NUDT1

Summary

NUDT1 (nudix hydrolase 1, HGNC:8048) is a protein-coding gene on chromosome 7p22.3, encoding Oxidized purine nucleoside triphosphate hydrolase (P36639). Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool.

Misincorporation of oxidized nucleoside triphosphates into DNA/RNA during replication and transcription can cause mutations that may result in carcinogenesis or neurodegeneration. The protein encoded by this gene is an enzyme that hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates, thereby preventing misincorporation. The encoded protein is localized mainly in the cytoplasm, with some in the mitochondria, suggesting that it is involved in the sanitization of nucleotide pools both for nuclear and mitochondrial genomes. Several alternatively spliced transcript variants, some of which encode distinct isoforms, have been identified. Additional variants have been observed, but their full-length natures have not been determined. A rare single-nucleotide polymorphism that results in the production of an additional, longer isoform (p26) has been described.

Source: NCBI Gene 4521 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 37 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002452

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8048
Approved symbol	NUDT1
Name	nudix hydrolase 1
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106268
Ensembl biotype	protein_coding
OMIM	600312
Entrez	4521

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000339737, ENST00000343985, ENST00000356714, ENST00000397046, ENST00000397048, ENST00000397049, ENST00000454650, ENST00000471348, ENST00000487426, ENST00000862416, ENST00000862417, ENST00000925089, ENST00000925090, ENST00000925091, ENST00000925092, ENST00000925093, ENST00000925094, ENST00000925095

RefSeq mRNA: 10 — MANE Select: NM_002452 NM_001367553, NM_001367554, NM_001367555, NM_002452, NM_198948, NM_198949, NM_198950, NM_198952, NM_198953, NM_198954

CCDS: CCDS5329, CCDS5330

Canonical transcript exons

ENST00000356714 — 4 exons

Exon	Start	End
ENSE00001380188	2250829	2251145
ENSE00001389247	2242226	2242256
ENSE00003478747	2244563	2244726
ENSE00003518047	2249857	2250002

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 95.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.0219 / max 94.0785, expressed in 1739 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76964	8.4987	1708
76965	0.7857	486
76967	0.3698	118
76968	0.3677	219

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.45	gold quality
right testis	UBERON:0004534	94.90	gold quality
left testis	UBERON:0004533	94.88	gold quality
ganglionic eminence	UBERON:0004023	94.84	gold quality
ventricular zone	UBERON:0003053	92.19	gold quality
testis	UBERON:0000473	91.96	gold quality
granulocyte	CL:0000094	91.87	gold quality
periodontal ligament	UBERON:0008266	91.81	gold quality
cortical plate	UBERON:0005343	90.92	gold quality
mucosa of transverse colon	UBERON:0004991	90.86	gold quality
monocyte	CL:0000576	90.51	gold quality
stromal cell of endometrium	CL:0002255	89.91	gold quality
mononuclear cell	CL:0000842	89.71	gold quality
leukocyte	CL:0000738	89.70	gold quality
tendon of biceps brachii	UBERON:0008188	89.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.47	gold quality
lower esophagus mucosa	UBERON:0035834	88.50	gold quality
skin of leg	UBERON:0001511	88.27	gold quality
skin of abdomen	UBERON:0001416	88.11	gold quality
spleen	UBERON:0002106	88.04	gold quality
esophagus mucosa	UBERON:0002469	87.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.00	gold quality
embryo	UBERON:0000922	86.69	gold quality
apex of heart	UBERON:0002098	86.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.07	gold quality
bone marrow	UBERON:0002371	85.84	gold quality
esophagus	UBERON:0001043	85.80	gold quality
lymph node	UBERON:0000029	85.75	gold quality
spinal cord	UBERON:0002240	85.71	gold quality
zone of skin	UBERON:0000014	85.60	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	23.47
E-GEOD-125970	yes	23.47
E-HCAD-13	yes	19.81
E-HCAD-1	yes	17.70
E-ANND-3	yes	8.15
E-CURD-88	no	3.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting NUDT1, 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-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-361-3P	99.19	66.45	1381

Literature-anchored findings (GeneRIF, showing 40)

• Trp-117 is essential for MTH1 to recognize both 8-oxo-dGTP and 2-hydroxy-dATP, whereas Asp-119 is only essential for recognizing 2-hydroxy-dATP, thus suggesting that origins of the substrate-binding pockets for MTH1 and MutT are different (PMID:11756418)
• 8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog. (PMID:11852070)
• Role of tryptophan residues in the recognition of mutagenic oxidized nucleotides by human antimutator MTH1 protein (PMID:12051941)
• These results suggested that increased expression of hMTH in peripheral lymphocytes may be a risk factor for prostate cancer and support our priori hypothesis. (PMID:12619034)
• cleaves 8-oxo-dGTP to 8-oxo-GMP, an unusable form for DNA synthesis (PMID:12717453)
• Elevated levels of hMTH1 protein is asociated with non-small-cell lung carcinomas (PMID:12757855)
• MTH1 protects cells from H2O2-induced cell dysfunction and death by hydrolyzing oxidized purine nucleotides including 8-oxo-dGTP and 2-OH-dATP. (PMID:12857738)
• dGDP and dADP, at physiological concentrations not exceeding 5 microM and GDP at mean concentration of 30 microM, taken together, can decrease the cellular hMTH1 enzymatic activity vs. 8-oxo-dGTP (PMID:12957652)
• These results clarify the effects of the anti/syn conformation and the functional groups on the 2 and 6 positions of the purine ring on the recognition by the human MTH1 protein. (PMID:15095864)
• study presents the solution structure of Nudix family hydrolase MTH1 solved by multidimensional heteronuclear NMR spectroscopy (PMID:15133035)
• the Met allele at codon 83 of MTH1 gene might be involved in the development of type 1 diabetes mellitus in the Japanese female population. (PMID:15516784)
• The amino terminal region of MTH1a functioned as a mitochondrial targeting signal when it was expressed in the HeLa cells as a fusion protein with enhanced green fluorescent protein. (PMID:16607562)
• In a case-control study, single nucleotide polymorphism of MTH1 was associated with increased small cell lung cancer risk. (PMID:16774934)
• Crystals of hMTH1-8-oxo-dGMP and hMTH1-2-oxo-dATP were diffracted at resolutions of 1.95 and 2.22 A, respectively. (PMID:17142918)
• These results suggested to us that the Thr45 allele of MTH1 might be associated with sporadic PD in the Chinese male population. (PMID:17917452)
• hMTH1 plays an important role in protecting cells against H(2)O(2)-induced apoptosis via a Noxa- and caspase-3/7-mediated signaling pathway, thus conferring a survival advantage through the inhibition of oxidative-stress-induced DNA damage (PMID:18708163)
• These results suggest that the single nucleotide polymorphisms of OGG1 and MTH1 may be cause of 8-hydroxy-2’-deoxyguanosine accumulation in the gastric mucosa. (PMID:18776649)
• Single nucleotide polymorphisms (SNPs) in hMTH1, hOGG1 and hMYH genes are associated with risk of chronic benzene poisoning. (PMID:18848840)
• human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP. (PMID:20144704)
• Manipulation of miR-145 expression modulates epidermal growth factor receptor (EGFR) and NUDT1 mRNA expressions. (PMID:21289483)
• Two rare variants (OGG1 c.137G>A; MUTYH c.1187G>A) and one common polymorphism (NUDT1 c.426C>T) were associated with colorectal cancer risk. (PMID:21355073)
• The expression levels of hMTH1 mRNA are highly correlated with hepatic levels of 8-oxo-dG and tail moment, suggesting that hMTH1 gene expression represents a molecular marker of oxidative DNA damage. (PMID:21421019)
• These results suggest that MTH1 deficiency might be a causative factor for aging and age-related disorders. (PMID:21538080)
• results indicate that the nucleotide pool is a significant target for UVA-induced mutations and implicates that hMTH1 plays an important role in protecting cells from UVA-induced oxidative stress (PMID:21784087)
• the structures of human MTH1 (1.9A) and its complex with the product 8-oxo-dGMP (PMID:21787772)
• The study provides insight into the influence of MTH1 levels on the epithelial-mesenchymal transition phenotype and Akt activation in RAS-transformed HMLE breast epithelial cells. (PMID:22790201)
• MutT homolog-1 attenuates oxidative DNA damage and delays photoreceptor cell death in inherited retinal degeneration. (PMID:22841817)
• Results suggest that the hMTH1-mediated maintenance of mtDNA stability protects cells from the susceptibility to oxidant injury associated with polyQ-expanded Htt, defends against 3-nitropropionic acid-induced neurodegeneration (PMID:22974734)
• X-ray crystallographic analysis of MTH1 protein structure (PMID:23295485)
• The risk of type 2 diabetes in the Chinese population is increased from the combined effects of AluYb8MUTYH with either hMTH1 c.247G>A or variants in the 5'-UTR of the hOGG1. (PMID:23396182)
• MTH1 protects cells from mutagenesis induced by ultraviolet ray A and B, but not ultraviolet ray C.hMTH1 prevents induction of transition-type mutations at AT and GC post ultraviolet ray A irradiation. (PMID:24144844)
• cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death; validation of MTH1 as an anticancer target in vivo (PMID:24695224)
• The ectopic expression of hMTH1 in the chloroplasts and mitochondria of Arabidopsis enhanced oxidative stress tolerance by activating the poly(ADP-ribosyl)ation (PAR)reaction and suppressing programmed cell death. (PMID:24928220)
• results indicate MTH1 is a novel and critical component of oncogenic KRAS-associated malignancy and its inhibition is likely to yield significant tumor-suppressive outcomes in KRAS-driven tumors. (PMID:25023700)
• Data suggest that hOGG1 could compensate for hMTH1 during oxidative DNA damage caused by H2O2, whereas hMTH1 could not compensate sufficiently for hOGG1 during the process. (PMID:25127756)
• MTH1 expression is required for effective transformation of epithelial cells by oncogenic HRAS. (PMID:25893378)
• a novel approach involving liquid chromatography-isotope-dilution tandem mass spectrometry to positively identify and accurately quantify MTH1 in human tissues, is reported. (PMID:26202347)
• MTH1 is the most prominent sanitizer of the cellular dNTP pool known to date. (PMID:26238318)
• Results show that MTH1 plays no role in protecting the cells against ultraviolet radiation-induced cytogenetic damage. (PMID:26520386)
• MTH-1 expression in colorectal cancer cells was upregulated via HIF-1alpha in response to hypoxic stress, emphasizing the crucial role of HIF-1alpha-induced MTH-1 in tumor growth. (PMID:26730155)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nudt1	ENSDARG00000030573
mus_musculus	Nudt1	ENSMUSG00000036639
rattus_norvegicus	Nudt1	ENSRNOG00000001260

Paralogs (3): NUDT12 (ENSG00000112874), NUDT17 (ENSG00000186364), NUDT18 (ENSG00000275074)

Protein

Protein identifiers

Oxidized purine nucleoside triphosphate hydrolase — P36639 (reviewed: P36639)

Alternative names: 2-hydroxy-dATP diphosphatase, 7,8-dihydro-8-oxoguanine triphosphatase, 8-oxo-dGTPase, Methylated purine nucleoside triphosphate hydrolase, Nucleoside diphosphate-linked moiety X motif 1

All UniProt accessions (2): P36639, C9J361

UniProt curated annotations — full annotation on UniProt →

Function. Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool. Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP. Also has a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP. Through the hydrolysis of oxidized purine nucleoside triphosphates, prevents their incorporation into DNA and the subsequent transversions A:T to C:G and G:C to T:A. Also catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA. Through this antimutagenic activity protects cells from oxidative stress.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol. Mitochondrion matrix. Nucleus Mitochondrion matrix.

Tissue specificity. Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes.

Post-translational modifications. The N-terminus is blocked.

Activity regulation. Inhibited by 2-oxo-dADP and 8-oxo-dGDP.

Cofactor. Binds 2 Mg(2+) ion per subunit.

Polymorphism. A polymorphism between Met-1 and Met-19 removes a stop codon before the initiation codon for isoform p22 and gives rise to the production of isoform p26. The allele frequency of isoform p26 is about 20%.

Miscellaneous. Contains a predicted transit peptide (1-18) for localization to the mitochondrion. Derived from a B-type mRNA with a polymorphic alteration (GU–>GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream.

Similarity. Belongs to the Nudix hydrolase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P36639-4	p18	yes
P36639-1	p26
P36639-2	p22
P36639-3	p21

RefSeq proteins (10): NP_001354482, NP_001354483, NP_001354484, NP_002443, NP_945186, NP_945187, NP_945188, NP_945190, NP_945191, NP_945192 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000086	NUDIX_hydrolase_dom	Domain
IPR003563	8ODP	Family
IPR015797	NUDIX_hydrolase-like_dom_sf	Homologous_superfamily
IPR020084	NUDIX_hydrolase_CS	Conserved_site
IPR020476	Nudix_hydrolase	Domain

Pfam: PF00293

Enzyme classification (BRENDA):

• EC 3.6.1.55 — 8-oxo-dGTP diphosphatase (BRENDA: 7 organisms, 58 substrates, 17 inhibitors, 12 Km, 2 kcat entries)
• EC 3.6.1.56 — 2-hydroxy-dATP diphosphatase (BRENDA: 4 organisms, 56 substrates, 35 inhibitors, 50 Km, 37 kcat entries)

Substrate kinetics (BRENDA)

29 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
8-OXO-DGTP	0.0084–12.8	12
2-HYDROXY-DATP	0.0043–5.7	8
8-OXO-DGTP	0.0001–0.48	4
8-OXO-DATP	0.0076–0.03	4
DGTP	0.046–258	4
2-OXO-DATP	0.0052–0.0318	3
8-OXO-GDP	—	2
8-OXO-DGDP	0.027	2
8-OXO-GTP	0.055–0.29	2
GTP	0.598–0.79	2
8-OXO-DGDP	0.0001	1
8-OXO-GTP	0.0003	1
DGDP	0.17	1
DGTP	1.1	1
GDP	0.35	1

Catalyzed reactions (Rhea), 7 shown:

• 8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H(+) (RHEA:31575)
• 2-oxo-dATP + H2O = 2-oxo-dAMP + diphosphate + H(+) (RHEA:31583)
• 8-oxo-dATP + H2O = 8-oxo-dAMP + diphosphate + H(+) (RHEA:65396)
• 2-oxo-ATP + H2O = 2-oxo-AMP + diphosphate + H(+) (RHEA:67392)
• O(6)-methyl-dGTP + H2O = O(6)-methyl-dGMP + diphosphate + H(+) (RHEA:67600)
• N(6)-methyl-dATP + H2O = N(6)-methyl-dAMP + diphosphate + H(+) (RHEA:67604)
• N(6)-methyl-ATP + H2O = N(6)-methyl-AMP + diphosphate + H(+) (RHEA:67608)

UniProt features (86 total): mutagenesis site 31, binding site 30, strand 11, helix 4, splice variant 3, sequence variant 2, turn 2, chain 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

124 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5WS7	X-RAY DIFFRACTION	1
6IJY	X-RAY DIFFRACTION	1.04
8I1F	X-RAY DIFFRACTION	1.05
8I1J	X-RAY DIFFRACTION	1.08
9XRI	X-RAY DIFFRACTION	1.08
9MBI	X-RAY DIFFRACTION	1.09
8I18	X-RAY DIFFRACTION	1.1
8I1E	X-RAY DIFFRACTION	1.1
7N03	X-RAY DIFFRACTION	1.13
5ANV	X-RAY DIFFRACTION	1.16
8I1G	X-RAY DIFFRACTION	1.18
8I1H	X-RAY DIFFRACTION	1.18
9MBK	X-RAY DIFFRACTION	1.18
5GHQ	X-RAY DIFFRACTION	1.18
5GHO	X-RAY DIFFRACTION	1.19
5GHP	X-RAY DIFFRACTION	1.19
4C9X	X-RAY DIFFRACTION	1.2
5GHJ	X-RAY DIFFRACTION	1.2
8I1D	X-RAY DIFFRACTION	1.2
8I1I	X-RAY DIFFRACTION	1.2
9MBG	X-RAY DIFFRACTION	1.2
6GLH	X-RAY DIFFRACTION	1.2
9MBH	X-RAY DIFFRACTION	1.21
5GHI	X-RAY DIFFRACTION	1.21
8I8T	X-RAY DIFFRACTION	1.22
5FSL	X-RAY DIFFRACTION	1.24
9FL6	X-RAY DIFFRACTION	1.3
6GLJ	X-RAY DIFFRACTION	1.3
6GLG	X-RAY DIFFRACTION	1.31
5ANW	X-RAY DIFFRACTION	1.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36639-F1	97.38	0.99

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 (30): 23; 23; 27; 33; 33; 33; 33; 35–38; 35–38; 35–38; 36; 52 …

Mutagenesis-validated functional residues (31):

Position	Phenotype
27	reduces 2-oxo-datpase and 8-oxo-dgtpase activities.
36	reduces activity by 97%.
37	loss of activity.
39	loss of activity.
40	reduces activity by 97%.
42	reduces activity by 60%.
45	loss of activity.
47	loss of activity.
48	loss of activity.
49	loss of activity.
53	loss of activity.
54	loss of activity.
55	loss of activity.
56	loss of ability to prevent dna damage. expected to cause loss of enzyme activity.
56	loss of activity.
57	loss of activity.
117	greatly reduces or abolishes 2-oxo-datpase and 8-oxo-dgtpase activities.
117	enhances 2-oxo-datpase activity and greatly reduces 8-oxo-dgtpase activity.
119	loss of 2-oxo-datpase activity, reduces 8-oxo-dgtpase activity.
120	mildly decreased 2-oxo-datpase activity, nearly abolishes 8-oxo-dgtpase activity.
150	reduces 2-oxo-datpase and 8-oxo-dgtpase activities and increases thermolability.
151–156	almost abolishes 2-oxo-datpase and 8-oxo-dgtpase activities and increases thermolability.
151	reduces 2-oxo-datpase and 8-oxo-dgtpase activities and increases thermolability.
152–156	greatly reduces 2-oxo-datpase and 8-oxo-dgtpase activities and increases thermolability.
152	reduces 2-oxo-datpase and 8-oxo-dgtpase activities and increases thermolability.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2393930	Phosphate bond hydrolysis by NUDT proteins

MSigDB gene sets: 219 (showing top): MORF_DNMT1, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_ESPL1, MORF_UBE2I, MORF_RRM1, MORF_HDAC1, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MORF_CDK2, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, MODULE_16, KAUFFMANN_DNA_REPAIR_GENES, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, chr7p22

GO Biological Process (4): purine nucleoside catabolic process (GO:0006152), DNA repair (GO:0006281), response to oxidative stress (GO:0006979), DNA protection (GO:0042262)

GO Molecular Function (14): 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity (GO:0008413), dATP diphosphatase activity (GO:0008828), hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides (GO:0016818), snoRNA binding (GO:0030515), 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity (GO:0035539), metal ion binding (GO:0046872), ATP diphosphatase activity (GO:0047693), 2-hydroxy-ATP hydrolase activity (GO:0106377), 2-hydroxy-dATP hydrolase activity (GO:0106378), N6-methyl-(d)ATP hydrolase activity (GO:0106431), O6-methyl-dGTP hydrolase activity (GO:0106433), RNA binding (GO:0003723), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Purine catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside triphosphate diphosphatase activity	6
DNA metabolic process	2
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
nucleoside catabolic process	1
purine nucleoside metabolic process	1
purine-containing compound catabolic process	1
DNA damage response	1
response to stress	1
cellular response to stress	1
hydrolase activity, acting on acid anhydrides	1
RNA binding	1
cation binding	1
nucleic acid binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDT1	MUTYH	Q9UIF7	927
NUDT1	OGG1	P78554	922
NUDT1	NUDT18	Q6ZVK8	765
NUDT1	NUDT15	Q9NV35	762
NUDT1	NUDT5	Q9UKK9	761
NUDT1	NUDT22	Q9BRQ3	641
NUDT1	NUDT14	O95848	620
NUDT1	NUDT2	P50583	599
NUDT1	NTPCR	Q9BSD7	592
NUDT1	NUDT17	P0C025	587
NUDT1	NUDT13	Q86X67	587
NUDT1	NEIL1	Q96FI4	572
NUDT1	PRDX1	P35703	565
NUDT1	NUDT12	Q9BQG2	532
NUDT1	NUDT4B	A0A024RBG1	521

IntAct

26 interactions, top by confidence:

A	B	Type	Score
NUDT1	HEL-S-5	psi-mi:“MI:0915”(physical association)	0.560
HEL-S-5	NUDT1	psi-mi:“MI:0915”(physical association)	0.560
NUDT1	ACY1	psi-mi:“MI:0915”(physical association)	0.550
NUDT1	ACY1	psi-mi:“MI:0915”(physical association)	0.370
CFTR	NUDT1	psi-mi:“MI:0915”(physical association)	0.370
	ABL1	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
MAP1LC3B		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
NUDT1	TNFSF14	psi-mi:“MI:0914”(association)	0.350
NUDT1	GP9	psi-mi:“MI:0914”(association)	0.350
	NUDT1	psi-mi:“MI:0914”(association)	0.350
	QDPR	psi-mi:“MI:0914”(association)	0.350
NTHL1	NUDT1	psi-mi:“MI:0915”(physical association)	0.000
NUDT1	MRM3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (92): NUDT1 (Two-hybrid), NUDT1 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), RRAGB (Affinity Capture-MS), NUDT1 (Affinity Capture-MS), RNMTL1 (Affinity Capture-MS), NUDT1 (Affinity Capture-MS), NUDT1 (Affinity Capture-MS), NUDT1 (Affinity Capture-RNA), FMNL3 (Two-hybrid), TRMT12 (Two-hybrid), ACY1 (Two-hybrid), NUDT1 (Affinity Capture-MS), NUDT1 (Affinity Capture-RNA)

ESM2 similar proteins: A1WXH5, A4WE41, A5UA57, A5UGU3, A8GDW2, A8LQ20, A9N3L5, B4T534, B4TUQ7, B5BFK4, B5F5G3, B5F9P6, B5RE00, C0SPC3, F1P963, O42641, P26173, P35640, P36639, P41354, P44635, P44710, P44932, P50619, P53368, P53369, P60923, Q10132, Q16DR2, Q17VH2, Q28W27, Q4QNB3, Q55928, Q5E7U8, Q5LWT6, Q5NWG5, Q5PL31, Q65W71, Q6D3F5, Q6FDK3

Diamond homologs: A6V6Z8, B7VB54, F1P963, O86062, P36639, P41354, P53368, P53369, P59659, Q02KW6, Q29RH3, Q4R7L8, Q5RD76, Q7ZWC3, Q8BG93, Q9BQG2, Q9DCN1, P9WIY0, P9WIY1, Q9NV35, B5XYE2, P46351, P54570, P95781, P9WIX8, P9WIX9, Q58549, Q83IS3, Q99MY2, Q9CA40, Q9RVK2, A5F3M9, A5UA57, A5UGU3, B7VM66, C3LR63, P44710, Q48IH8, Q4QNB3, Q7NTZ8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SKP2	“down-regulates quantity by destabilization”	NUDT1	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	NUDT1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	8	16.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	5	8.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

834 predictions. Top by Δscore:

Variant	Effect	Δscore
7:2242255:AGGTA:A	donor_loss	1.0000
7:2242256:GGTA:G	donor_loss	1.0000
7:2249852:CGCA:C	acceptor_loss	1.0000
7:2249853:GCA:G	acceptor_loss	1.0000
7:2249854:CA:C	acceptor_loss	1.0000
7:2249855:A:C	acceptor_loss	1.0000
7:2249855:AG:A	acceptor_gain	1.0000
7:2249856:GG:G	acceptor_gain	1.0000
7:2249856:GGGA:G	acceptor_gain	1.0000
7:2249998:CGACG:C	donor_gain	1.0000
7:2249999:GACG:G	donor_gain	1.0000
7:2249999:GACGG:G	donor_gain	1.0000
7:2250000:ACG:A	donor_gain	1.0000
7:2250001:CG:C	donor_gain	1.0000
7:2250001:CGGT:C	donor_loss	1.0000
7:2250002:GG:G	donor_gain	1.0000
7:2250003:G:GC	donor_loss	1.0000
7:2250003:G:GG	donor_gain	1.0000
7:2250004:T:G	donor_loss	1.0000
7:2250819:ATT:A	acceptor_gain	1.0000
7:2250821:T:A	acceptor_gain	1.0000
7:2242257:G:A	donor_loss	0.9900
7:2244558:TTCAG:T	acceptor_loss	0.9900
7:2244559:TCA:T	acceptor_loss	0.9900
7:2244561:A:AG	acceptor_gain	0.9900
7:2244561:AGA:A	acceptor_loss	0.9900
7:2244562:G:GA	acceptor_gain	0.9900
7:2244562:GA:G	acceptor_gain	0.9900
7:2244724:GAGGT:G	donor_loss	0.9900
7:2244725:AGG:A	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000242818 (7:2244493 C>G,T), RS1000243094 (7:2249122 G>T), RS1000310764 (7:2243017 T>A), RS1000578485 (7:2245422 G>A), RS1000588860 (7:2248893 A>T), RS1000625228 (7:2250838 C>A,T), RS1001120038 (7:2241076 A>C), RS1001210819 (7:2249749 G>C,T), RS1001237146 (7:2241286 A>G), RS1001566991 (7:2245139 A>G,T), RS1001802376 (7:2245771 C>G), RS1001864714 (7:2241431 C>A,G), RS1002018220 (7:2250128 C>A,G,T), RS1002069013 (7:2250269 A>G), RS1002158242 (7:2246014 C>T)

Disease associations

OMIM: gene MIM:600312 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001565_9	Schizophrenia	2.000000e-09
GCST002149_3	Schizophrenia	6.000000e-13
GCST004521_264	Autism spectrum disorder or schizophrenia	7.000000e-16
GCST005759_5	Dimensional psychopathology (Social)	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009100	social domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3708265 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 75,220 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1282	IMIQUIMOD	4	56,604
CHEMBL383322	RESIQUIMOD	2	18,616

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

ChEMBL bioactivities

187 potent at pChembl≥5 of 204 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.37	IC50	0.043	nM	CHEMBL4436749
10.22	IC50	0.06	nM	CHEMBL4570266
10.10	IC50	0.08	nM	CHEMBL4778773
10.00	IC50	0.1	nM	CHEMBL4083992
10.00	IC50	0.1	nM	CHEMBL4070624
9.96	IC50	0.11	nM	CHEMBL4460228
9.82	IC50	0.15	nM	CHEMBL4435945
9.77	IC50	0.17	nM	CHEMBL4529335
9.70	IC50	0.2	nM	CHEMBL3781661
9.70	IC50	0.2	nM	CHEMBL3780962
9.70	Kd	0.2	nM	CHEMBL3792684
9.70	Kd	0.2	nM	CHEMBL4747532
9.52	IC50	0.3	nM	CHEMBL4747532
9.48	IC50	0.33	nM	CHEMBL4460446
9.40	Kd	0.4	nM	CHEMBL3794167
9.31	IC50	0.49	nM	CHEMBL4435983
9.30	IC50	0.5	nM	CHEMBL3780596
9.30	IC50	0.5	nM	CHEMBL3780613
9.30	IC50	0.5	nM	CHEMBL3792684
9.30	IC50	0.5	nM	CHEMBL3794167
9.30	Kd	0.5	nM	CHEMBL4783492
9.30	IC50	0.5	nM	CHEMBL4776026
9.22	IC50	0.6	nM	CHEMBL3780032
9.21	IC50	0.61	nM	CHEMBL4577002
9.15	IC50	0.7	nM	CHEMBL4537820
9.10	IC50	0.8	nM	CHEMBL3781316
9.10	IC50	0.8	nM	CHEMBL4096813
9.10	IC50	0.8	nM	CHEMBL4565830
9.10	IC50	0.8	nM	CHEMBL4784602
9.09	IC50	0.82	nM	CHEMBL4534555
9.05	IC50	0.9	nM	CHEMBL3781316
9.05	IC50	0.9	nM	CHEMBL4783492
9.00	IC50	1	nM	CHEMBL4072758
8.96	IC50	1.1	nM	CHEMBL4464305
8.85	IC50	1.4	nM	CHEMBL4754128
8.80	IC50	1.6	nM	CHEMBL3781316
8.74	IC50	1.8	nM	CHEMBL3780321
8.70	IC50	2	nM	CHEMBL4094381
8.70	EC50	1.995	nM	CHEMBL4091768
8.70	EC50	1.995	nM	CHEMBL4073623
8.70	IC50	2	nM	CHEMBL4749068
8.64	IC50	2.3	nM	CHEMBL4096813
8.52	EC50	3	nM	CHEMBL3794167
8.52	Kd	3	nM	CHEMBL4799076
8.52	IC50	3	nM	CHEMBL3782004
8.51	IC50	3.1	nM	CHEMBL3781917
8.43	IC50	3.7	nM	CHEMBL4437933
8.39	IC50	4.1	nM	CHEMBL4439723
8.39	IC50	4.1	nM	CHEMBL3781316
8.35	IC50	4.5	nM	CHEMBL3781015

PubChem BioAssay actives

204 with measured affinity, of 297 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-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]acetamide	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	<0.0001	uM
N-ethyl-4-[2-(2-methoxypropan-2-yl)pyrrolidin-1-yl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
N-ethyl-4-(2-pyridin-3-ylpyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
4-(3-cyclopropylmorpholin-4-yl)-N-ethyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
N-cyclopropyl-4-(2-pyridin-2-ylpyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
N-(oxetan-3-yl)-4-(2-pyridin-3-ylpyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
N-ethyl-4-(3-phenylmorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
N-(oxetan-3-yl)-4-(2-pyridin-2-ylpyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
N-ethyl-4-(2-phenylpyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
N-ethyl-4-(2-pyridin-2-ylpyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0001	uM
methyl N-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]carbamate	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0001	uM
N-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]cyclobutanecarboxamide	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0001	uM
[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]urea	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0001	uM
N-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]-2,2-difluoroacetamide	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0001	uM
1-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]-3-methylurea	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0001	uM
N-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]cyclopropanecarboxamide	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0001	uM
4-anilino-7-methoxy-N-methyl-6-[(4-methylpiperazin-1-yl)methoxy]quinoline-3-carboxamide	1679179: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay	ic50	0.0001	uM
4-(2,2-dimethylpropoxy)-5-methylpyrimidin-2-amine	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0002	uM
4-anilino-6,7-dimethoxy-N-methylquinoline-3-carboxamide	1679166: Binding affinity to recombinant His-tagged MTH1 isoform p18 (M1 to V156 residues) (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0002	uM
N-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]propanamide	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0002	uM
17-(methylamino)-8,14-dioxa-1,16,19,22-tetrazatetracyclo[13.5.2.13,7.018,21]tricosa-3(23),4,6,15,17,21-hexaen-20-one	1679166: Binding affinity to recombinant His-tagged MTH1 isoform p18 (M1 to V156 residues) (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0002	uM
4-N-(2,2-dimethylpropyl)-4-N,5-dimethylpyrimidine-2,4-diamine	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0002	uM
N-[6-(2,3-dimethylphenyl)-4-(methylamino)-2-pyridinyl]acetamide	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0003	uM
17-(methylamino)-8,11,14-trioxa-1,16,19,22-tetrazatetracyclo[13.5.2.13,7.018,21]tricosa-3(23),4,6,15,17,21-hexaen-20-one	1679166: Binding affinity to recombinant His-tagged MTH1 isoform p18 (M1 to V156 residues) (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0004	uM
4-(4-chloro-2-fluoroanilino)-6,7-dimethoxy-N-methylquinoline-3-carboxamide	1679166: Binding affinity to recombinant His-tagged MTH1 isoform p18 (M1 to V156 residues) (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0005	uM
3-[(2-amino-5-methylpyrimidin-4-yl)-methylamino]-2,2-dimethylpropan-1-ol	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0005	uM
4-N,6-N-dimethyl-4-N-[(1S)-1-phenylethyl]pyrimidine-2,4,6-triamine	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0005	uM
6,7-dimethoxy-N-methyl-4-[2-(2-methylsulfonylethyl)anilino]quinoline-3-carboxamide	1679179: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay	ic50	0.0005	uM
4-N-(2,2-dimethylpropyl)-5-methylpyrimidine-2,4-diamine	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0005	uM
3-(2-amino-5-methylpyrimidin-4-yl)oxy-2,2-dimethylpropan-1-ol	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0006	uM
N-[5-(2,3-dimethylphenyl)-1,2,3,4-tetrahydro-1,6-naphthyridin-7-yl]-2-methylpropanamide	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0006	uM
4-N-methyl-6-[(1S)-1-phenylethoxy]pyrimidine-2,4-diamine	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0007	uM
N-ethyl-4-[(3S)-3-methylmorpholin-4-yl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0008	uM
16-(methylamino)-8,13-dioxa-1,15,18,21-tetrazatetracyclo[12.5.2.13,7.017,20]docosa-3(22),4,6,14,16,20-hexaen-19-one	1679179: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay	ic50	0.0008	uM
4-N-methyl-6-piperidin-1-ylpyrimidine-2,4-diamine	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0008	uM
6-(2,3-dichlorophenyl)-4-N-methylpyrimidine-2,4-diamine	1287271: Inhibition of recombinant human MTH1 assessed as hydrolysis of dGTP to dGMP and pyrophosphate after 15 mins by malachite green-based microplate reader analysis	ic50	0.0008	uM
6-(3,4-dihydro-1H-isoquinolin-2-yl)-4-N-methylpyrimidine-2,4-diamine	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0008	uM
4-(2-phenylpyrrolidin-1-yl)-1H-pyrazolo[3,4-b]pyridine	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0010	uM
6-(3,4-dihydro-2H-quinolin-1-yl)-4-N-methylpyrimidine-2,4-diamine	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0011	uM
17-(methylamino)-8,14-dioxa-1,11,16,19,22-pentazatetracyclo[13.5.2.13,7.018,21]tricosa-3(23),4,6,15,17,21-hexaene-10,20-dione	1679179: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay	ic50	0.0014	uM
4-(3,3-dimethylbutyl)-5-methylpyrimidin-2-amine	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0018	uM
3-phenyl-4-(1H-pyrazolo[3,4-b]pyridin-4-yl)morpholine	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0020	uM
4-(4-chloro-2-fluoroanilino)-N-methylquinoline-3-carboxamide	1679179: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay	ic50	0.0020	uM
4-[4-[2-(dimethylamino)ethyl]phenyl]quinazolin-2-amine	1679166: Binding affinity to recombinant His-tagged MTH1 isoform p18 (M1 to V156 residues) (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0030	uM
4-N-cyclopropyl-6-(2,3-dichlorophenyl)pyrimidine-2,4-diamine	1679179: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay	ic50	0.0030	uM
3-[(2-amino-5-methylpyrimidin-4-yl)amino]-2,2-dimethylpropan-1-ol	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0031	uM
4-N-methyl-6-pyrrolidin-1-ylpyrimidine-2,4-diamine	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0037	uM
5-(2,3-dichlorophenyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-amine	1547865: Inhibition of human recombinant human His-tagged MTH1 expressed in Escherichia coli BL21 (DE3) using 8-oxo-dGTP as substrate incubated for 15 mins followed by substrate addition and measured after 3 hrs by PPiLight Inorganic Pyrophosphate assay kit method	ic50	0.0041	uM
3-[(2-amino-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)oxy]-2,2-dimethylpropan-1-ol	1287270: Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	ic50	0.0045	uM
4-(2-phenylpyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine	1455579: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay	ic50	0.0050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Oxygen	decreases expression	2
Paraquat	decreases response to substance, decreases expression	2
Valproic Acid	decreases expression, increases methylation	2
Cyclosporine	affects expression, decreases expression	2
dicrotophos	decreases expression	1
beauvericin	affects cotreatment, increases expression	1
bisphenol A	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
cerous chloride	affects cotreatment, decreases expression	1
lanthanum chloride	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
enniatins	affects cotreatment, increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	increases expression	1
riccardin D	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Troglitazone	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzene	increases response to substance	1

ChEMBL screening assays

55 unique, capped per target: 52 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3782136	Binding	Inhibition of recombinant MTH1 (unknown origin) assessed as hydrolysis of 8-oxodGTP to 8-oxodGMP and pyrophosphate by PPiLight assay	Identification of potent and selective MTH1 inhibitors. — Bioorg Med Chem Lett
CHEMBL5723292	Functional	Affinity Biochemical interaction: (inhibition of dGTP substrate hydrolysis, use malachite green to measure absorbance from released inorganic phosphate) EUB0000089c NUDT1	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3CZ	Abcam HEK293T NUDT1 KO	Transformed cell line	Female
CVCL_RQ86	HAP1 NUDT1 (-) 1	Cancer cell line	Male
CVCL_SA83	HAP1 NUDT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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