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): 24 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_001025248

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: 13 — 10 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000331200, ENST00000455976, ENST00000558367, ENST00000558472, ENST00000558813, ENST00000558978, ENST00000559416, ENST00000559540, ENST00000559852, ENST00000559935, ENST00000561350, ENST00000915906, ENST00000949573

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
ENSE00001030201	48342022	48343373
ENSE00001487133	48331429	48331795
ENSE00003541445	48332268	48332406
ENSE00003603862	48336046	48336090
ENSE00003667790	48341515	48341585

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.

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

295 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

83 targeting DUT, 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-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

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

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

Protein

Protein identifiers

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

Alternative names: dUTP pyrophosphatase

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

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), 1 shown:

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

UniProt features (36 total): strand 14, binding site 5, sequence variant 4, modified residue 3, sequence conflict 2, transit peptide 1, chain 1, splice variant 1, mutagenesis site 1, region of interest 1, helix 1, turn 1, initiator methionine 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
3ARA	X-RAY DIFFRACTION	1.7
3ARN	X-RAY DIFFRACTION	1.8
3EHW	X-RAY DIFFRACTION	1.8
5H4J	X-RAY DIFFRACTION	1.8
4MZ6	X-RAY DIFFRACTION	1.88
7PWJ	X-RAY DIFFRACTION	1.94
1Q5H	X-RAY DIFFRACTION	2
1Q5U	X-RAY DIFFRACTION	2
24OK	X-RAY DIFFRACTION	2.01
4MZ5	X-RAY DIFFRACTION	2.1
2HQU	X-RAY DIFFRACTION	2.2
8C8I	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33316-F1	75.51	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 (5): 173–175; 187–193; 198; 241; 246–247

Post-translational modifications (3): 11, 88, 99

Mutagenesis-validated functional residues (1):

Position	Phenotype
99	loss of phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

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

Rollup of top-1 pathways:

Category	Pathways
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUT	PPARA	Q07869	777
DUT	MYOM2	P54296	766
DUT	UNG	P13051	735
DUT	TYMS	P04818	715
DUT	DTYMK	P23919	709
DUT	DCTD	P32321	695
DUT	NTHL1	P78549	614
DUT	TK1	P04183	576
DUT	RRM1	P23921	564
DUT	UMPS	P11172	544
DUT	TK2	O00142	519
DUT	CDA	P32320	512
DUT	NUDT5	Q9UKK9	490
DUT	UPP1	Q16831	485
DUT	TYMP	P19971	484

IntAct

55 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
NUDT18	DUT	psi-mi:“MI:0915”(physical association)	0.620
DUT	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
PLEKHF2	DUT	psi-mi:“MI:0915”(physical association)	0.490
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
STAT3	DUT	psi-mi:“MI:0915”(physical association)	0.400
DUT	TLN1	psi-mi:“MI:0915”(physical association)	0.400
DUT	RHOB	psi-mi:“MI:0915”(physical association)	0.370
DUT	SPATA2	psi-mi:“MI:0915”(physical association)	0.370
ORF69	PEPD	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
GRN	OPA1	psi-mi:“MI:0914”(association)	0.350
ARHGAP35	CSTB	psi-mi:“MI:0914”(association)	0.350
SOS2	SAP18	psi-mi:“MI:0914”(association)	0.350
ARHGAP11B	RPN1	psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
GRB2	MYO1C	psi-mi:“MI:0914”(association)	0.350
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
LETM2	EIF3CL	psi-mi:“MI:0914”(association)	0.350
HRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
KDM4A	TP53	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
HSPD1	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (150): DUT (Affinity Capture-MS), SPATA2 (Two-hybrid), NUDT18 (Two-hybrid), ARHGDIA (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation), DUT (Co-fractionation)

ESM2 similar proteins: A2BK57, A2SQW1, A4FW98, A6UQ71, A6UWW5, A6VH12, A9A9N7, O02607, O36404, P03195, P09254, P0A3V2, P0A3V3, P0A9K1, P0A9K2, P0C8H0, P0C8H2, P0C8H3, P0C9C3, P0C9C4, P0C9C5, P10234, P28892, P28893, P33316, P70583, P89079, P89469, Q00030, Q01034, Q07275, Q2FQM7, Q2HR78, Q3KST7, Q4JQW7, Q65143, Q65199, Q65243, Q66656, Q6FYR2

Diamond homologs: A0A7H0DN19, A0PT52, A0Q1N5, A0QW08, A1KM35, A1T7Y0, A1UF27, A3PYI9, A4QER2, A4TCR4, A5U649, A6TLM6, A7H9F9, A7HZC0, B0C9N7, B0K9P1, B0S1D8, B0TAH2, B1WN93, B2HM03, B2IKJ9, B3EPL0, B3QML1, B4S912, B4UHG6, B5EI65, B7KFZ3, B8ET39, B8FQZ6, B8JFZ2, B9L823, C0ZYU5, C1AFF6, C4YFC7, C6E2P3, O30931, O41033, O68992, P0A553, P0CY19

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
insulin receptor signaling pathway	5	21.7×	1e-03
Ras protein signal transduction	5	20.1×	1e-03
positive regulation of angiogenesis	5	11.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
666430	Single allele	Pathogenic
1706580	NM_001025248.2(DUT):c.425A>G (p.Tyr142Cys)	Likely pathogenic

SpliceAI

1014 predictions. Top by Δscore:

Variant	Effect	Δscore
15:48332404:CAGGT:C	donor_loss	1.0000
15:48332407:GT:G	donor_loss	1.0000
15:48332408:T:A	donor_loss	1.0000
15:48336044:A:AG	acceptor_gain	1.0000
15:48336045:G:GG	acceptor_gain	1.0000
15:48341287:A:AG	acceptor_gain	1.0000
15:48341287:AGCT:A	acceptor_gain	1.0000
15:48341287:AGCTG:A	acceptor_gain	1.0000
15:48341288:G:GA	acceptor_gain	1.0000
15:48341288:GC:G	acceptor_gain	1.0000
15:48341288:GCT:G	acceptor_gain	1.0000
15:48341288:GCTG:G	acceptor_gain	1.0000
15:48341288:GCTGG:G	acceptor_gain	1.0000
15:48341359:TGAAG:T	donor_loss	1.0000
15:48341362:AGGTA:A	donor_loss	1.0000
15:48341364:G:A	donor_loss	1.0000
15:48341365:T:G	donor_loss	1.0000
15:48341510:T:TA	acceptor_gain	1.0000
15:48341513:A:AG	acceptor_gain	1.0000
15:48341514:G:GA	acceptor_gain	1.0000
15:48341586:G:GG	donor_gain	1.0000
15:48334415:A:AG	acceptor_gain	0.9900
15:48334416:G:GG	acceptor_gain	0.9900
15:48334416:GT:G	acceptor_gain	0.9900
15:48334505:GTGG:G	donor_gain	0.9900
15:48336041:TTTA:T	acceptor_loss	0.9900
15:48336042:TTAGC:T	acceptor_loss	0.9900
15:48336043:TAGCT:T	acceptor_loss	0.9900
15:48336044:AGCT:A	acceptor_loss	0.9900
15:48336045:G:GA	acceptor_loss	0.9900

AlphaMissense

1597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:48341341:T:A	N203K	0.998
15:48341341:T:G	N203K	0.998
15:48341542:T:C	L220P	0.998
15:48342055:T:C	F246L	0.998
15:48342057:T:A	F246L	0.998
15:48342057:T:G	F246L	0.998
15:48334500:G:A	G168E	0.997
15:48341306:G:C	D192H	0.997
15:48341536:C:A	A218E	0.997
15:48332400:T:C	L138P	0.996
15:48332405:A:C	S140R	0.996
15:48334417:T:A	S140R	0.996
15:48334417:T:G	S140R	0.996
15:48336046:C:A	A171D	0.996
15:48341295:T:A	V188D	0.996
15:48341298:T:A	I189K	0.996
15:48341301:A:T	D190V	0.996
15:48341302:T:A	D190E	0.996
15:48341302:T:G	D190E	0.996
15:48341540:G:C	Q219H	0.996
15:48341540:G:T	Q219H	0.996
15:48332391:G:A	G135D	0.995
15:48332397:A:C	D137A	0.995
15:48336064:C:A	A177D	0.995
15:48341300:G:C	D190H	0.995
15:48341322:T:A	V197D	0.995
15:48341328:T:A	V199D	0.995
15:48341547:T:C	C222R	0.995
15:48332333:T:C	F116L	0.994
15:48332335:T:A	F116L	0.994

dbSNP variants (sampled 300 via entrez): RS1000573130 (15:48340162 G>C), RS1000625389 (15:48340411 C>T), RS1000785048 (15:48333216 G>T), RS1001102963 (15:48340836 C>T), RS1001133842 (15:48332947 A>C,T), RS1001310368 (15:48335136 T>G), RS1001476921 (15:48329579 A>G), RS1001521114 (15:48332286 C>T), RS1001970355 (15:48332550 A>G), RS1002035122 (15:48339696 T>A), RS1002086158 (15:48340051 G>A,C), RS1002158260 (15:48342167 C>A,T), RS1002174058 (15:48330631 C>T), RS1002317404 (15:48337004 T>C), RS1002448732 (15:48330977 A>G)

Disease associations

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

GenCC curated gene-disease

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

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 total (11 of 11 shown, 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 (top):

Study	Trait	p-value
GCST000189_46	Protein quantitative trait loci	3.000000e-06
GCST004219_4	Skin pigmentation	3.000000e-14
GCST006585_1503	Blood protein levels	2.000000e-11
GCST008839_52	Height	4.000000e-23

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement

MeSH disease descriptors (1)

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 (VIP=true, CPIC=false)

Binding affinities (BindingDB)

16 measured of 144 human assays (154 total across all organisms); most potent 16 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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-cyclopentyloxy-4-fluorophenyl)ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	40 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	50 nM	US-8883759: Anti-tumor effect potentiator
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
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide	IC50	90 nM	US-8883759: Anti-tumor effect potentiator
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
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
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
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
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
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
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
N-[5-[(2,4-dioxopyrimidin-1-yl)methoxy]-2-methylpentan-2-yl]-3-methoxybenzenesulfonamide	IC50	1120 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
US8530490, 99	IC50	1810 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
N-[2-[3-(cyclopropylmethoxy)phenyl]ethyl]-3-(2,4-dioxopyrimidin-1-yl)-N-methylpropane-1-sulfonamide	IC50	4540 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity
3-(2,4-dioxopyrimidin-1-yl)-N-methyl-N-[(1-phenylcyclopropyl)methyl]propane-1-sulfonamide	IC50	6560 nM	US-8530490: Uracil compound or salt thereof having human deoxyuridine triphosphatase inhibitory activity

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	affects cotreatment, decreases expression, increases expression	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 expression, decreases methylation	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	increases reaction, affects binding	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)

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

Trial	Phase	Status	Title
NCT01295047	PHASE4	COMPLETED	Comparison of Medical Therapies in Marfan Syndrome.
NCT00429364	PHASE3	COMPLETED	Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome
NCT00485368	PHASE3	COMPLETED	Angiotensin Converting Enzyme Inhibitors in Marfan Syndrome
NCT00683124	PHASE3	UNKNOWN	Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients
NCT00723801	PHASE3	COMPLETED	Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
NCT00763893	PHASE3	TERMINATED	Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
NCT00782327	PHASE3	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	PHASE3	UNKNOWN	Atenolol Versus Losartan in the Prevention of Progressive Dilation of the Aorta in Marfan Syndrome
NCT01361087	PHASE3	WITHDRAWN	Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome
NCT01715207	PHASE3	COMPLETED	Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS
NCT00593710	PHASE2	COMPLETED	Losartan Versus Atenolol for the Treatment of Marfan Syndrome
NCT00651235	PHASE2	UNKNOWN	A Randomized, Open-label, LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome
NCT01949233	PHASE2	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	ACTIVE_NOT_RECRUITING	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