DUT

Summary

DUT (deoxyuridine triphosphatase, HGNC:3078) is a protein-coding gene on chromosome 15q21.1, encoding Deoxyuridine 5’-triphosphate nucleotidohydrolase, mitochondrial (P33316). Catalyzes the cleavage of 2’-deoxyuridine 5’-triphosphate (dUTP) into 2’-deoxyuridine 5’-monophosphate (dUMP) and inorganic pyrophosphate and through its action efficiently prevents uracil misincorporation into DNA and at the same time provides dUMP, the substrate for de novo th…. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

This gene encodes an essential enzyme of nucleotide metabolism. The encoded protein forms a ubiquitous, homotetrameric enzyme that hydrolyzes dUTP to dUMP and pyrophosphate. This reaction serves two cellular purposes: providing a precursor (dUMP) for the synthesis of thymine nucleotides needed for DNA replication, and limiting intracellular pools of dUTP. Elevated levels of dUTP lead to increased incorporation of uracil into DNA, which induces extensive excision repair mediated by uracil glycosylase. This repair process, resulting in the removal and reincorporation of dUTP, is self-defeating and leads to DNA fragmentation and cell death. Alternative splicing of this gene leads to different isoforms that localize to either the mitochondrion or nucleus. A related pseudogene is located on chromosome 19.

Source: NCBI Gene 1854 — RefSeq curated summary.

At a glance

• Gene–disease (curated): bone marrow failure and diabetes mellitus syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 28 total — 2 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 15 tissues, sQTL in 21 (q < 0.05)
• Phenotypes (HPO): 11
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.68 (unconstrained)
• MANE Select transcript: NM_001025248
• Interaction hub: 1,872 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3078
Approved symbol	DUT
Name	deoxyuridine triphosphatase
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	dUTPase
Ensembl gene	ENSG00000128951
Ensembl biotype	protein_coding
OMIM	601266
Entrez	1854

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 7 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000331200

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 5, TSL 3: 3, TSL 5: 1

ENST00000331200, ENST00000455976, ENST00000558367, ENST00000558472, ENST00000558813, ENST00000558978, ENST00000559416, ENST00000559540, ENST00000559852, ENST00000559935, ENST00000561350, ENST00000915906, ENST00000949573, ENST00000975445, ENST00000975447, ENST00000975448, ENST00001036282, ENST00001036283, ENST00001036285

RefSeq mRNA: 4 — MANE Select: NM_001025248 NM_001025248, NM_001025249, NM_001330286, NM_001948

CCDS: CCDS32231, CCDS45255, CCDS45256, CCDS81879

Canonical transcript exons

ENST00000331200 — 7 exons

Exon	Start	End
ENSE00000686853	48334417	48334508
ENSE00000686860	48341289	48341363
ENSE00001487133	48331429	48331795
ENSE00003541445	48332268	48332406
ENSE00003603862	48336046	48336090
ENSE00003667790	48341515	48341585
ENSE00004788236	48342022	48343373

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.6083 / max 653.9917, expressed in 1821 samples.

Highest expression (Bgee): pylorus, trabecular bone tissue, trigeminal ganglion, caput epididymis, urethra.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DUT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 36 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	3.1e-88	+0.75	15:48304516:T:C
Thyroid	sqtl	4.1e-15	-1.83	15:48340145:G:A
Nerve Tibial	sqtl	1.1e-11	+1.37	15:48340145:G:A
Testis	sqtl	5.9e-10	-1.67	15:48366503:A:G
Artery Aorta	sqtl	2.3e-08	+1.64	15:48340145:G:A
Adipose Subcutaneous	sqtl	3.4e-08	+1.20	15:48366503:A:G
Skin Sun Exposed Lower leg	sqtl	8.5e-07	+1.13	15:48340145:G:A
Spleen	sqtl	8.7e-07	+1.97	15:48340145:G:A
Esophagus Muscularis	sqtl	1.3e-06	+1.25	15:48340145:G:A
Lung	sqtl	4.9e-06	+1.15	15:48340145:G:A
Skin Sun Exposed Lower leg	eqtl	6.1e-06	+0.46	15:48384595:A:G
Artery Tibial	eqtl	1.1e-05	-0.17	15:48292686:C:T
Muscle Skeletal	sqtl	1.3e-05	+1.04	15:48340145:G:A
Nerve Tibial	eqtl	1.5e-05	+0.51	15:48384595:A:G
Esophagus Mucosa	eqtl	8.0e-05	+0.14	15:48383030:G:A
Adipose Subcutaneous	eqtl	1.9e-04	-0.17	15:48291640:C:A
Adipose Visceral Omentum	sqtl	2.1e-04	+1.17	15:48340145:G:A
Esophagus Mucosa	sqtl	3.5e-04	+0.98	15:48340145:G:A
Pituitary	eqtl	3.6e-04	-0.29	15:48284184:T:C
Skin Not Sun Exposed Suprapubic	eqtl	7.1e-04	+0.23	15:48282174:C:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
146548	48.0665	1583
146547	23.4368	1814
146546	1.5416	753
146545	0.5633	310

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pylorus	UBERON:0001166	99.44	gold quality
trabecular bone tissue	UBERON:0002483	99.31	gold quality
trigeminal ganglion	UBERON:0001675	99.20	gold quality
caput epididymis	UBERON:0004358	99.19	gold quality
urethra	UBERON:0000057	99.18	gold quality
superior surface of tongue	UBERON:0007371	99.18	gold quality
mammary duct	UBERON:0001765	99.09	gold quality
renal medulla	UBERON:0000362	99.07	gold quality
corpus epididymis	UBERON:0004359	98.98	gold quality
epithelium of mammary gland	UBERON:0003244	98.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.94	gold quality
cranial nerve II	UBERON:0000941	98.89	gold quality
penis	UBERON:0000989	98.87	gold quality
dorsal root ganglion	UBERON:0000044	98.83	gold quality
cauda epididymis	UBERON:0004360	98.81	gold quality
cervix squamous epithelium	UBERON:0006922	98.81	gold quality
adult organism	UBERON:0007023	98.80	gold quality
tibia	UBERON:0000979	98.78	gold quality
pericardium	UBERON:0002407	98.78	gold quality
cardia of stomach	UBERON:0001162	98.74	gold quality
synovial joint	UBERON:0002217	98.73	gold quality
endometrium	UBERON:0001295	98.72	gold quality
germinal epithelium of ovary	UBERON:0001304	98.72	gold quality
pharyngeal mucosa	UBERON:0000355	98.71	gold quality
skin of hip	UBERON:0001554	98.70	gold quality
tongue	UBERON:0001723	98.69	gold quality
inferior vagus X ganglion	UBERON:0005363	98.68	gold quality
oral cavity	UBERON:0000167	98.67	gold quality
parotid gland	UBERON:0001831	98.67	gold quality
nipple	UBERON:0002030	98.63	gold quality
seminal vesicle	UBERON:0000998	98.60	gold quality
blood vessel layer	UBERON:0004797	98.60	gold quality
pons	UBERON:0000988	98.57	gold quality
ventricular zone	UBERON:0003053	98.57	gold quality
superficial temporal artery	UBERON:0001614	98.55	gold quality
pigmented layer of retina	UBERON:0001782	98.55	gold quality
saphenous vein	UBERON:0007318	98.55	gold quality
superior vestibular nucleus	UBERON:0007227	98.54	gold quality
body of tongue	UBERON:0011876	98.53	gold quality
visceral pleura	UBERON:0002401	98.51	gold quality
ventral tegmental area	UBERON:0002691	98.51	gold quality
trachea	UBERON:0003126	98.50	gold quality
tendon of biceps brachii	UBERON:0008188	98.49	gold quality
calcaneal tendon	UBERON:0003701	98.47	gold quality
tendon	UBERON:0000043	98.45	gold quality
lower lobe of lung	UBERON:0008949	98.43	gold quality
vena cava	UBERON:0004087	98.42	gold quality
lateral globus pallidus	UBERON:0002476	98.40	gold quality
pleura	UBERON:0000977	98.31	gold quality
parietal pleura	UBERON:0002400	98.28	gold quality
ganglionic eminence	UBERON:0004023	98.28	gold quality
subthalamic nucleus	UBERON:0001906	98.26	gold quality
embryo	UBERON:0000922	98.25	gold quality
uterus	UBERON:0000995	98.20	gold quality
mammary gland	UBERON:0001911	98.20	gold quality
epithelium of nasopharynx	UBERON:0001951	98.18	gold quality
substantia nigra pars compacta	UBERON:0001965	98.18	gold quality
thoracic mammary gland	UBERON:0005200	98.18	gold quality
gingival epithelium	UBERON:0001949	98.17	gold quality
gingiva	UBERON:0001828	98.15	gold quality
layer of synovial tissue	UBERON:0007616	98.14	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.13	gold quality
globus pallidus	UBERON:0001875	98.10	gold quality
endocervix	UBERON:0000458	98.06	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.06	gold quality
thymus	UBERON:0002370	98.06	gold quality
right lobe of thyroid gland	UBERON:0001119	98.05	gold quality
body of uterus	UBERON:0009853	98.04	gold quality
left ovary	UBERON:0002119	98.03	gold quality
upper leg skin	UBERON:0004262	98.03	gold quality
periodontal ligament	UBERON:0008266	98.02	gold quality
medial globus pallidus	UBERON:0002477	98.00	gold quality
bone marrow	UBERON:0002371	97.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.98	gold quality
left lobe of thyroid gland	UBERON:0001120	97.96	gold quality
myometrium	UBERON:0001296	97.92	gold quality
thyroid gland	UBERON:0002046	97.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.90	gold quality
parietal lobe	UBERON:0001872	97.89	gold quality
right ovary	UBERON:0002118	97.88	gold quality
ovary	UBERON:0000992	97.85	gold quality
fundus of stomach	UBERON:0001160	97.85	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.84	gold quality
mammalian vulva	UBERON:0000997	97.83	gold quality
pituitary gland	UBERON:0000007	97.82	gold quality
lymph node	UBERON:0000029	97.81	gold quality
caecum	UBERON:0001153	97.81	gold quality
endometrium epithelium	UBERON:0004811	97.80	gold quality
right uterine tube	UBERON:0001302	97.79	gold quality
postcentral gyrus	UBERON:0002581	97.78	gold quality
mucosa of urinary bladder	UBERON:0001259	97.74	gold quality
female reproductive system	UBERON:0000474	97.73	gold quality
ectocervix	UBERON:0012249	97.71	gold quality
descending thoracic aorta	UBERON:0002345	97.66	gold quality
middle frontal gyrus	UBERON:0002702	97.65	gold quality
squamous epithelium	UBERON:0006914	97.59	gold quality
amniotic fluid	UBERON:0000173	97.57	gold quality
thoracic aorta	UBERON:0001515	97.57	gold quality
ascending aorta	UBERON:0001496	97.56	gold quality
jejunum	UBERON:0002115	97.53	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	1130.88
E-MTAB-10662	yes	1089.77
E-CURD-98	yes	876.54
E-MTAB-10485	yes	818.60
E-MTAB-9435	yes	772.87
E-CURD-114	yes	682.47
E-MTAB-10287	yes	652.37
E-MTAB-6379	yes	646.71
E-GEOD-125970	yes	398.02
E-HCAD-4	yes	156.23
E-CURD-112	yes	40.95
E-HCAD-5	yes	34.89
E-MTAB-9467	yes	31.65
E-CURD-122	yes	28.41
E-CURD-46	yes	25.07

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	153.7	high
Thymus	tissue	103.8
Lymph node	tissue	91.3	high
Tonsil	tissue	82.2	high
Pituitary gland	tissue	75.4
Vagina	tissue	74.7	medium
Ovary	tissue	62.1	medium
Adrenal gland	tissue	59.7	medium
Breast	tissue	58.5	medium
Appendix	tissue	58.2	medium
Choroid plexus	tissue	55.9
Adipose tissue	tissue	54.2	not detected
Skeletal muscle	tissue	54.2	low
Skin 1	tissue	52.3	medium
Salivary gland	tissue	52.2	medium
Thyroid gland	tissue	51.8	medium
Colon	tissue	50.4	medium
Nucleus accumbens	tissue	50.4
Spleen	tissue	50.2	medium
Stomach 1	tissue	50.0	medium
Heart muscle	tissue	49.6	low
Tongue	tissue	49.4
Endometrium 1	tissue	49.3	medium
Epididymis	tissue	46.9	low
Kidney	tissue	46.2	medium
Retina	tissue	45.5
Seminal vesicle	tissue	45.5	medium
Parathyroid gland	tissue	45.4	medium
Postcentral gyrus	tissue	44.9
Rectum	tissue	44.2	medium
Pons	tissue	44.1
Locus coeruleus	tissue	43.6
Putamen	tissue	43.5
Prostate	tissue	43.4	medium
Placenta	tissue	42.3	medium
Septum	tissue	42.0
Thalamus	tissue	41.7
Fallopian tube	tissue	41.4	medium
Basal ganglia	tissue	40.7	low
Spinal cord	tissue	40.5
Ventral forebrain	tissue	40.3
Superior colliculi	tissue	40.1
Small intestine	tissue	40.1	medium
Cervix	tissue	40.0	medium
Hypothalamus	tissue	40.0
Medulla oblongata	tissue	39.9
Cerebral cortex	tissue	38.8	low
Somatosensory cortex	tissue	38.8
Substantia nigra	tissue	38.5
Midbrain	tissue	38.2
Hippocampal formation	tissue	37.9
Smooth muscle	tissue	37.8	low
Pancreas	tissue	37.3	medium
Liver	tissue	37.3	low
Occipital cortex	tissue	37.3
Lung	tissue	37.0	low
Hippocampus	tissue	36.7	low
Periaqueductal gray	tissue	36.6
Temporal cortex	tissue	36.4
Testis	tissue	36.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (83.1), Corpus callosum, genu (white matter) (60.7), Dorsal funiculus (white matter) (59.6), Parieto-temporal junction (white matter) (58.2), Occipital cortex (white matter) (58.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4, SP1, TP53

miRNA regulators (miRDB)

Targeting DUT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 83 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Functional genomics

gnomAD constraint: pLI 3.39e-07, LOEUF 1.68, missense Z -1.21 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000331200 — one region, missense o/e 0.98. DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H209 (-3.266), NCO2 (-3.25), JHH-6 (-3.189), LOU-NH91 (-3.083), NCI-H3122 (-3.069), SNU-308 (-3.051), SNU-478 (-3.028), THP-1 (-3.011), SU-DHL-4 (-2.99), TE-5 (-2.988), PA-TU-8988S (-2.953), KE-37 (-2.934), OE33 (-2.912), LS1034 (-2.893), RD-ES (-2.8).

Literature-anchored findings (GeneRIF, showing 21)

• Novel gain of function activity of p53 mutants: activation of the dUTPase gene expression leading to resistance to 5-fluorouracil. (PMID:12096336)
• Nuclear dUTPase may contain a complex nuclear localization signal that is located throughout the entire protein. (PMID:12799180)
• dUTPase staining provides a useful measure of cell proliferation distinct from that offered by Ki-67 labeling. It proved particularly useful for the evaluation of diffuse astrocytomas. (PMID:16325515)
• kinetic model of the human dUTPase catalytic cycle (PMID:17848562)
• determined the crystal structure of the enzyme:alpha,beta-imino-dUTP (PMID:17880943)
• Establishment of a direct role for both mutant and wild-type forms of p53 in modulating dUTPase promoter activity. (PMID:19015155)
• hinge proline destabilize human and Escherichia coli dUTPases without preventing trimeric organization (PMID:19302784)
• significant differences between the human and Plasmodium dUTPases (PMID:19879316)
• nuclear dUTPase may be a good biomarker for predicting prognosis in HCC patients after surgical resection (PMID:19968781)
• High dUTP pyrophosphatase is associated with recurrence in colorectal cancer patients undergoing 5-fluorouracil adjuvant chemotherapy (PMID:20560137)
• Repression of dUTPase induced specific expression level increments for thymidylate kinase and thymidine kinase, and also an increased sensitization to 5-fluoro-2’-deoxyuridine and 5-fluoro-uracil. (PMID:21780905)
• Data sugget that inhibition of dUTPase is a mechanism-based therapeutic approach to significantly enhance the efficacy of thymidylate synthase (TS)-targeted chemotherapeutic agents. (PMID:22172489)
• EBV-encoded dUTPase may act as an intercellular signaling molecule capable of modulating the cellular microenvironment (PMID:23894549)
• Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus. (PMID:24311590)
• A single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene was associated with a syndrome of bone marrow failure and diabetes. (PMID:28073829)
• This study reports that the Staphylococcal repressor protein StlSaPIBov1 (Stl) forms strong complex with human dUTPase. (PMID:29531348)
• These findings suggested that the homozygous GG allele of rs3784619 and the TT allele of rs11637235 in the DUT gene significantly increased the risk of cervical intraepithelial neoplasia III and cervical squamous cell carcinomas. (PMID:30679536)
• Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability. (PMID:34584184)
• DUT enhances drug resistance to proteasome inhibitors via promoting mitochondrial function in multiple myeloma. (PMID:36426924)
• Discovery of two new isoforms of the human DUT gene. (PMID:37173337)
• Structural dynamics of human deoxyuridine 5’-triphosphate nucleotidohydrolase (dUTPase). (PMID:39477983)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000102748
danio_rerio	dut	ENSDARG00000106529
mus_musculus	Dut	ENSMUSG00000027203
rattus_norvegicus	Dut	ENSRNOG00000007221
drosophila_melanogaster	dUTPase	FBGN0250837
caenorhabditis_elegans	dut-1	WBGENE00010609

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1346051) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal inner cell mass morphology	1
abnormal trophectoderm morphology	1
embryonic lethality between implantation and placentation, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Candida albicans WO-1	C4YFC7	100.0%	Diamond
Candida albicans SC5314	P0CY19	100.0%	Diamond
Saccharomyces cerevisiae S288C	P33317	81.7%	Diamond
Nakaseomyces glabratus CBS 138	Q6FKQ6	81.7%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CQN7	81.6%	Diamond
Eremothecium gossypii ATCC 10895	Q74ZF0	81.0%	Diamond
Oryza sativa Japonica Group	Q10FF9	78.2%	Diamond
Solanum lycopersicum	P32518	77.3%	Diamond
Arabidopsis thaliana	Q9STG6	77.3%	Diamond
Debaryomyces hansenii CBS767	Q6BRN7	74.4%	Diamond
Dictyostelium discoideum	Q54BW5	73.2%	Diamond
Schizosaccharomyces pombe 972h-	Q9P6Q5	70.6%	Diamond
Neurospora crassa OR74A	Q6MVL2	68.4%	Diamond
Yarrowia lipolytica CLIB122	Q6C141	64.3%	Diamond
Methanothermobacter thermautotrophicus str. Delta H	O27642	48.7%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SRS0	45.0%	Diamond
Antonospora locustae	Q6E4Q0	43.3%	Diamond
Variola virus human/India/Ind3/1967	P0DSZ7	100.0%	Diamond
Variola virus	P0DSZ8	100.0%	Diamond
Vaccinia virus Copenhagen	P68634	100.0%	Diamond
Vaccinia virus L-IPV	P68635	100.0%	Diamond
Vaccinia virus Ankara	Q76RE7	100.0%	Diamond
Camelpox virus CMS	Q775Z7	100.0%	Diamond
Camelpox virus M-96	Q8V2Y0	100.0%	Diamond
Vaccinia virus WR	P17374	99.3%	Diamond
Rabbitpox virus Utrecht	Q6RZR1	99.3%	Diamond
Monkeypox virus	A0A7H0DN19	98.6%	Diamond
Cowpox virus (strain GRI-90)	P87630	98.6%	Diamond
Feline immunodeficiency virus (isolate Petaluma)	P16088	94.8%	Diamond
Feline immunodeficiency virus (isolate San Diego)	P19028	94.8%	Diamond
Feline immunodeficiency virus (isolate TM2)	P31822	86.2%	Diamond
Caprine arthritis encephalitis virus strain Cork	P33459	77.5%	Diamond
Orf virus (strain NZ2)	P14597	73.2%	Diamond
Fowl aviadenovirus 1	Q89662	69.5%	Diamond
Fowl aviadenovirus 8	Q9YYS0	69.5%	Diamond
Yaba monkey tumor virus strain VR587	Q6TUZ4	64.3%	Diamond
Frog virus 3 (isolate Goorha)	Q6GZR2	63.0%	Diamond
Swinepox virus (STRAIN KASZA)	P32208	62.9%	Diamond
Paramecium bursaria Chlorella virus 1	O41033	62.3%	Diamond
Fowlpox virus strain NVSL	Q9J5G5	61.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DUT-AS1	ncRNA	107984757
FBN1	protein-coding	2200
CEP152	protein-coding	22995
CTXN2-AS1	ncRNA	105370807
FBN1-DT	ncRNA	105370809
CTXN2	protein-coding	399697
SLC12A1	protein-coding	6557
SLC24A5	protein-coding	283652
MYEF2	protein-coding	50804

Protein

Protein identifiers

Deoxyuridine 5’-triphosphate nucleotidohydrolase, mitochondrial — P33316 (reviewed: P33316)

Alternative names: dUTP pyrophosphatase

All UniProt accessions (8): A0A0C4DGL3, H0YKC5, H0YKI0, H0YMM5, H0YMP1, H0YNJ9, H0YNW5, P33316

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the cleavage of 2’-deoxyuridine 5’-triphosphate (dUTP) into 2’-deoxyuridine 5’-monophosphate (dUMP) and inorganic pyrophosphate and through its action efficiently prevents uracil misincorporation into DNA and at the same time provides dUMP, the substrate for de novo thymidylate biosynthesis. Inhibits peroxisome proliferator-activated receptor (PPAR) activity by binding of its N-terminal to PPAR, preventing the latter’s dimerization with retinoid X receptor. Essential for embryonic development.

Subunit / interactions. Homotrimer.

Subcellular location. Nucleus Mitochondrion.

Tissue specificity. Found in a variety of tissues. Isoform 3 expression is constitutive, while isoform 2 expression correlates with the onset of DNA replication (at protein level). Isoform 2 degradation coincides with the cessation of nuclear DNA replication (at protein level).

Post-translational modifications. Nuclear isoform 2 is phosphorylated in vivo on Ser-11, a reaction that can be catalyzed in vitro by CDC2. Phosphorylation in mature T-cells occurs in a cell cycle-dependent manner. Isoform 3 is not phosphorylated.

Disease relevance. Bone marrow failure and diabetes mellitus syndrome (BMFDMS) [MIM:620044] A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFDMS is an autosomal recessive form characterized by various degrees of bone marrow failure, ranging from dyserythropoiesis to bone marrow aplasia, with onset in infancy or early childhood, and non-autoimmune insulin-dependent diabetes mellitus appearing in the first or second decades. Many patients show pigmentary skin abnormalities and short stature. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphorylation is necessary for activity.

Pathway. Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP route): step 2/2.

Miscellaneous. Each trimer binds three substrate molecules. The ligands are bound between subunits, and for each substrate molecule, residues from adjacent subunits contribute to the binding interactions. Major isoform.

Similarity. Belongs to the dUTPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P33316-3	3, DUT-M	yes
P33316-2	2, DUT-N

RefSeq proteins (4): NP_001020419, NP_001020420, NP_001317215, NP_001939 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008181	dUTPase	Family
IPR029054	dUTPase-like	Domain
IPR033704	dUTPase_trimeric	Domain
IPR036157	dUTPase-like_sf	Homologous_superfamily

Pfam: PF00692

Enzyme classification (BRENDA)

• EC 3.6.1.23 — dUTP diphosphatase (BRENDA: 71 organisms, 106 substrates, 269 inhibitors, 149 Km, 112 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DUTP	0.0001–3.788	107
DTTP	0.11–0.761	6
DCTP	0.077–2.3	5
DUDP	0.0062–0.17	5
UTP	0.035–1	4
2’-DEOXY-5-FLUORO-UTP	0.0017–0.0061	2
BETA-L-2’-DUTP	0.438–0.523	2
DATP	0.0094–1.13	2
DGTP	0.21–1.96	2
DITP	0.0447	1
DUTP-CO2+	0.0027	1
DUTP-MG2+	0.0019	1
DUTP-MN2+	0.0137	1
DUTPALPHAS	0.0002	1

Catalyzed reactions (Rhea)

• dUTP + H2O = dUMP + diphosphate + H(+) (RHEA:10248)

UniProt features (39 total): strand 14, binding site 5, sequence variant 4, helix 4, modified residue 3, sequence conflict 2, transit peptide 1, chain 1, splice variant 1, mutagenesis site 1, region of interest 1, turn 1, initiator methionine 1

Structure

Experimental structures (PDB)

12 structures by resolution:

PDB	Title	Method	Resolution (Å)
3ARA	Discovery of Novel Uracil Derivatives as Potent Human dUTPase Inhibitors	X-RAY DIFFRACTION	1.7
3ARN	Human dUTPase in complex with novel uracil derivative	X-RAY DIFFRACTION	1.8
3EHW	Human dUTPase in complex with alpha,beta-imido-dUTP and Mg2+: visualization of the …	X-RAY DIFFRACTION	1.8
5H4J	Crystal structure of Human dUTPase in complex with …	X-RAY DIFFRACTION	1.8
4MZ6	Structure of importin-alpha: dUTPase S11E NLS mutant complex	X-RAY DIFFRACTION	1.88
7PWJ	dUTPase from human in complex with Stl	X-RAY DIFFRACTION	1.94
1Q5H	Human dUTP Pyrophosphatase complex with dUDP	X-RAY DIFFRACTION	2
1Q5U	HUMAN DUTP PYROPHOSPHATASE	X-RAY DIFFRACTION	2
24OK	Crystal structure of human dUTPase complexed with Zinc.	X-RAY DIFFRACTION	2.01
4MZ5	Structure of importin-alpha: dUTPase NLS complex	X-RAY DIFFRACTION	2.1
2HQU	Human dUTPase in complex with alpha,beta-iminodUTP and magnesium ion	X-RAY DIFFRACTION	2.2
8C8I	Human dUTPase in complex with a potent proteinaceous inhibitor (Stl)	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33316-F1	75.51	0.53

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH enhanced · IF supported

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 (5)

Position	Role
173–175	dUTP
187–193	dUTP
198	dUTP
241	dUTP
246–247	dUTP

Post-translational modifications (3)

Type	Positions
Phosphoserine	11, 88, 99

Mutagenesis-validated functional residues (1)

Position	Phenotype
99	loss of phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 1; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

1 pathways:

ID	Pathway	Evidence
R-HSA-499943	Interconversion of nucleotide di- and triphosphates	curated

MSigDB gene sets: 365 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, MORF_DNMT1, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, CROONQUIST_NRAS_SIGNALING_DN, GCM_NPM1, MORF_RRM1, MORF_HDAC1, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_HDAC2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GNF2_MCM5, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (10): liver development (GO:0001889), nucleobase-containing compound metabolic process (GO:0006139), dUMP biosynthetic process (GO:0006226), dTMP biosynthetic process (GO:0006231), DNA replication (GO:0006260), regulation of protein-containing complex assembly (GO:0043254), dUTP catabolic process (GO:0046081), nucleotide metabolic process (GO:0009117), pyrimidine deoxyribonucleoside monophosphate biosynthetic process (GO:0009177), pyrimidine deoxyribonucleotide biosynthetic process (GO:0009221)

GO Molecular Function (10): magnesium ion binding (GO:0000287), RNA binding (GO:0003723), dUTP diphosphatase activity (GO:0004170), signaling receptor inhibitor activity (GO:0030547), pyrimidine deoxyribonucleotide binding (GO:0032556), identical protein binding (GO:0042802), peroxisome proliferator activated receptor binding (GO:0042975), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), extracellular exosome (GO:0070062)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Metabolism of nucleotides	1

GO top-level categories

41 GO namespaces:

Category	Terms
pyrimidine deoxyribonucleoside monophosphate biosynthetic process	2
pyrimidine deoxyribonucleotide biosynthetic process	2
intracellular membrane-bounded organelle	2
gland development	1
hepaticobiliary system development	1
primary metabolic process	1
dUMP metabolic process	1
dTMP metabolic process	1
DNA metabolic process	1
DNA biosynthetic process	1
regulation of cellular component biogenesis	1
regulation of cellular component organization	1
protein-containing complex assembly	1
deoxyribonucleoside triphosphate catabolic process	1
pyrimidine deoxyribonucleoside triphosphate catabolic process	1
pyrimidine deoxyribonucleotide catabolic process	1
dUTP metabolic process	1
nucleoside phosphate metabolic process	1
pyrimidine nucleoside monophosphate biosynthetic process	1
deoxyribonucleoside monophosphate biosynthetic process	1
pyrimidine deoxyribonucleoside monophosphate metabolic process	1
pyrimidine nucleotide biosynthetic process	1
pyrimidine deoxyribonucleotide metabolic process	1
2’-deoxyribonucleotide biosynthetic process	1
metal ion binding	1
nucleic acid binding	1
nucleoside triphosphate diphosphatase activity	1
signaling receptor regulator activity	1
signaling receptor activity	1
molecular function inhibitor activity	1
pyrimidine nucleotide binding	1
carbohydrate derivative binding	1
protein binding	1
signaling receptor binding	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
dTMP biosynthetic process	BP	direct assay
extracellular exosome	CC	high-throughput assay
mitochondrion	CC	high-throughput
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay
dUTP diphosphatase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,872 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUT	UNG	P13051	766
DUT	MYOM2	P54296	719
DUT	DTYMK	P23919	714
DUT	DCTD	P32321	686
DUT	TYMS	P04818	676
DUT	PPARA	Q07869	651
DUT	RRM1	P23921	525
DUT	UMPS	P11172	523
DUT	TK2	O00142	521
DUT	TK1	P04183	497
DUT	CDA	P32320	486
DUT	IL6	P05231	463
DUT	UPP1	Q16831	456
DUT	CAD	P27708	455
DUT	DHFR	P00374	452

IntAct

Human interaction partners of DUT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
NUDT18	physical association	0.620	3
PLEKHF2	physical association	0.490	2
STAT3	physical association	0.400	1
TLN1	physical association	0.400	1
RHOB	physical association	0.370	1
SPATA2	physical association	0.370	1
GH1	physical association	0.000	1
PINX1	physical association	0.000	1

BioGRID (154 interactions; top human partners by supporting records): MYC (Affinity Capture-MS; 2 records), NUDT18 (Two-hybrid; 2 records), PARK2 (Proximity Label-MS; 2 records), AAR2 (Affinity Capture-MS), ABCE1 (Affinity Capture-MS), AK2 (Co-fractionation), ALDOA (Co-fractionation), ALDOC (Co-fractionation), ARHGAP11B (Affinity Capture-MS), ARHGAP35 (Affinity Capture-MS), ARHGDIA (Co-fractionation), ASXL1 (Affinity Capture-MS), ASXL2 (Affinity Capture-MS), ASXL3 (Affinity Capture-MS), BCAS2 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for DUT: 28 ClinVar records (3 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	15
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1706580	NM_001025248.2(DUT):c.425A>G (p.Tyr142Cys)	Likely pathogenic	criteria provided, single submitter	2
666430	Single allele	Pathogenic	criteria provided, single submitter	1
4851052	GRCh37/hg19 15q21.1(chr15:48532679-48631634)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore DUT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 786):

Position(s)	Effect	Δscore	Sites
15:48341287–48341288	acceptor_loss	1.0000	4
15:48341364–48341365	donor_loss	1.0000	5
15:48341513	acceptor_gain	1.0000
15:48331750	donor_gain	0.9900
15:48331775	donor_gain	0.9900
15:48332219–48332220	acceptor_gain	0.9900	2
15:48332407–48332408	donor_loss	0.9900	5
15:48336044–48336045	acceptor_loss	0.9900	4
15:48336091–48336092	donor_loss	0.9900	6
15:48341287–48341288	acceptor_loss	0.9900	2

AlphaMissense

557 missense substitutions predicted likely pathogenic (of 1,597 scored), across 123 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D190	8	0.993	0.996
D137	8	0.987	0.995
D192	8	0.986	0.997
F246	8	0.938	0.998
D157	8	0.936	0.989
F202	8	0.911	0.990
D183	8	0.865	0.931
D215	8	0.808	0.941
R241	7	0.962	0.992
N203	7	0.953	0.998
Q219	7	0.949	0.996
C222	7	0.945	0.995
F209	7	0.919	0.988
E223	7	0.917	0.986
F116	7	0.906	0.994
F204	7	0.900	0.962
S140	7	0.897	0.996
C166	7	0.788	0.975
R169	6	0.966	0.992
G135	6	0.959	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000382
Lung Adenocarcinoma (TCGA)	unfavorable	0.000715

Disease associations

OMIM: gene MIM:601266 | disease phenotypes: MIM:620044, MIM:154700

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
bone marrow failure and diabetes mellitus syndrome	Strong	Autosomal recessive	2

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Cytopenia - NOT Fanconi anaemia	green
Monogenic diabetes	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (2): bone marrow failure and diabetes mellitus syndrome (MONDO:0859288), Marfan syndrome (MONDO:0007947)

Orphanet (2): Marfan syndrome type 1 (Orphanet:284963), Marfan syndrome (Orphanet:558)

HPO phenotypes

11 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001876	Pancytopenia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0003764	Nevus
HP:0005518	Increased mean corpuscular volume
HP:0006727	T-cell acute lymphoblastic leukemias
HP:0025329	Anti-glutamic acid decarboxylase antibody positivity
HP:0034063	Anti-islet antigen-2 antibody positivity
HP:0100651	Type I diabetes mellitus

GWAS associations

4 associations:

Study	Trait	p-value
GCST008839_2	Height	4e-23
GCST004219_4	Skin pigmentation	3e-14
GCST006585_895	Blood protein levels	2e-11
GCST000189_46	Protein quantitative trait loci	3e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004502	adiponectin measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D008382	Marfan Syndrome	C05.116.099.674; C14.240.400.725; C14.280.400.725; C16.131.077.550; C16.131.240.400.720; C16.320.540; C17.300.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5203 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

114 measured of 282 human assays (382 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	21 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]propyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	30 nM	US-8883759: Anti-tumor effect potentiator
N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	40 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
N-[(1R)-1-(3-cyclopentyloxy-4-fluorophenyl)ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	40 nM	US-8883759: Anti-tumor effect potentiator
CHEMBL2147981	EC50	49 nM
CHEMBL2163854	EC50	50 nM
CHEMBL2163852	IC50	58 nM
N-[(1R)-1-(3-cyclopentyloxyphenyl)ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	60 nM	US-8883759: Anti-tumor effect potentiator
(E)-N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]ethyl]-5-(2,4-dioxopyrimidin-1-yl)pent-3-ene-1-sulfonamide	EC50	66 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2163866	EC50	70 nM
CHEMBL2147979	EC50	71 nM
CHEMBL2147987	EC50	96 nM
CHEMBL2147977	EC50	100 nM
CHEMBL2147976	EC50	120 nM
3-(cyclopropylmethoxy)-N-[2-[4-[(2,4-dioxopyrimidin-1-yl)methyl]phenyl]propan-2-yl]benzenesulfonamide	EC50	140 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
(E)-N-[(1R)-1-(3-cyclopentyloxyphenyl)ethyl]-5-(2,4-dioxopyrimidin-1-yl)pent-3-ene-1-sulfonamide	EC50	150 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2048477	IC50	150 nM
CHEMBL2163863	IC50	150 nM
CHEMBL2163856	IC50	150 nM
CHEMBL2163865	IC50	170 nM
CHEMBL2147980	EC50	200 nM
CHEMBL2163857	IC50	210 nM
CHEMBL2048476	IC50	230 nM
CHEMBL2163851	EC50	260 nM
CHEMBL2048480	IC50	280 nM
CHEMBL2046464	IC50	290 nM
CHEMBL2048443	KI	300 nM
CHEMBL2048481	IC50	310 nM
CHEMBL1234349	IC50	320 nM
3-(cyclopropylmethoxy)-N-[1-[3-(2,4-dioxopyrimidin-1-yl)propoxy]-2-methylpropan-2-yl]benzenesulfonamide	IC50	330 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
N-[2-[3-(cyclopropylmethoxy)phenyl]propan-2-yl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	340 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2048469	IC50	350 nM
CHEMBL2163867	IC50	350 nM
CHEMBL2163861	IC50	360 nM
1-[3-[2-[bis(3-fluorophenyl)-hydroxymethyl]pyrrolidin-1-yl]sulfonylpropyl]pyrimidine-2,4-dione	IC50	380 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2163877	IC50	390 nM
1-[3-[2-[bis(4-fluorophenyl)-hydroxymethyl]pyrrolidin-1-yl]sulfonylpropyl]pyrimidine-2,4-dione	IC50	400 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2147978	EC50	450 nM
1-[3-[2-[hydroxy(diphenyl)methyl]pyrrolidin-1-yl]sulfonylpropyl]pyrimidine-2,4-dione	IC50	480 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2163860	IC50	550 nM
CHEMBL2048471	IC50	580 nM
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]propyl]-4-[(2,4-dioxopyrimidin-1-yl)methyl]benzenesulfonamide	IC50	580 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2048470	IC50	600 nM
N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]propyl]-3-(2,4-dioxo-1,3-diazinan-1-yl)propane-1-sulfonamide	IC50	610 nM	US-8883759: Anti-tumor effect potentiator
CHEMBL2147983	EC50	610 nM
CHEMBL2147984	EC50	610 nM
CHEMBL2163859	IC50	630 nM
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]ethyl]-3-(2,4-dioxopyrimidin-1-yl)propane-1-sulfonamide	IC50	660 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
CHEMBL2163855	IC50	720 nM
CHEMBL2163869	IC50	740 nM

ChEMBL bioactivities

275 potent at pChembl≥5 of 310 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.68	IC50	21	nM	CHEMBL2057911
7.58	IC50	26	nM	CHEMBL2147981
7.55	IC50	28	nM	CHEMBL2147979
7.54	IC50	29	nM	CHEMBL2163854
7.52	IC50	30	nM	CHEMBL3664406
7.52	IC50	30	nM	CHEMBL3664416
7.52	IC50	30	nM	CHEMBL3664420
7.51	IC50	31	nM	CHEMBL2147976
7.48	IC50	33	nM	CHEMBL2147980
7.46	IC50	35	nM	CHEMBL2057599
7.43	Kd	37.07	nM	CHEMBL5653589
7.43	ED50	37.07	nM	CHEMBL5653589
7.41	IC50	39	nM	CHEMBL2147985
7.40	IC50	40	nM	CHEMBL2057909
7.40	IC50	40	nM	CHEMBL3659896
7.40	IC50	40	nM	CHEMBL3664407
7.40	IC50	40	nM	CHEMBL3664409
7.40	IC50	40	nM	CHEMBL3664423
7.40	IC50	40	nM	CHEMBL3664464
7.40	IC50	40	nM	CHEMBL3664511
7.39	IC50	41	nM	CHEMBL2147986
7.31	EC50	49	nM	CHEMBL2147981
7.30	EC50	50	nM	CHEMBL2163854
7.30	IC50	50	nM	CHEMBL2057909
7.30	IC50	50	nM	CHEMBL2147985
7.24	IC50	58	nM	CHEMBL2163852
7.22	IC50	60	nM	CHEMBL3659894
7.21	IC50	62	nM	CHEMBL2057601
7.18	EC50	66	nM	CHEMBL2147985
7.17	IC50	67	nM	CHEMBL2163866
7.16	EC50	70	nM	CHEMBL2163866
7.16	IC50	70	nM	CHEMBL3664465
7.15	EC50	71	nM	CHEMBL2147979
7.14	IC50	73	nM	CHEMBL2147975
7.14	IC50	73	nM	CHEMBL2147977
7.09	IC50	82	nM	CHEMBL2147987
7.05	IC50	90	nM	CHEMBL2057911
7.05	IC50	90	nM	CHEMBL3664425
7.02	EC50	96	nM	CHEMBL2147987
7.00	EC50	100	nM	CHEMBL2147977
7.00	IC50	100	nM	CHEMBL3664408
7.00	IC50	100	nM	CHEMBL3664419
7.00	IC50	100	nM	CHEMBL3664422
6.96	IC50	110	nM	CHEMBL3664449
6.96	IC50	110	nM	CHEMBL3664500
6.92	EC50	120	nM	CHEMBL2147976
6.92	IC50	120	nM	CHEMBL3664469
6.92	IC50	120	nM	CHEMBL3664472
6.89	IC50	130	nM	CHEMBL3664499
6.85	EC50	140	nM	CHEMBL2147975

PubChem BioAssay actives

100 with measured affinity, of 302 total; 50 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
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	671720: Inhibition of human dUTPase assessed as production of [5-3H]dUMP from [5-3H]dUTP after 15 mins measured by HPLC analysis	ic50	0.0210	uM
3-(2,2-difluoroethoxy)-N-[(E)-7-(2,4-dioxopyrimidin-1-yl)-2-methylhept-5-en-2-yl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0260	uM
3-(cyclopropylmethoxy)-N-[(E)-7-(2,4-dioxopyrimidin-1-yl)-2-methylhept-5-en-2-yl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0280	uM
1-[4-[3-[(2R)-2-[3-(cyclopropylmethoxy)phenyl]butyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.0290	uM
3-cyclopentyloxy-N-[2-[4-[(2,4-dioxopyrimidin-1-yl)methyl]phenyl]propan-2-yl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0310	uM
3-cyclopentyloxy-N-[(E)-7-(2,4-dioxopyrimidin-1-yl)-2-methylhept-5-en-2-yl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0330	uM
3-(cyclopropylmethoxy)-N-[5-[(2,4-dioxopyrimidin-1-yl)methoxy]-2-methylpentan-2-yl]benzenesulfonamide	671720: Inhibition of human dUTPase assessed as production of [5-3H]dUMP from [5-3H]dUTP after 15 mins measured by HPLC analysis	ic50	0.0350	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148269: Binding affinity to human DUT incubated for 45 mins by Kinobead based pull down assay	kd	0.0371	uM
(E)-N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]ethyl]-5-(2,4-dioxopyrimidin-1-yl)pent-3-ene-1-sulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0390	uM
N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	671720: Inhibition of human dUTPase assessed as production of [5-3H]dUMP from [5-3H]dUTP after 15 mins measured by HPLC analysis	ic50	0.0400	uM
(E)-N-[(1R)-1-(3-cyclopentyloxyphenyl)ethyl]-5-(2,4-dioxopyrimidin-1-yl)pent-3-ene-1-sulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0410	uM
1-[4-[3-[(2R)-2-[3-(cyclopropylmethoxy)phenyl]propyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.0580	uM
N-[1-[3-(cyclopropylmethoxy)phenyl]ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	671720: Inhibition of human dUTPase assessed as production of [5-3H]dUMP from [5-3H]dUTP after 15 mins measured by HPLC analysis	ic50	0.0620	uM
1-[4-[3-[(2S)-2-[3-(cyclopropylmethoxy)-4-fluorophenyl]-2-hydroxybutyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.0670	uM
3-(cyclopropylmethoxy)-N-[2-[4-[(2,4-dioxopyrimidin-1-yl)methyl]phenyl]propan-2-yl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0730	uM
3-(2,2-difluoroethoxy)-N-[2-[4-[(2,4-dioxopyrimidin-1-yl)methyl]phenyl]propan-2-yl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0730	uM
(E)-N-[(1R)-1-[3-(2,2-difluoroethoxy)phenyl]ethyl]-5-(2,4-dioxopyrimidin-1-yl)pent-3-ene-1-sulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.0820	uM
1-[4-[(2S)-2-benzhydrylpyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.1500	uM
1-[4-[3-[(2S)-2-[3-(cyclopropylmethoxy)phenyl]-2-hydroxybutyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.1500	uM
1-[4-[3-[(2S)-2-[3-(cyclobutylmethoxy)phenyl]-2-hydroxybutyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.1500	uM
1-[2-[3-[(2S)-2-[3-(cyclopropylmethoxy)phenyl]-2-hydroxybutyl]triazol-4-yl]ethoxymethyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.1700	uM
1-[4-[3-[2-[3-(cyclopropylmethoxy)phenyl]ethyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.2100	uM
1-[4-[3-[(2S)-2-(3-cyclopentyloxyphenyl)-2-hydroxybutyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.2100	uM
1-[4-[(2S)-2-[hydroxy-bis(3-thiophen-3-ylphenyl)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.2300	uM
1-[3-[(2R)-2-[bis(3-fluorophenyl)-hydroxymethyl]pyrrolidin-1-yl]sulfonylpropyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.2800	uM
1-[4-[(2S)-2-[hydroxy(diphenyl)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.2900	uM
[(2R,3S,5R)-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-[[hydroxy-[hydroxy(phenylmethoxy)phosphoryl]oxyphosphoryl]methyl]phosphinic acid	669111: Inhibition of human dUTPase	ki	0.3000	uM
1-[3-[(2R)-2-[bis(4-fluorophenyl)-hydroxymethyl]pyrrolidin-1-yl]sulfonylpropyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.3100	uM
1-[3-[(2R)-2-[hydroxy(diphenyl)methyl]pyrrolidin-1-yl]sulfonylpropyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.3200	uM
N-[2-[3-(cyclopropylmethoxy)phenyl]propan-2-yl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	671720: Inhibition of human dUTPase assessed as production of [5-3H]dUMP from [5-3H]dUTP after 15 mins measured by HPLC analysis	ic50	0.3400	uM
N-[(E)-7-(2,4-dioxopyrimidin-1-yl)-2-methylhept-5-en-2-yl]-3-methoxybenzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.3400	uM
1-[4-[(2S)-2-[bis(3-fluorophenyl)-hydroxymethyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.3500	uM
1-[4-[3-[(2R)-2-[3-(cyclopropylmethoxy)-4-fluorophenyl]-2-hydroxybutyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.3500	uM
1-[4-[3-[(2S)-2-hydroxy-2-(3-prop-2-enoxyphenyl)butyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.3600	uM
1-[4-[3-[2-[2-(cyclopropylmethoxy)phenyl]ethyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.3900	uM
N-[(1R)-1-[3-(2,2-difluoroethoxy)phenyl]ethyl]-4-[(2,4-dioxopyrimidin-1-yl)methyl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.4100	uM
N-[(1R)-1-(3-cyclopentyloxyphenyl)ethyl]-4-[(2,4-dioxopyrimidin-1-yl)methyl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.4300	uM
1-[4-[3-[(2S)-2-hydroxy-2-[3-(2-methylpropoxy)phenyl]butyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.5500	uM
1-[4-[(2S)-2-[bis(3-chlorophenyl)-hydroxymethyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.5800	uM
1-[4-[(2S)-2-[bis(4-fluorophenyl)-hydroxymethyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4-dione	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	0.6000	uM
1-[4-[3-[(2S)-2-hydroxy-2-[3-[(1-methylcyclopropyl)methoxy]phenyl]butyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.6300	uM
1-[4-[3-[(2S)-2-[3-(cyclopropylmethoxy)phenyl]butyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.7200	uM
1-[4-[3-(2,2-diphenylethyl)triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.7400	uM
N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]ethyl]-4-[(2,4-dioxopyrimidin-1-yl)methyl]benzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	0.8200	uM
1-[4-[3-[(2S)-2-[3-(cyclopropylmethoxy)phenyl]propyl]triazol-4-yl]butyl]pyrimidine-2,4-dione	698315: Inhibition of human dUTPase assessed as reduction in [5-3H]dUMP production incubated for 15 mins by HPLC	ic50	0.8700	uM
4-(2,4-dioxopyrimidin-1-yl)-N-(2-hydroxy-2,2-diphenylethyl)-N-methylbutanamide	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	1.1000	uM
1-[3-[3-(2,2-diphenylethyl)triazol-4-yl]propyl]pyrimidine-2,4-dione	698318: Inhibition of dUTPase in human HeLa S3 cells assessed as potentiation of 1 uM FdUrd-induced decrease in cell density incubated for 48 hrs by crystal violet assay	ec50	1.1000	uM
N-[5-[(2,4-dioxopyrimidin-1-yl)methoxy]-2-methylpentan-2-yl]-3-methoxybenzenesulfonamide	671720: Inhibition of human dUTPase assessed as production of [5-3H]dUMP from [5-3H]dUTP after 15 mins measured by HPLC analysis	ic50	1.2000	uM
N-[2-[4-[(2,4-dioxopyrimidin-1-yl)methyl]phenyl]propan-2-yl]-3-methoxybenzenesulfonamide	687171: Inhibition of human dUTPase-mediated formation of [5-3H]dUMP expressed in Escherichia coli BL21 (DE3) after 15 mins by HPLC analysis	ic50	1.2700	uM
4-(2,4-dioxopyrimidin-1-yl)-N-(2,2-diphenylethyl)-N-methylbutanamide	669109: Inhibition of human dUTPase using [5-3H]dUTP as substrate after 15 mins by HPLC analysis	ic50	1.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
sodium arsenite	decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
cobaltous chloride	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Carbamazepine	affects expression	2
Fluorouracil	decreases response to substance, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
bufalin	decreases expression	1
perfluorooctanoic acid	increases expression	1
periodate-oxidized adenosine	affects expression	1
gossypol acetic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
beta-hydroxyisovalerylshikonin	decreases activity, decreases phosphorylation, decreases reaction	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	decreases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1767581	Binding	Inhibition of human dUTPase by spectrophotometric analysis	β-Branched acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase. — *Bioorg Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

58 trials:

NCT	Phase	Status	Title
NCT01295047	Phase 4	COMPLETED	Comparison of Medical Therapies in Marfan Syndrome.
NCT00429364	Phase 3	COMPLETED	Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome
NCT00485368	Phase 3	COMPLETED	Angiotensin Converting Enzyme Inhibitors in Marfan Syndrome
NCT00683124	Phase 3	UNKNOWN	Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients
NCT00723801	Phase 3	COMPLETED	Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
NCT00763893	Phase 3	TERMINATED	Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
NCT00782327	Phase 3	COMPLETED	Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
NCT01145612	Phase 3	UNKNOWN	Atenolol Versus Losartan in the Prevention of Progressive Dilation of the Aorta in Marfan Syndrome
NCT01361087	Phase 3	WITHDRAWN	Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome
NCT01715207	Phase 3	COMPLETED	Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS
NCT00593710	Phase 2	COMPLETED	Losartan Versus Atenolol for the Treatment of Marfan Syndrome
NCT00651235	Phase 2	UNKNOWN	A Randomized, Open-label, LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome
NCT01949233	Phase 2	UNKNOWN	The Oxford Marfan Trial
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00270686	Not specified	COMPLETED	Studies of Heritable Disorders of Connective Tissue
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT01707563	Not specified	COMPLETED	Clinical Variability in Marfan Syndrome
NCT01760668	Not specified	COMPLETED	Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome
NCT02050113	Not specified	RECRUITING	Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices
NCT02111668	Not specified	COMPLETED	Thoracic Aortic Dilatation Syndromes
NCT02148900	Not specified	UNKNOWN	Development of a Blood Test for Marfan Syndrome
NCT02213484	Not specified	COMPLETED	Micro RNAs as a Marker of Aortic Aneurysm in Hereditary Aortopathy Syndromes
NCT02815072	Not specified	UNKNOWN	Generation of Marfan Syndrome and Fontan Cardiovascular Models Using Patient-specific Induced Pluripotent Stem Cells
NCT03236571	Not specified	COMPLETED	Cardiorespiratory and Muscular Rehabilitation of Children and Young Adults With Marfan Syndrome.
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT03567460	Not specified	COMPLETED	Children and Adolescents With Marfan Syndrome: 10,000 Healthy Steps and Beyond
NCT03581682	Not specified	COMPLETED	Tele-Clinic Visits in Pediatric Marfan Patients Using Parental Echo: The Future?
NCT04194619	Not specified	RECRUITING	Pregnancy in Women With Rare Multisystemic Vascular Diseases: COGRare5 Study
NCT04319107	Not specified	COMPLETED	Classifying Ectopia Lentis in Marfan Syndrome Into Five Grades of Increasing Severity
NCT04553094	Not specified	COMPLETED	Effects of Personalized Training at Home Combining Endurance and Resistance in Patients Suffering From Marfan Syndrome
NCT04641325	Not specified	COMPLETED	Marfan Syndrome Moderate Exercise Pilot
NCT04731493	Not specified	UNKNOWN	Effect on the Quality of Life of a Therapeutic Education Program in Patients With Marfan Syndrome
NCT04774172	Not specified	COMPLETED	Mortality and Morbidity Outcomes in Marfans
NCT04776668	Not specified	COMPLETED	Living With Marfan Syndrome and Your Aorta
NCT04776681	Not specified	COMPLETED	Living With Marfans and Your Aorta: Surgical Outcomes Study
NCT04970459	Not specified	RECRUITING	Biological Collection for Marfan and Related Syndromes
NCT05123339	Not specified	COMPLETED	Clinical Signs and Activity Limitations Associated With Dural Ectasia in Patients With Marfan Disease
NCT05389865	Not specified	UNKNOWN	Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
NCT05516043	Not specified	COMPLETED	Safety and Performance of POLYTHESE® Vascular Prosthesis
NCT05578469	Not specified	UNKNOWN	Surgical Treatment of Marfan Syndrome With Subluxation Lens
NCT05700175	Not specified	ACTIVE_NOT_RECRUITING	Transcriptomic Study of Adult Population With Marfan Syndrome
NCT05702476	Not specified	RECRUITING	Marfan Syndrome (MFS) and Facial Dysmorphism: Non-invasive 3D Assessment
NCT05711693	Not specified	COMPLETED	Measurement of Heart-carotid Pulse Wave Velocity (hcPWV) by Laser Doppler Vibrometry (LDV)
NCT05712577	Not specified	UNKNOWN	Psychological Support in Adult Patients With Marfan Syndrome
NCT05720923	Not specified	ACTIVE_NOT_RECRUITING	Analysis of Muscular Properties in Patients With MFS and EDS
NCT05809323	Not specified	RECRUITING	Marfan Syndrome Moderate Exercise Trial II
NCT05838235	Not specified	RECRUITING	Adapted Physical Activity Program (APA) for Effort Rehabilitation of Children and Teenagers With Marfan Syndrome
NCT05944614	Not specified	COMPLETED	Towards Optimal Treatment of Marfan Syndrome
NCT05980104	Not specified	COMPLETED	Single-Session Empowered Relief Class for Marfan Syndrome and Related Conditions
NCT06257004	Not specified	UNKNOWN	Genome-wide Epistasis for Cardiovascular Severity in Marfan Study
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT06786754	Not specified	ENROLLING_BY_INVITATION	Fibroblasts and Thoracic Aortic Aneurysms: in Vitro Characterization in With Marfan Syndrome and Genetic Aortic Diseases
NCT06872268	Not specified	COMPLETED	APPLICATION OF THERAPEUTIC PHOTOGRAPHY AND EXPRESSIVE WRITING IN THE MANAGEMENT OF PATIENTS WITH MARFAN SYNDROME
NCT07169669	Not specified	NOT_YET_RECRUITING	Multicentre Longitudinal Study of Bone Mineralisation Characteristics in Marfan Syndrome and Ehlers-Danlos Syndrome
NCT07360704	Not specified	COMPLETED	Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes
NCT07419386	Not specified	NOT_YET_RECRUITING	Clinical and Psychosocial Factors Associated With Physical Activity Level in Adults With Marfan Syndrome
NCT07495267	Not specified	NOT_YET_RECRUITING	Nutritional Ketosis Marfan
NCT07672210	Not specified	RECRUITING	PregnAncy-Related Aortic DISsEction in China

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DUT across ~30M SureChEMBL compounds — explore on Sugi Predict.