DUOX2

Summary

DUOX2 (dual oxidase 2, HGNC:13273) is a protein-coding gene on chromosome 15q21.1, encoding Dual oxidase 2 (Q9NRD8). Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO.

The protein encoded by this gene is a glycoprotein and a member of the NADPH oxidase family. The synthesis of thyroid hormone is catalyzed by a protein complex located at the apical membrane of thyroid follicular cells. This complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes this encoded protein and DUOX1. This protein is known as dual oxidase because it has both a peroxidase homology domain and a gp91phox domain.

Source: NCBI Gene 50506 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thyroid dyshormonogenesis 6 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 2,360 total — 120 pathogenic, 83 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes
• MANE Select transcript: NM_001363711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13273
Approved symbol	DUOX2
Name	dual oxidase 2
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	P138-TOX, P138(TOX), THOX2, LNOX2
Ensembl gene	ENSG00000140279
Ensembl biotype	protein_coding
OMIM	606759
Entrez	50506

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 retained_intron, 2 protein_coding

ENST00000389039, ENST00000558383, ENST00000558416, ENST00000560797, ENST00000603300

RefSeq mRNA: 2 — MANE Select: NM_001363711 NM_001363711, NM_014080

CCDS: CCDS10117, CCDS86454

Canonical transcript exons

ENST00000389039 — 34 exons

Exon	Start	End
ENSE00000942162	45101793	45101989
ENSE00000942164	45100755	45100838
ENSE00000942166	45099662	45099892
ENSE00000942167	45099383	45099482
ENSE00000942171	45095828	45096060
ENSE00001121269	45094936	45095091
ENSE00001121297	45097614	45097741
ENSE00001121326	45100050	45100228
ENSE00001121339	45101205	45101274
ENSE00001121414	45108789	45108952
ENSE00001121420	45109524	45109626
ENSE00001121426	45109890	45109980
ENSE00001526031	45113973	45114172
ENSE00001600581	45108047	45108222
ENSE00001617465	45097238	45097391
ENSE00001621462	45111768	45111955
ENSE00001707606	45098009	45098058
ENSE00001719940	45094563	45094691
ENSE00001788032	45111384	45111585
ENSE00001794894	45095437	45095595
ENSE00001804668	45111111	45111277
ENSE00001886095	45092650	45094272
ENSE00003488387	45105643	45105828
ENSE00003489286	45106125	45106327
ENSE00003494642	45113342	45113425
ENSE00003499084	45103960	45104053
ENSE00003520975	45106528	45106641
ENSE00003544165	45110650	45110710
ENSE00003545263	45104140	45104365
ENSE00003560260	45112987	45113076
ENSE00003573290	45112554	45112718
ENSE00003619162	45107345	45107463
ENSE00003622497	45106832	45106969
ENSE00003691300	45110428	45110524

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 97.73.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1344 / max 549.1705, expressed in 108 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149681	0.9795	101
149682	0.1549	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	97.73	gold quality
nasal cavity epithelium	UBERON:0005384	97.64	gold quality
palpebral conjunctiva	UBERON:0001812	97.28	gold quality
right lobe of thyroid gland	UBERON:0001119	96.37	gold quality
left lobe of thyroid gland	UBERON:0001120	95.33	gold quality
thyroid gland	UBERON:0002046	95.27	gold quality
mucosa of stomach	UBERON:0001199	93.91	gold quality
lower esophagus mucosa	UBERON:0035834	93.30	gold quality
islet of Langerhans	UBERON:0000006	89.99	gold quality
vermiform appendix	UBERON:0001154	88.15	gold quality
esophagus squamous epithelium	UBERON:0006920	87.29	gold quality
epithelium of esophagus	UBERON:0001976	87.07	gold quality
esophagus mucosa	UBERON:0002469	86.90	gold quality
sperm	CL:0000019	85.44	gold quality
epithelial cell of pancreas	CL:0000083	85.41	gold quality
squamous epithelium	UBERON:0006914	84.27	gold quality
vagina	UBERON:0000996	84.00	gold quality
nasal cavity mucosa	UBERON:0001826	83.99	gold quality
epithelium of nasopharynx	UBERON:0001951	83.44	gold quality
type B pancreatic cell	CL:0000169	83.42	gold quality
oral cavity	UBERON:0000167	83.01	gold quality
male germ cell	CL:0000015	82.44	gold quality
cervix epithelium	UBERON:0004801	82.43	gold quality
gingiva	UBERON:0001828	82.27	gold quality
tongue squamous epithelium	UBERON:0006919	81.76	silver quality
gingival epithelium	UBERON:0001949	81.35	gold quality
urinary bladder	UBERON:0001255	81.33	gold quality
pharyngeal mucosa	UBERON:0000355	81.29	gold quality
caecum	UBERON:0001153	81.13	gold quality
body of stomach	UBERON:0001161	80.53	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	3361.33
E-CURD-88	yes	2724.56
E-CURD-79	yes	2079.08
E-MTAB-9221	yes	1884.43
E-MTAB-8142	yes	103.88
E-MTAB-6701	yes	29.60
E-HCAD-1	yes	18.47
E-ANND-3	yes	17.84
E-GEOD-83139	yes	10.92
E-CURD-135	no	3942.68
E-MTAB-8495	no	1404.06
E-MTAB-6108	no	568.94
E-MTAB-9689	no	114.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, HAND2, PAX8, STAT1

miRNA regulators (miRDB)

83 targeting DUOX2, 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-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084

Literature-anchored findings (GeneRIF, showing 40)

• the dual oxidase 2 N-terminal region is targeted to the plasma membrane (PMID:15150274)
• Expression of dual oxidase 2 in human colon and Caco-2 cells. (PMID:15591162)
• These data suggest that Duox1 and 2 are the major NADPH oxidases expressed in airway epithelia and therefore contributors of hydrogen peroxide production in the airway lumen. (PMID:15677770)
• post-translational modifications during the maturation process of Duox2 could be implicated in the mechanism of H2O2 formation by favoring intramolecular superoxide dismutation (PMID:15972824)
• Results demonstrate the regulation of Duox1 and 2 expression by Th1 and Th2 cytokines, and suggest a mechanism by which ROS production can be regulated in the respiratory tract as part of the host defense response. (PMID:16111680)
• Heterozygous mutations in the DUOX2 gene are responsible for iodide organification defect and congenital hypothyroidism. (PMID:16322276)
• In conclusion, incubation of normal or GD thyrocytes with Th1 cytokines induces a significant reduction in TSH-increased expression of both TPO and ThOXs, an effect partially mediated by NO. (PMID:16478776)
• co-expression with DUOXA2, an ER-resident transmembrane protein, allows ER-to-Golgi transition, maturation, and translocation to the plasma membrane of functional DUOX2 in a heterologous system (PMID:16651268)
• DUOXA2 allows rapid ER exit of folded DUOX2 or enhanced degradation of mutant DUOX2 proteins not competent for ER exit. (PMID:17374849)
• Analysis of point mutations opens possibility to ascertain whether transiency or permanency of DUOX2 phenotypes relate to monoallelic or biallelic inactivation of gene, or if degree of pathogenic severity of mutations may also influence outcome. (Review) (PMID:17684392)
• Results imply that the airway expression of Duox2 is diversely associated with smoking and chronic obstructive pulmonary disease. (PMID:18177232)
• Results suggest that an area on chromosome 15 that includes DUOX1, DUOX2, and their maturation factors is a frequent target for epigenetic silencing in lung cancer. (PMID:18281478)
• Loss of DUOX2 activity results in transient congenital hypothyroidism and transient congenital hypothyroidism caused by DUOX2 mutations is inherited as an autosomal recessive trait. (PMID:18765513)
• Activation of dual oxidases Duox1 and Duox2: differential regulation mediated by camp-dependent protein kinase and protein kinase C-dependent phosphorylation. (PMID:19144650)
• Heterodimerization controls localization of Duox-DuoxA NADPH oxidases in airway cells. (PMID:19339556)
• DUOX2 and NOD2 cooperatively facilitate antibacterial action. (PMID:19759286)
• Two new mutations in DUOX2 gene responsible for the partial deficit in the organification process of the thyroid gland are identified. (PMID:19789206)
• TPO binds to dualoxidases;defects in this association could impair thyroid hormone synthesis and lead to thyroid insufficiency and cell damage. (PMID:19952225)
• IFNgamma-mediated DUOX2 expression was regulated by a STAT-independent, JAK-independent pathway. (PMID:20381453)
• for respiratory epithelial cells, all-trans retinoic acid is important in the regulation of DUOX2 expression, function, and rhinovirus-mediated DUOX2 inducibility. (PMID:20511343)
• DUOX2 regulates cell cycle entry via a p53-dependent pathway. (PMID:20531308)
• Thyroid peroxidase consumes hydrogen peroxide produced by DUOX2, decreasing the availability of this substance at the apical membrane of thyrocytes. (PMID:20826581)
• Duox2-mediated signaling via reactive oxygen species participates in polyinosinic-polycytidylic acid-mediated type 1 tumor necrosis factor receptor (TNFR1) shedding downstream of receptor-interacting protein 1 (RIP1) airway epithelial cells (NCI-H292). (PMID:21148036)
• Up-regulation and sustained activation of Stat1 are essential for interferon-gamma (IFN-gamma)-induced dual oxidase 2 (Duox2) and dual oxidase A2 (DuoxA2) expression in human pancreatic cancer cell lines. (PMID:21321110)
• Two new mutations (Y1150C and A728T) and the deletion S965FsX994 were responsible for the deficit in the organification process and the phenotypes and three polymorphisms (H678R, P982A, and R701Q) were identified. (PMID:21565790)
• As was shown for DUOX1, the truncated DUOX2 domain purifies without a bound heme co-factor and displays no peroxidase activity. However, DUOX2(1-599) displays greater stability than DUOX1(1-593). (PMID:21704604)
• DUOX2 plays pivotal roles in TLR5-dependent inflammatory response of nasal airway epithelium. (PMID:21714724)
• Data show that comparing with adjacent non-neoplastic tissues, DUOX1, DUOX2, and NOX4 were expressed at higher frequencies in tumor specimens. (PMID:21915726)
• p.Arg376Trp mutation in DUOX2 was found in newborns of congenital hypothyroidism. (PMID:22336364)
• study reports DUOX 1 and 2 are expressed in neuroblastoma SK-N-BE cells as well as in an oligodendrocyte cell line (MO3-13); data unravel a novel mechanism of regulation of DUOX enzymes by reactive oxygen species and identify a circuitry linking NADPH oxidase activity to DUOX1 and 2 levels in neuroblastoma cells (PMID:22523549)
• Two functionally important single-nucleotide polymorphisms within the promoter differentially regulate DUOX2/DUOXA2 transcription in response to exogenous double-stranded DNA. (PMID:22592922)
• alterations of the DUOXA2 NH(2)-terminal domain modify DUOX2 activity triggering superoxide leaking (PMID:22814254)
• The present data open new perspectives for a better understanding of the pathophysiology of thyroid autoimmune diseases considering DUOX2-mediated oxidative damages. (PMID:23010498)
• Report shows that ROS levels in PC3 cells are constitutively maintained by DUOX 1 and 2 enzymes, and these ROS positively regulate AKT signalling through inactivating phosphatases, leading to increased resistance to apoptosis. (PMID:23225414)
• upregulated in chronic rhinosinusitis as a part of inflammatory response (PMID:23281318)
• The dramatic increase in reactive oxygen species induced in pancreatic cancer cells by the combination of lipopolysaccharide and interferon-gamma depends critically on the upregulation of, and signaling through, the Toll-like receptor (TLR)4 pathway. (PMID:23296709)
• Study indicates a complex profile of protein interactions required for activity and localization of the DUOX1 and DOOX2 enzymes. (PMID:23362256)
• Duox2 was expressed at elevated levels in many human cancers, most notably tumors of the prostate, lung, colon and breast. (PMID:23404210)
• p.G488R missense mutation in the DUOX2 gene of the congenital hypothyroidism patients is associated with thyroid dysfunction that presents during the neonatal period. (PMID:23457309)
• A key function of DUOX2 in the establishment of a late antiviral state triggered by the synergistic autocrine/paracrine action of IFNbeta and TNFalpha secreted during respiratory virus infection. (PMID:23545780)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Duox2	ENSMUSG00000068452
rattus_norvegicus	Duox2	ENSRNOG00000017395

Paralogs (6): NOX1 (ENSG00000007952), NOX3 (ENSG00000074771), NOX4 (ENSG00000086991), DUOX1 (ENSG00000137857), CYBB (ENSG00000165168), NOX5 (ENSG00000255346)

Protein

Protein identifiers

Dual oxidase 2 — Q9NRD8 (reviewed: Q9NRD8)

Alternative names: Large NOX 2, Long NOX 2, NADH/NADPH thyroid oxidase p138-tox, NADPH oxidase/peroxidase DUOX2, NADPH thyroid oxidase 2, Thyroid oxidase 2, p138 thyroid oxidase

All UniProt accessions (2): Q9NRD8, X6RAN8

UniProt curated annotations — full annotation on UniProt →

Function. Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormone synthesis. Also required for lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. Synthesizes NAADP from its reduced NAADPH form which promotes Ca(2+) signaling during T cell activation. May have its own peroxidase activity through its N-terminal peroxidase-like domain.

Subunit / interactions. Heterodimer with DUOXA2; disulfide-linked. Interacts with TXNDC11, TPO and CYBA.

Subcellular location. Apical cell membrane. Cell junction.

Tissue specificity. Expressed in colon, small intestine, duodenum and tracheal surface epithelial cells (at protein level). Expressed in thyrocytes. Also detected in kidney, liver, lung, pancreas, prostate, salivary glands, rectum and testis.

Post-translational modifications. N-glycosylated.

Disease relevance. Thyroid dyshormonogenesis 6 (TDH6) [MIM:607200] A disorder due to a defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete. The disease is caused by variants affecting the gene represented in this entry. Defects in DUOX2 may play a role in the pathogenesis of very early onset inflammatory bowel disease (VEOIBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology diagnosed before 6 years of age. VEOIBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but the phenotype of children with onset of Crohn disease occurring younger than the age of 10 is predominantly colonic, with a lower risk of ileal disease. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.

Activity regulation. Peroxidase activity is inhibited by aminobenzohydrazide. The NADPH oxidase activity is calcium-dependent.

Induction. By forskolin, thyrotropin and the Th1-specific cytokine IFNG/IFN-gamma.

Pathway. Hormone biosynthesis; thyroid hormone biosynthesis.

Similarity. In the N-terminal section; belongs to the peroxidase family.

RefSeq proteins (2): NP_001350640, NP_054799 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR010255	Haem_peroxidase_sf	Homologous_superfamily
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013112	FAD-bd_8	Domain
IPR013121	Fe_red_NAD-bd_6	Domain
IPR013130	Fe3_Rdtase_TM_dom	Domain
IPR017927	FAD-bd_FR_type	Domain
IPR017938	Riboflavin_synthase-like_b-brl	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR019791	Haem_peroxidase_animal	Family
IPR034821	DUOX_peroxidase	Domain
IPR037120	Haem_peroxidase_sf_animal	Homologous_superfamily
IPR039261	FNR_nucleotide-bd	Homologous_superfamily
IPR050369	RBOH/FRE	Family

Pfam: PF00036, PF01794, PF03098, PF08022, PF08030, PF13833

Enzyme classification (BRENDA):

• EC 1.6.3.1 — NAD(P)H oxidase (H2O2-forming) (BRENDA: 39 organisms, 58 substrates, 307 inhibitors, 10 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.01–0.1	7
NADH	0.1–0.413	3

Catalyzed reactions (Rhea), 3 shown:

• NADPH + O2 + H(+) = H2O2 + NADP(+) (RHEA:11260)
• NADH + O2 + H(+) = H2O2 + NAD(+) (RHEA:11264)
• NAADPH + O2 + H(+) = NAADP(+) + H2O2 (RHEA:86235)

UniProt features (51 total): binding site 9, sequence variant 8, topological domain 7, transmembrane region 7, domain 5, glycosylation site 5, region of interest 3, disulfide bond 3, sequence conflict 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRD8-F1	84.37	0.53

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 (9): 832; 834; 836; 838; 843; 868; 870; 872; 879

Disulfide bonds (3): 124–1162, 568, 582

Glycosylation sites (5): 100, 348, 382, 455, 537

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-209968	Thyroxine biosynthesis

MSigDB gene sets: 221 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_RESPONSE_TO_PEPTIDE, LFA1_Q6, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_SUPEROXIDE_METABOLIC_PROCESS, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, GOBP_WOUND_HEALING, GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, MODULE_205, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE

GO Biological Process (23): thyroid hormone generation (GO:0006590), defense response (GO:0006952), response to oxidative stress (GO:0006979), response to virus (GO:0009615), cytokine-mediated signaling pathway (GO:0019221), cuticle development (GO:0042335), hormone biosynthetic process (GO:0042446), superoxide anion generation (GO:0042554), hydrogen peroxide catabolic process (GO:0042744), hydrogen peroxide biosynthetic process (GO:0050665), response to cAMP (GO:0051591), positive regulation of wound healing (GO:0090303), positive regulation of cell motility (GO:2000147), fertilization (GO:0009566), bone mineralization (GO:0030282), thyroid gland development (GO:0030878), multicellular organism growth (GO:0035264), thyroid hormone metabolic process (GO:0042403), hormone metabolic process (GO:0042445), inner ear development (GO:0048839), adenohypophysis morphogenesis (GO:0048855), cellular response to cytokine stimulus (GO:0071345), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (8): peroxidase activity (GO:0004601), calcium ion binding (GO:0005509), NAD(P)H oxidase H2O2-forming activity (GO:0016174), superoxide-generating NAD(P)H oxidase activity (GO:0016175), heme binding (GO:0020037), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (11): endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), apical plasma membrane (GO:0016324), cell leading edge (GO:0031252), NADPH oxidase complex (GO:0043020), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), anchoring junction (GO:0070161), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amine-derived hormones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
response to stress	2
anatomical structure development	2
hormone metabolic process	2
hydrogen peroxide metabolic process	2
oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor	2
cytoplasm	2
thyroid hormone metabolic process	1
response to other organism	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
multicellular organism development	1
biosynthetic process	1
superoxide metabolic process	1
catabolic process	1
reactive oxygen species biosynthetic process	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
positive regulation of locomotion	1
positive regulation of cellular process	1
cell motility	1
regulation of cell motility	1
sexual reproduction	1
reproductive process	1
ossification	1
biomineral tissue development	1
endocrine system development	1
gland development	1
multicellular organismal process	1
developmental growth	1
modified amino acid metabolic process	1
phenol-containing compound metabolic process	1
metabolic process	1
regulation of hormone levels	1
ear development	1
antioxidant activity	1

Protein interactions and networks

STRING

1583 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUOX2	DUOXA2	Q1HG44	997
DUOX2	DUOXA1	Q1HG43	972
DUOX2	NOX1	Q9Y5S8	952
DUOX2	IYD	Q6PHW0	929
DUOX2	NCF2	P19878	912
DUOX2	NOX3	Q9HBY0	888
DUOX2	CYBA	P13498	881
DUOX2	NOX4	Q9NPH5	842
DUOX2	NCF4	Q15080	830
DUOX2	NOX5	Q96PH1	828
DUOX2	SLC26A4	O43511	817
DUOX2	NCF1	P14598	815
DUOX2	SLC5A5	Q92911	794
DUOX2	NOD2	Q9HC29	755
DUOX2	CYBB	P04839	748

IntAct

26 interactions, top by confidence:

A	B	Type	Score
DUOX2	DUOXA2	psi-mi:“MI:0915”(physical association)	0.590
TXNDC11	DUOX2	psi-mi:“MI:0915”(physical association)	0.400
FBXW7	DUOX2	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	DUOX2	psi-mi:“MI:2364”(proximity)	0.270
DUOX2	SMAD4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	DUOX2	psi-mi:“MI:2364”(proximity)	0.270
SPOP	DUOX2	psi-mi:“MI:2364”(proximity)	0.270
DUOX2	SPOP	psi-mi:“MI:2364”(proximity)	0.270
EGFR	DUOX2	psi-mi:“MI:2364”(proximity)	0.270
DUOX2	PTEN	psi-mi:“MI:2364”(proximity)	0.270
DUOX2	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
DUOX2	TP53	psi-mi:“MI:2364”(proximity)	0.270
DUOX2	AKT1	psi-mi:“MI:2364”(proximity)	0.270
DUOX2	BRAF	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (30): DUOX2 (Affinity Capture-MS), DUOX2 (Affinity Capture-MS), DUOX2 (Affinity Capture-MS), DUOX2 (Co-localization), DUOX2 (Co-localization), DUOX2 (Co-localization), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS)), DUOX2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A6H757, A6QPN6, B1H1P9, B3SP85, F1N2K1, O46559, O94952, O95479, P22413, P56201, P57075, P98192, Q13219, Q3U3W5, Q3V3E1, Q499T2, Q502B3, Q53H76, Q5E9H0, Q5NDE3, Q5NDE4, Q5R5S1, Q5R5X9, Q5R8C0, Q5RBQ5, Q6AYG3, Q6P2P2, Q7TNH6, Q865R1, Q86TP1, Q86UX2, Q8BGG7, Q8BP40, Q8CFX1, Q8CIY2, Q8HZK2, Q8HZK3, Q8IUF8, Q8IYR2, Q8R4K8

Diamond homologs: O46522, O48538, O81209, O81210, O81211, P04839, P52649, Q2HXK9, Q2HXL0, Q3KTM0, Q5ZAJ0, Q61093, Q6J2K5, Q86GL4, Q8CIY2, Q8HZK2, Q8HZK3, Q8RWS6, Q8VY13, Q8W110, Q948T9, Q948U0, Q95L74, Q9ES45, Q9FIJ0, Q9FJD6, Q9FLW2, Q9LZU9, Q9MZF4, Q9NRD8, Q9NRD9, Q9SBI0, Q9SUT8, Q9SW17, Q9WV87, Q9XYS3, Q9Y5S8, A8WQH2, B3A0Q8, G5EG78

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DUOX2	up-regulates	ROS
DUOX2	“up-regulates quantity”	superoxide	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

2360 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	120
Likely pathogenic	83
Uncertain significance	993
Likely benign	887
Benign	79

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071547	NM_001363711.2(DUOX2):c.2101C>T (p.Arg701Ter)	Pathogenic
1322789	NM_001363711.2(DUOX2):c.2921+2T>C	Pathogenic
1322790	NM_001363711.2(DUOX2):c.2000del (p.Leu667fs)	Pathogenic
1369058	NM_001363711.2(DUOX2):c.2752G>T (p.Glu918Ter)	Pathogenic
1378081	NM_001363711.2(DUOX2):c.2749dup (p.Glu917fs)	Pathogenic
1380164	NM_001363711.2(DUOX2):c.1894_1895del (p.Lys632fs)	Pathogenic
1390762	NM_001363711.2(DUOX2):c.152dup (p.Ala52fs)	Pathogenic
1404956	NM_001363711.2(DUOX2):c.1153C>T (p.Gln385Ter)	Pathogenic
1415646	NM_001363711.2(DUOX2):c.1461_1462delinsCA (p.Gly488Arg)	Pathogenic
1418394	NM_001363711.2(DUOX2):c.430C>T (p.Gln144Ter)	Pathogenic
1452992	NM_001363711.2(DUOX2):c.3486C>A (p.Cys1162Ter)	Pathogenic
1454809	NM_001363711.2(DUOX2):c.1741C>T (p.Gln581Ter)	Pathogenic
1458737	NM_001363711.2(DUOX2):c.2654G>A (p.Arg885Gln)	Pathogenic
1466218	NM_001363711.2(DUOX2):c.4522C>T (p.Gln1508Ter)	Pathogenic
1687299	NM_001363711.2(DUOX2):c.790del (p.Leu264fs)	Pathogenic
1956595	NM_001363711.2(DUOX2):c.3134_3135del (p.Val1045fs)	Pathogenic
1970476	NM_001363711.2(DUOX2):c.2800G>T (p.Glu934Ter)	Pathogenic
1985409	NM_001363711.2(DUOX2):c.1247del (p.Gly416fs)	Pathogenic
2000977	NM_001363711.2(DUOX2):c.88dup (p.Ser30fs)	Pathogenic
2005887	NM_001363711.2(DUOX2):c.1327C>T (p.Gln443Ter)	Pathogenic
2020594	NM_001363711.2(DUOX2):c.2071C>T (p.Gln691Ter)	Pathogenic
2029153	NM_001363711.2(DUOX2):c.1726dup (p.Thr576fs)	Pathogenic
2030421	NM_001363711.2(DUOX2):c.2972del (p.Gly991fs)	Pathogenic
2041343	NM_001363711.2(DUOX2):c.3546G>A (p.Trp1182Ter)	Pathogenic
2053940	NM_001363711.2(DUOX2):c.2887C>T (p.Arg963Ter)	Pathogenic
2081186	NM_001363711.2(DUOX2):c.1180_1181del (p.Met394fs)	Pathogenic
2081463	NM_001363711.2(DUOX2):c.2869_2870insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCAGAGATATCTTTA (p.Lys957delinsIlePhePhePhePhePhePheXaaXaaXaaXaaAspLeuMetIleHisProProArgProProLysValLeuGlyLeuGlnAlaTer)	Pathogenic
2087425	NM_001363711.2(DUOX2):c.2728G>T (p.Glu910Ter)	Pathogenic
2118971	NM_001363711.2(DUOX2):c.16_19dup (p.Glu7fs)	Pathogenic
2119413	NM_001363711.2(DUOX2):c.1554G>A (p.Trp518Ter)	Pathogenic

SpliceAI

4949 predictions. Top by Δscore:

Variant	Effect	Δscore
15:45094558:CTGA:C	donor_loss	1.0000
15:45094560:GAC:G	donor_loss	1.0000
15:45094576:T:TA	donor_gain	1.0000
15:45094687:ATGTA:A	acceptor_gain	1.0000
15:45094688:TGTA:T	acceptor_gain	1.0000
15:45094689:G:C	acceptor_gain	1.0000
15:45094689:GTA:G	acceptor_gain	1.0000
15:45094690:TA:T	acceptor_gain	1.0000
15:45094690:TAC:T	acceptor_loss	1.0000
15:45094691:ACT:A	acceptor_loss	1.0000
15:45094692:C:CC	acceptor_gain	1.0000
15:45094692:C:T	acceptor_loss	1.0000
15:45094699:C:CT	acceptor_gain	1.0000
15:45094701:C:CT	acceptor_gain	1.0000
15:45094702:A:T	acceptor_gain	1.0000
15:45094717:C:CT	acceptor_gain	1.0000
15:45094934:A:AC	donor_gain	1.0000
15:45094935:C:CA	donor_gain	1.0000
15:45094935:CTAG:C	donor_gain	1.0000
15:45094947:T:TA	donor_gain	1.0000
15:45094962:T:TA	donor_gain	1.0000
15:45095088:AGAT:A	acceptor_gain	1.0000
15:45095092:C:CA	acceptor_loss	1.0000
15:45095092:C:CC	acceptor_gain	1.0000
15:45095875:C:CA	donor_gain	1.0000
15:45097232:TGATA:T	donor_loss	1.0000
15:45097233:GATAC:G	donor_loss	1.0000
15:45097235:TA:T	donor_loss	1.0000
15:45097236:A:AT	donor_loss	1.0000
15:45097332:C:CT	acceptor_gain	1.0000

AlphaMissense

10114 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:45094249:G:C	S1516R	0.998
15:45094249:G:T	S1516R	0.998
15:45094251:T:G	S1516R	0.998
15:45095049:A:G	W1428R	0.998
15:45095049:A:T	W1428R	0.998
15:45099472:A:C	S1142R	0.998
15:45099472:A:T	S1142R	0.998
15:45099474:T:G	S1142R	0.998
15:45095962:G:C	H1316D	0.997
15:45096004:A:G	W1302R	0.997
15:45096004:A:T	W1302R	0.997
15:45096048:A:G	L1287P	0.997
15:45097653:G:C	F1218L	0.997
15:45097653:G:T	F1218L	0.997
15:45097655:A:G	F1218L	0.997
15:45095079:A:G	W1418R	0.996
15:45095079:A:T	W1418R	0.996
15:45095893:A:G	W1339R	0.996
15:45095893:A:T	W1339R	0.996
15:45099698:G:C	H1127D	0.996
15:45099826:C:G	R1084P	0.996
15:45095489:A:G	L1396P	0.995
15:45095556:A:G	W1374R	0.995
15:45095556:A:T	W1374R	0.995
15:45096002:C:A	W1302C	0.995
15:45096002:C:G	W1302C	0.995
15:45097327:G:C	P1253R	0.995
15:45099748:C:G	R1110P	0.995
15:45099810:G:C	S1089R	0.995
15:45099810:G:T	S1089R	0.995

dbSNP variants (sampled 300 via entrez): RS1000024283 (15:45093871 G>C,T), RS1000026180 (15:45104813 A>ATTTATTGTT), RS1000091464 (15:45106085 G>A,T), RS1000349622 (15:45096626 A>G,T), RS1000630013 (15:45095054 A>G), RS1000680012 (15:45113560 T>C), RS1000696834 (15:45096215 C>G,T), RS1000975279 (15:45105159 T>C), RS1001086343 (15:45095221 C>A,G), RS1001113331 (15:45093976 T>C,G), RS1001164227 (15:45099868 G>A,T), RS1001214959 (15:45098415 T>C), RS1001393949 (15:45092589 C>T), RS1001411991 (15:45092196 G>A), RS1001808723 (15:45103169 G>A)

Disease associations

OMIM: gene MIM:606759 | disease phenotypes: MIM:607200, MIM:274400, MIM:213600, MIM:606656, MIM:615397, MIM:612718

GenCC curated gene-disease

Disease	Classification	Inheritance
thyroid dyshormonogenesis 6	Definitive	Autosomal recessive
inflammatory bowel disease	Strong	Autosomal recessive
familial thyroid dyshormonogenesis	Supportive	Autosomal recessive

Mondo (7): thyroid dyshormonogenesis 6 (MONDO:0011792), familial thyroid dyshormonogenesis (MONDO:0010132), congenital hypothyroidism (MONDO:0018612), basal ganglia calcification, idiopathic, 1 (MONDO:0024538), Meckel syndrome, type 11 (MONDO:0014164), AGAT deficiency (MONDO:0012996), inflammatory bowel disease (MONDO:0005265)

Orphanet (6): Genetic transient congenital hypothyroidism (Orphanet:226316), Familial thyroid dyshormonogenesis (Orphanet:95716), Congenital hypothyroidism (Orphanet:442), Bilateral striopallidodentate calcinosis (Orphanet:1980), Meckel syndrome (Orphanet:564), L-Arginine:glycine amidinotransferase deficiency (Orphanet:35704)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000270	Delayed cranial suture closure
HP:0000282	Facial edema
HP:0000407	Sensorineural hearing impairment
HP:0000821	Hypothyroidism
HP:0000851	Congenital hypothyroidism
HP:0000853	Goiter
HP:0000969	Edema
HP:0001070	Mottled pigmentation
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001262	Excessive daytime somnolence
HP:0001265	Hyporeflexia
HP:0001537	Umbilical hernia
HP:0001615	Hoarse cry
HP:0001662	Bradycardia
HP:0002019	Constipation
HP:0002045	Hypothermia
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration
HP:0003265	Neonatal hyperbilirubinemia
HP:0004491	Large posterior fontanelle
HP:0005280	Depressed nasal bridge
HP:0005930	Abnormal epiphysis morphology
HP:0005990	Thyroid hypoplasia
HP:0006579	Prolonged neonatal jaundice
HP:0008263	Thyroid defect in oxidation and organification of iodide
HP:0008828	Delayed proximal femoral epiphyseal ossification
HP:0008872	Feeding difficulties in infancy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST011366_3	Iron status biomarkers (transferrin saturation)	6.000000e-12
GCST011367_11	Iron status biomarkers (iron levels)	1.000000e-08
GCST011368_4	Iron status biomarkers (total iron binding capacity)	4.000000e-19
GCST011369_23	Iron status biomarkers (ferritin levels)	1.000000e-113

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006333	transferrin saturation measurement
EFO:0006334	total iron binding capacity
EFO:0004459	ferritin measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D003409	Congenital Hypothyroidism	C05.116.099.343.347; C05.116.132.256; C16.320.240.625; C19.297.155; C19.874.482.281
D015212	Inflammatory Bowel Diseases	C06.405.205.731; C06.405.469.432
C567192	Arginine-Glycine Amidinotransferase Deficiency (supp.)
C537657	Basal ganglia calcification, idiopathic 2 (supp.)
C564766	Thyroid Dyshormonogenesis 1 (supp.)
C564608	Thyroid Dyshormonogenesis 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3293 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — NADPH oxidases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
NSC 780521	Inhibition	6.11	pIC50

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.57	IC50	2700	nM	CHEMBL4210329

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(3-benzyltriazolo[4,5-d]pyrimidin-7-yl)sulfanyl-1,3-benzoxazole	2013287: Inhibition of human DUOX2 transfected in HEK cells assessed as PMA-induced hydrogen peroxide production preincubated for 15 mins and measured after 10 mins by Amplex-red based fluorescence assay	ic50	2.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	3
Aflatoxin B1	affects expression, increases expression	3
sodium arsenite	affects methylation, affects reaction, increases expression	2
monomethylarsonous acid	decreases expression	2
Paraquat	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression	2
methyl vanillate	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
cerous chloride	affects cotreatment, increases expression	1
lanthanum chloride	affects cotreatment, increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
cyfluthrin	increases expression	1
entinostat	increases expression	1
lipopolysaccharide, Escherichia coli O111 B4	affects reaction, decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Amphotericin B	increases expression	1
Deferoxamine	decreases reaction, increases expression	1
Diethylhexyl Phthalate	decreases reaction, increases expression, affects reaction	1
Glucose	decreases expression	1
Gold	affects binding, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5367020	Binding	Inhibition of human DUOX2 transfected in HEK cells assessed as PMA-induced hydrogen peroxide production preincubated for 15 mins and measured after 10 mins by Amplex-red based fluorescence assay	NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00167882	PHASE4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00205062	PHASE4	TERMINATED	Positron Emission Tomography (PET)-Computed Tomography (CT) in Inflammatory Bowel Disease (IBD)
NCT00567593	PHASE4	COMPLETED	Gene Regulation by Thiazolidinediones
NCT00746395	PHASE4	COMPLETED	Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy
NCT01034358	PHASE4	COMPLETED	Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease
NCT01056913	PHASE4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01067547	PHASE4	COMPLETED	A Trial of Iron Replacement in Patients With Iron Deficiency.
NCT01341808	PHASE4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01908283	PHASE4	COMPLETED	Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
NCT01934088	PHASE4	COMPLETED	Satisfaction With Nurse Administered Propofol Sedation vs. Midazolam With Fentanyl Sedation for Endoscopy
NCT02162862	PHASE4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02248337	PHASE4	COMPLETED	Low Volume Colon Preparation for IBD
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02392286	PHASE4	TERMINATED	Corticosteroid Dosage for Crohn’s Disease Flare
NCT02437591	PHASE4	COMPLETED	Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
NCT02453776	PHASE4	COMPLETED	Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
NCT02461758	PHASE4	COMPLETED	Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
NCT02566889	PHASE4	TERMINATED	An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
NCT02774057	PHASE4	UNKNOWN	Trial of Captafer® vs. Oral Iron Sulfate in the Treatment of Iron Deficiency Anemia in Patients With IBD
NCT02806206	PHASE4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT02946203	PHASE4	COMPLETED	Comparison of VoLumen and Breeza Oral Contrast Agents in Pediatric Patients
NCT02994836	PHASE4	COMPLETED	GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )
NCT03220841	PHASE4	UNKNOWN	Stricture Definition and Treatment (STRIDENT) Drug Therapy Study
NCT03351972	PHASE4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03466983	PHASE4	COMPLETED	A Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia Due to Inflammatory Bowel Disease
NCT03591770	PHASE4	TERMINATED	Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
NCT03629379	PHASE4	COMPLETED	Response to Ustekinumab for Anti-tnf Induced Psoriasiform Skin Lesions
NCT03723447	PHASE4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT03798691	PHASE4	COMPLETED	Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab
NCT03860012	PHASE4	UNKNOWN	Folic Acid in Pediatric Inflammatory Bowel Disease
NCT03885713	PHASE4	COMPLETED	Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease
NCT03917303	PHASE4	RECRUITING	Control Crohn Safe Trial
NCT04045782	PHASE4	COMPLETED	Evaluation of the Safety and Effectiveness of Switching From Humira® to Imraldi® in Flanders
NCT04304950	PHASE4	COMPLETED	Chronotherapy in Inflammatory Bowel Disease
NCT04626947	PHASE4	TERMINATED	Prevention of Recurrent Clostridium Difficile Infection (CDI) in Patients With Inflammatory Bowel Disease (IBD).
NCT04646187	PHASE4	ENROLLING_BY_INVITATION	De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
NCT04835506	PHASE4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT04982172	PHASE4	COMPLETED	Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
NCT05180175	PHASE4	COMPLETED	The Nordic IBD Treatment Strategy Trial
NCT05280405	PHASE4	UNKNOWN	Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study