txnip and subsequent impairment of thioredoxin antioxidative system through p38 MAPK and FOXO1 may represent a novel mechanism for glucose-induced increase in intracellular ROS. (PMID:19254690)
• TXNIP expression contributes to mouse leukemia virus-induced murine leukemia as well as human acute myelocytic leukemia. (PMID:19327827)
• Txnip regulates cellular metabolism independent of its binding to thioredoxin and the arrestin domains are crucial structural elements in metabolic functions of alpha-arrestin proteins (PMID:19605364)
• Data suggest that thioredoxin binding protein 2 modulates lipid metabolism as well as natural killer T cell activity. (PMID:19619006)
• p21(WAF1) can induce thioredoxin secretion and angiogenesis in cancer cells, by direct transcriptional repression of the thioredoxin-binding protein 2 promoter (PMID:19773351)
• Data suggest that Txnip expression and promoter activity are mediated via divergent effects of KLF6 and PPAR-gamma transcriptional regulation. (PMID:19808645)
• Thioredoxin-interacting protein (Txnip) is a feedback regulator of S-nitrosylation. (PMID:19847012)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	txnipa	ENSDARG00000036107
danio_rerio	txnipb	ENSDARG00000070000
mus_musculus	Txnip	ENSMUSG00000038393
rattus_norvegicus	Txnip	ENSRNOG00000021201
caenorhabditis_elegans		WBGENE00008843
caenorhabditis_elegans		WBGENE00009852
caenorhabditis_elegans		WBGENE00011052
caenorhabditis_elegans		WBGENE00011053
caenorhabditis_elegans		WBGENE00011054
caenorhabditis_elegans		WBGENE00012464
caenorhabditis_elegans		WBGENE00013043
caenorhabditis_elegans		WBGENE00014161
caenorhabditis_elegans		WBGENE00018060
caenorhabditis_elegans		WBGENE00018061
caenorhabditis_elegans		WBGENE00020612

Paralogs (5): ARRDC2 (ENSG00000105643), ARRDC3 (ENSG00000113369), ARRDC4 (ENSG00000140450), ARRDC1 (ENSG00000197070), ARRDC5 (ENSG00000205784)

Protein

Protein identifiers

Thioredoxin-interacting protein — Q9H3M7 (reviewed: Q9H3M7)

Alternative names: Thioredoxin-binding protein 2, Vitamin D3 up-regulated protein 1

All UniProt accessions (1): Q9H3M7

UniProt curated annotations — full annotation on UniProt →

Function. May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).

Subunit / interactions. Homodimer; disulfide-linked. Interacts with TXN/thioredoxin through its redox-active site. Interacts with transcriptional repressors ZBTB16, ZBTB32 and HDAC1. Interacts with DDIT4.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Ubiquitinated; undergoes heterotypic ‘Lys-48’-/‘Lys-63’-branched polyubiquitination catalyzed by ITCH and UBR5 resulting in proteasomal degradation. Deubiquitinated by USP5, leading to TXNIP stabilization.

Induction. By 1,25-dihydroxyvitamin D-3 and TGFB1. Down-regulated in response to oxidative stress.

Similarity. Belongs to the arrestin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H3M7-1	1	yes
Q9H3M7-2	2

RefSeq proteins (2): NP_001300901, NP_006463* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011021	Arrestin-like_N	Domain
IPR011022	Arrestin-like_C	Domain
IPR014752	Arrestin-like_C_sf	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR050357	Arrestin_domain-protein	Family

Pfam: PF00339, PF02752

UniProt features (34 total): strand 26, chain 1, modified residue 1, disulfide bond 1, cross-link 1, helix 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5CQ2	X-RAY DIFFRACTION	1.4
4GEI	X-RAY DIFFRACTION	1.5
5DZD	X-RAY DIFFRACTION	1.57
4GFX	X-RAY DIFFRACTION	1.6
5DWS	X-RAY DIFFRACTION	1.65
5DF6	X-RAY DIFFRACTION	1.78
4ROJ	X-RAY DIFFRACTION	1.95
4LL1	X-RAY DIFFRACTION	2
4ROF	X-RAY DIFFRACTION	2.03
4LL4	X-RAY DIFFRACTION	2.7
4GEJ	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3M7-F1	78.85	0.49

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 (2): 361, 212

Disulfide bonds (1): 63

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-844456	The NLRP3 inflammasome
R-HSA-9617629	Regulation of FOXO transcriptional activity by acetylation
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-9707564	Cytoprotection by HMOX1

MSigDB gene sets: 613 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, FREAC2_01, BROWNE_HCMV_INFECTION_6HR_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELL_DIVISION, GOBP_INFLAMMATORY_RESPONSE, REACTOME_THE_NLRP3_INFLAMMASOME, JAEGER_METASTASIS_DN, REACTOME_INFLAMMASOMES

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), protein import into nucleus (GO:0006606), inflammatory response (GO:0006954), response to oxidative stress (GO:0006979), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), response to glucose (GO:0009749), protein transport (GO:0015031), keratinocyte differentiation (GO:0030216), response to estradiol (GO:0032355), response to progesterone (GO:0032570), regulation of cell population proliferation (GO:0042127), response to hydrogen peroxide (GO:0042542), positive regulation of apoptotic process (GO:0043065), platelet-derived growth factor receptor signaling pathway (GO:0048008), response to calcium ion (GO:0051592), negative regulation of cell division (GO:0051782), cellular response to tumor cell (GO:0071228), cellular response to oxidised low-density lipoprotein particle stimulus (GO:0140052)

GO Molecular Function (3): enzyme inhibitor activity (GO:0004857), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Inflammasomes	1
FOXO-mediated transcription	1
Cell recruitment (pro-inflammatory response)	1
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
defense response	1
response to stress	1
response to chemical	1
response to external stimulus	1
response to abiotic stimulus	1
response to hexose	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
epidermal cell differentiation	1
skin development	1
response to lipid	1
response to oxygen-containing compound	1
response to steroid hormone	1
response to ketone	1
cell population proliferation	1
regulation of cellular process	1
response to reactive oxygen species	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cell surface receptor protein tyrosine kinase signaling pathway	1
response to metal ion	1
negative regulation of cellular process	1
cell division	1
regulation of cell division	1
response to tumor cell	1
cellular response to biotic stimulus	1
cellular response to low-density lipoprotein particle stimulus	1
catalytic activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1

Protein interactions and networks

STRING

2468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNIP	TXN	P10599	999
TXNIP	NLRP3	Q96P20	995
TXNIP	TXN2	Q99757	994
TXNIP	DDIT4	Q9NX09	989
TXNIP	CASP1	P29466	862
TXNIP	MAP3K5	Q99683	840
TXNIP	IL1B	P01584	734
TXNIP	PRDX1	P35703	720
TXNIP	TP53	P04637	717
TXNIP	MLXIP	Q9HAP2	710
TXNIP	KPNA2	P52292	697
TXNIP	FKBP5	Q13451	697
TXNIP	ARRB1	P49407	650
TXNIP	UBA6	A0AVT1	633
TXNIP	UBA5	Q9GZZ9	624

IntAct

44 interactions, top by confidence:

A	B	Type	Score
TXNIP	TXN	psi-mi:“MI:0915”(physical association)	0.740
TXN	TXNIP	psi-mi:“MI:0915”(physical association)	0.740
ECD	TXNIP	psi-mi:“MI:0915”(physical association)	0.690
TXNIP	VAV2	psi-mi:“MI:0407”(direct interaction)	0.560
TXNIP	PER1	psi-mi:“MI:0914”(association)	0.530
TXNIP	HDAC2	psi-mi:“MI:0915”(physical association)	0.500
TXNIP	SRC	psi-mi:“MI:0407”(direct interaction)	0.440
TXNIP	SMARCA1	psi-mi:“MI:0915”(physical association)	0.400
TXNIP	PB2	psi-mi:“MI:0915”(physical association)	0.370
HSPB2	TXNIP	psi-mi:“MI:0915”(physical association)	0.370
TXNIP	FHL1	psi-mi:“MI:0915”(physical association)	0.370
SMURF2	TXNIP	psi-mi:“MI:0915”(physical association)	0.370
RGMA	BDP1	psi-mi:“MI:0914”(association)	0.350
IL12RB1	TUBB4A	psi-mi:“MI:0914”(association)	0.350
TXNIP	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100A4	VWA8	psi-mi:“MI:0914”(association)	0.350
WWP2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
CCT8L2	DVL2	psi-mi:“MI:0914”(association)	0.350
WWP1	TP73	psi-mi:“MI:0914”(association)	0.350
IL12RB1	HSPA5	psi-mi:“MI:0914”(association)	0.350
SCARA5	COLGALT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (330): DDIT4 (Reconstituted Complex), DDIT4 (Affinity Capture-Western), DDIT4 (Co-localization), TXN (Reconstituted Complex), TXNIP (Two-hybrid), TXNIP (Reconstituted Complex), TXNIP (Affinity Capture-Western), TXN (Affinity Capture-Western), TXNIP (Affinity Capture-Western), TXNIP (Reconstituted Complex), TXN (Two-hybrid), COPS5 (Affinity Capture-Western), CDKN1B (Affinity Capture-Western), TXNIP (Affinity Capture-Western), TXNIP (Affinity Capture-Western)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A2AWP8, A2RRH5, C9J798, O43374, O70277, O95294, P04629, P59926, Q0GA42, Q13368, Q14318, Q16512, Q29RM4, Q2HY40, Q2T9P3, Q2TBA3, Q5BIM1, Q5M7W1, Q5R5M3, Q5R811, Q5T7P8, Q5XIS9, Q62746, Q6PFQ7, Q6PFY8, Q7TNM2, Q7TP90, Q7Z4K8, Q8BG60, Q8BHT7, Q8BQC3, Q8C6N3, Q8CIW5, Q8IZ69, Q8NCT1, Q920N2, Q92546, Q925B4

Diamond homologs: A0A0B4J1F4, Q0VCA2, Q2HY40, Q5M7W1, Q5R5L7, Q5R811, Q6TXF1, Q7TP90, Q7TPQ9, Q8BG60, Q8NCT1, Q8TBH0, Q96B67, Q9D668, Q9H3M7, O45782, Q99KN1, Q02805

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
F2RL1	“down-regulates quantity by repression”	TXNIP	“transcriptional regulation”
MAPK1	“down-regulates quantity by destabilization”	TXNIP	phosphorylation
TXNIP	“up-regulates quantity by stabilization”	DDIT4	binding
AMPK	“down-regulates quantity by destabilization”	TXNIP	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
proteasome-mediated ubiquitin-dependent protein catabolic process	6	8.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	60
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1711161	GRCh37/hg19 1q21.1(chr1:145387023-145764679)x3	Pathogenic

SpliceAI

480 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145993885:G:GG	acceptor_gain	1.0000
1:145993886:A:AG	acceptor_gain	1.0000
1:145993886:AGG:A	acceptor_loss	1.0000
1:145993887:TA:T	acceptor_loss	1.0000
1:145993888:TTAG:T	acceptor_loss	1.0000
1:145993889:TTTA:T	acceptor_loss	1.0000
1:145994012:T:A	donor_loss	1.0000
1:145994013:G:GG	donor_gain	1.0000
1:145994013:GTGA:G	donor_loss	1.0000
1:145994016:GAG:G	donor_gain	1.0000
1:145994166:G:GT	acceptor_gain	1.0000
1:145994166:GC:G	acceptor_gain	1.0000
1:145994166:GCT:G	acceptor_gain	1.0000
1:145994166:GCTC:G	acceptor_gain	1.0000
1:145994166:GCTCC:G	acceptor_gain	1.0000
1:145994167:A:AG	acceptor_gain	1.0000
1:145994278:G:GA	donor_loss	1.0000
1:145994282:GAAG:G	donor_gain	1.0000
1:145994318:A:G	donor_gain	1.0000
1:145994436:G:GG	acceptor_gain	1.0000
1:145994436:GAT:G	acceptor_gain	1.0000
1:145994436:GATCT:G	acceptor_gain	1.0000
1:145994437:A:AG	acceptor_gain	1.0000
1:145994437:A:AT	acceptor_loss	1.0000
1:145994438:TA:T	acceptor_loss	1.0000
1:145994558:T:G	donor_gain	1.0000
1:145994925:T:A	donor_loss	1.0000
1:145994926:GT:G	donor_loss	1.0000
1:145994928:AGG:A	donor_loss	1.0000
1:145994929:AAG:A	donor_gain	1.0000

AlphaMissense

2566 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145994627:A:G	W250R	1.000
1:145994627:A:T	W250R	1.000
1:145994737:G:T	A213D	1.000
1:145994743:G:T	P211H	1.000
1:145994766:A:C	N203K	1.000
1:145994766:A:T	N203K	1.000
1:145994958:G:T	A182D	1.000
1:145994394:A:G	L292P	0.999
1:145994548:A:G	L276S	0.999
1:145994625:C:A	W250C	0.999
1:145994625:C:G	W250C	0.999
1:145994714:A:C	Y221D	0.999
1:145994735:C:G	A214P	0.999
1:145994738:C:G	A213P	0.999
1:145994743:G:C	P211R	0.999
1:145994755:C:G	R207P	0.999
1:145994768:T:C	N203D	0.999
1:145994768:T:G	N203H	0.999
1:145994779:G:T	A199D	0.999
1:145994780:C:G	A199P	0.999
1:145994964:A:T	V180D	0.999
1:145994976:C:T	G176E	0.999
1:145995187:A:G	F143S	0.999
1:145995259:C:T	G119E	0.999
1:145995260:C:A	G119W	0.999
1:145995424:G:C	F101L	0.999
1:145995424:G:T	F101L	0.999
1:145995426:A:G	F101L	0.999
1:145996118:C:T	G50E	0.999
1:145996124:G:T	A48D	0.999

dbSNP variants (sampled 300 via entrez): RS1000189985 (1:145994787 G>A), RS1000219417 (1:145995017 A>G), RS1000527363 (1:145993600 G>A,C), RS1001896968 (1:145998573 G>A), RS1001967957 (1:145993267 A>G), RS1002032286 (1:145994546 G>A,C), RS1002338477 (1:145993025 G>A), RS1003574720 (1:145997010 A>C,G), RS1003608121 (1:145991955 G>A), RS1004045693 (1:145992131 C>T), RS1005031302 (1:145994180 A>G), RS1005264117 (1:145998198 C>A,G), RS1005366474 (1:145992929 G>A), RS1005396171 (1:145993242 C>A,T), RS1006705950 (1:145997313 T>C)

Disease associations

OMIM: gene MIM:606599 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, affects expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
perfluorooctanoic acid	decreases expression, increases expression	5
(+)-JQ1 compound	decreases expression, increases expression	5
Silicon Dioxide	affects expression, increases expression, decreases expression	5
Cadmium Chloride	decreases reaction, increases abundance, increases expression, decreases expression	5
Cisplatin	affects cotreatment, decreases expression, decreases reaction, increases expression, affects expression	4
Estradiol	increases cleavage, affects cotreatment, decreases expression, decreases reaction, increases expression	4
Glucose	increases expression, affects cotreatment, decreases expression, increases reaction, increases response to substance (+1 more)	4
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Cyclosporine	affects expression, decreases expression, increases expression, decreases reaction	4
bisphenol A	decreases expression, increases expression	3
enniatins	affects cotreatment, increases expression	3
Arsenic Trioxide	decreases expression	3
Cadmium	decreases expression, decreases reaction, increases abundance, increases expression	3
Fluorouracil	increases expression, increases reaction, affects reaction, decreases expression, affects response to substance (+1 more)	3
Plant Extracts	affects cotreatment, increases expression	3
Rotenone	decreases expression	3
Aflatoxin B1	increases expression, affects expression, affects cotreatment	3
beauvericin	affects cotreatment, increases expression, decreases expression	2
methylmercuric chloride	decreases expression	2
lead acetate	decreases expression, affects cotreatment	2
perfluorodecanoic acid	decreases expression, increases expression	2
perfluorooctane sulfonic acid	affects expression, increases expression	2
pentabromodiphenyl ether	decreases expression	2
perfluoro-n-nonanoic acid	increases expression	2
entinostat	decreases expression, affects cotreatment	2
bisphenol S	decreases expression	2
Resveratrol	decreases expression, increases expression	2

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7DT	Abcam A-549 TXNIP KO	Cancer cell line	Male
CVCL_C7EH	Abcam HCT 116 TXNIP KO	Cancer cell line	Male
CVCL_C7EV	Abcam THP-1 TXNIP KO	Cancer cell line	Male
CVCL_E0SG	Ubigene HeLa TXNIP KO	Cancer cell line	Female
CVCL_TV29	HAP1 TXNIP (-) 1	Cancer cell line	Male
CVCL_XU83	HAP1 TXNIP (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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