NUDT3

Summary

NUDT3 (nudix hydrolase 3, HGNC:8050) is a protein-coding gene on chromosome 6p21.31, encoding Diphosphoinositol polyphosphate phosphohydrolase 1 (O95989). Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction.

NUDT3 belongs to the MutT, or Nudix, protein family. Nudix proteins act as homeostatic checkpoints at important stages in nucleoside phosphate metabolic pathways, guarding against elevated levels of potentially dangerous intermediates, like 8-oxo-dGTP, which promotes AT-to-CG transversions (Safrany et al., 1998 [PubMed 9822604]).

Source: NCBI Gene 11165 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 6 total
• Druggable target: yes
• MANE Select transcript: NM_006703

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8050
Approved symbol	NUDT3
Name	nudix hydrolase 3
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	DIPP
Ensembl gene	ENSG00000272325
Ensembl biotype	protein_coding
OMIM	609228
Entrez	11165

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000607016, ENST00000899846, ENST00000899847, ENST00000899848, ENST00000914237, ENST00000914238

RefSeq mRNA: 1 — MANE Select: NM_006703 NM_006703

CCDS: CCDS4791

Canonical transcript exons

ENST00000607016 — 5 exons

Exon	Start	End
ENSE00001423013	34392264	34392669
ENSE00003536541	34293451	34293535
ENSE00003565746	34295641	34295685
ENSE00003625979	34341862	34341972
ENSE00003694816	34279679	34288931

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.7397 / max 1978.3497, expressed in 1826 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73236	44.9056	1824
73235	4.9083	1621
73233	4.8417	1624
73232	0.6726	314
73237	0.4556	219
73239	0.4153	181
73240	0.3151	136
73238	0.1186	50
73234	0.1069	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.09	gold quality
inferior olivary complex	UBERON:0002127	98.67	gold quality
postcentral gyrus	UBERON:0002581	98.66	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.54	gold quality
parietal lobe	UBERON:0001872	98.36	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.31	gold quality
middle frontal gyrus	UBERON:0002702	98.25	gold quality
CA1 field of hippocampus	UBERON:0003881	98.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.09	gold quality
lateral globus pallidus	UBERON:0002476	98.01	gold quality
entorhinal cortex	UBERON:0002728	97.84	gold quality
medial globus pallidus	UBERON:0002477	97.71	gold quality
frontal pole	UBERON:0002795	97.61	gold quality
globus pallidus	UBERON:0001875	97.58	gold quality
substantia nigra pars compacta	UBERON:0001965	97.46	gold quality
medulla oblongata	UBERON:0001896	97.29	gold quality
olfactory bulb	UBERON:0002264	97.20	silver quality
paraflocculus	UBERON:0005351	97.20	gold quality
cerebellar vermis	UBERON:0004720	97.17	gold quality
superior vestibular nucleus	UBERON:0007227	97.09	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.95	gold quality
orbitofrontal cortex	UBERON:0004167	96.90	gold quality
superior frontal gyrus	UBERON:0002661	96.86	gold quality
triceps brachii	UBERON:0001509	96.82	gold quality
pons	UBERON:0000988	96.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.76	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.67	gold quality
ventral tegmental area	UBERON:0002691	96.64	gold quality
corpus epididymis	UBERON:0004359	96.60	gold quality
cranial nerve II	UBERON:0000941	96.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.85
E-ENAD-27	no	392.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting NUDT3, 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-3925-3P	100.00	69.95	1237
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6515-3P	99.82	68.19	1933

Literature-anchored findings (GeneRIF, showing 7)

• results suggest that NUDT3 rs206936 is associated with body mass index in Japanese women (PMID:23708086)
• Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals (PMID:26932476)
• NUDT3 and KLF5 were found to associate with lean mass and HLA-DQB1-AS1 for hand grip strength as candidate genes to target for these phenotypes in sarcopenia. The associated regulatory SNPs are rs464553, rs1028883 and rs3129753 respectively. (PMID:32093658)
• InsP7 is a small-molecule regulator of NUDT3-mediated mRNA decapping and processing-body dynamics. (PMID:32727897)
• New structural insights reveal an expanded reaction cycle for inositol pyrophosphate hydrolysis by human DIPP1. (PMID:33475202)
• Polyphosphate degradation by Nudt3-Zn(2+) mediates oxidative stress response. (PMID:34788624)
• Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases. (PMID:37466765)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nudt3a	ENSDARG00000016256
danio_rerio	nudt3b	ENSDARG00000042123
mus_musculus	Nudt3	ENSMUSG00000024213
rattus_norvegicus	Nudt3	ENSRNOG00000061176

Paralogs (4): NUDT10 (ENSG00000122824), NUDT4 (ENSG00000173598), NUDT4B (ENSG00000177144), NUDT11 (ENSG00000196368)

Protein

Protein identifiers

Diphosphoinositol polyphosphate phosphohydrolase 1 — O95989 (reviewed: O95989)

Alternative names: Diadenosine hexaphosphate hydrolase, Endopolyphosphatase, Nucleoside diphosphate-linked moiety X motif 3, m7GpppN-mRNA hydrolase, m7GpppX diphosphatase

All UniProt accessions (1): O95989

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphosphate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with diadenosine 5’,5’’’-P1,P6-hexaphosphate (Ap6A) and diadenosine 5’,5’’’- P1,P5-pentaphosphate (Ap5A) being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Acts as a decapping enzyme that modulates the stability of a subset of mRNAs implicated in cell motility. Hydrolyzes monomethylated capped RNA after both the alpha- and beta-phosphates generating m7GMP + ppRNA and m7GDP + pRNA. Can hydrolyze unmethylated capped RNAs. Divalent cations zinc, magnesium and manganese determine its substrate specificity. Exhibits diphosphoinositol polyphosphate phosphohydrolase in the presence of magnesium ions, diadenosine hexaphosphate hydrolase activity in the presence of manganese ions and endopolyphosphatase activity in the presence of zinc ions. Plays an important role in limiting DNA damage and maintaining cell survival upon oxidative stress via its endopolyphosphatase activity.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed. Expressed at higher level in brain, heart, pancreas and liver. Also expressed in placenta, lung and kidney.

Activity regulation. Endopolyphospahatase activity is inhibited by NaF, NaPPi, beta-glycerol phosphate and heparin. 5-diphosphoinositol pentakisphosphate (5-InsP7) inhibits its mRNA decapping activity.

Cofactor. Binds 3 Mg(2+) ions per subunit.

Similarity. Belongs to the Nudix hydrolase family. DIPP subfamily.

RefSeq proteins (1): NP_006694* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000086	NUDIX_hydrolase_dom	Domain
IPR015797	NUDIX_hydrolase-like_dom_sf	Homologous_superfamily
IPR020084	NUDIX_hydrolase_CS	Conserved_site
IPR047198	DDP-like_NUDIX	Domain

Pfam: PF00293

Enzyme classification (BRENDA):

• EC 3.6.1.17 — bis(5’-nucleosyl)-tetraphosphatase (asymmetrical) (BRENDA: 21 organisms, 54 substrates, 68 inhibitors, 70 Km, 50 kcat entries)
• EC 3.6.1.42 — guanosine-diphosphatase (BRENDA: 12 organisms, 49 substrates, 14 inhibitors, 6 Km, 1 kcat entries)
• EC 3.6.1.52 — diphosphoinositol-polyphosphate diphosphatase (BRENDA: 7 organisms, 75 substrates, 14 inhibitors, 14 Km, 20 kcat entries)
• EC 3.6.1.60 — diadenosine hexaphosphate hydrolase (AMP-forming) (BRENDA: 3 organisms, 19 substrates, 9 inhibitors, 9 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
AP4A	0.0041–10	28
P1,P4-BIS(5’-ADENOSYL) TETRAPHOSPHATE	0.0007–0.054	8
DIADENOSINE 5’,5’’-P1,P4-TETRAPHOSPHATE	0.005–0.407	6
DIPHOSPHOINOSITOL PENTAKISPHOSPHATE	—	6
P1,P5-BIS(5’-ADENOSYL)PENTAPHOSPHATE	0.0077–0.05	6
P1,P4-BIS(5’-GUANOSYL) TETRAPHOSPHATE	0.001–1.03	4
5’,5’’-DIADENOSINE TETRAPHOSPHATE	0.0006–0.003	3
GDP	0.0005–0.1	3
P1,P6-BIS(5’-ADENOSYL)HEXAPHOSPHATE	0.0059–0.61	3
5’,5’-DIADENOSINE TETRAPHOSPHATE	0.009–0.012	2
DIADENOSINE 5’,5’-P1,P4-TETRAPHOSPHATE	0.002–0.0025	2
P1,P4-BIS(5’-URIDYL) TETRAPHOSPHATE	0.01–0.011	2
P1,P4-BIS(5’-XANTHOSYL) TETRAPHOSPHATE	0.016–0.018	2
UDP	0.0006–0.0744	2
2-OXO-DATP	0.3846	1

Catalyzed reactions (Rhea), 8 shown:

• 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + H2O = 1D-myo-inositol hexakisphosphate + phosphate + H(+) (RHEA:22384)
• phosphate + n H2O = (n+1) phosphate + n H(+) (RHEA:22452)
• P(1),P(5)-bis(5’-adenosyl) pentaphosphate + H2O = ADP + ATP + 2 H(+) (RHEA:30527)
• P(1),P(4)-bis(5’-adenosyl) tetraphosphate + H2O = AMP + ATP + 2 H(+) (RHEA:32039)
• P(1),P(6)-bis(5’-adenosyl) hexaphosphate + H2O = 2 ATP + 2 H(+) (RHEA:32043)
• 3,5-bis(diphospho)-1D-myo-inositol 1,2,4,6-tetrakisphosphate + H2O = 3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate + phosphate + 2 H(+) (RHEA:56312)
• a 5’-end (N(7)-methyl 5’-triphosphoguanosine)-ribonucleoside in mRNA + H2O = N(7)-methyl-GMP + a 5’-end diphospho-ribonucleoside in mRNA + 2 H(+) (RHEA:65388)
• a 5’-end (N(7)-methyl 5’-triphosphoguanosine)-ribonucleoside in mRNA + H2O = N(7)-methyl-GDP + a 5’-end phospho-ribonucleoside in mRNA + 2 H(+) (RHEA:67484)

UniProt features (42 total): mutagenesis site 14, binding site 10, strand 7, helix 4, turn 2, chain 1, domain 1, modified residue 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
6PCK	X-RAY DIFFRACTION	1.2
2FVV	X-RAY DIFFRACTION	1.25
6PCL	X-RAY DIFFRACTION	1.3
8T98	X-RAY DIFFRACTION	1.3
6WOC	X-RAY DIFFRACTION	1.35
6WOD	X-RAY DIFFRACTION	1.35
6WO7	X-RAY DIFFRACTION	1.4
6WOE	X-RAY DIFFRACTION	1.4
8G9C	X-RAY DIFFRACTION	1.4
8TFA	X-RAY DIFFRACTION	1.4
6WOB	X-RAY DIFFRACTION	1.45
6WOA	X-RAY DIFFRACTION	1.5
6WOG	X-RAY DIFFRACTION	1.5
6WOI	X-RAY DIFFRACTION	1.5
8T99	X-RAY DIFFRACTION	1.5
8TF9	X-RAY DIFFRACTION	1.55
6WOF	X-RAY DIFFRACTION	1.6
8G9D	X-RAY DIFFRACTION	1.6
2Q9P	X-RAY DIFFRACTION	1.65
6WO8	X-RAY DIFFRACTION	1.7
6WOH	X-RAY DIFFRACTION	1.7
7TN4	X-RAY DIFFRACTION	1.85
6WO9	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95989-F1	87.68	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 69 (proton acceptor)

Ligand- & substrate-binding residues (10): 70; 89–91; 115; 133; 10; 18–20; 39–41; 50; 66; 66

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (14):

Position	Phenotype
50	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
51	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
52	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
66	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
69–70	loss of mrna-decapping activity.
70	loss of endopolyphosphatase activity.
70	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
72	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
75	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
78	no effect on diphosphoinositol polyphosphate phosphohydrolase activity.
78	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
82	loss of diphosphoinositol polyphosphate phosphohydrolase activity.
84	induces a strong decrease in ap6a and [pp]-insp4 hydrolysis, while it only weakly affects pp-insp5 hydrolysis.
91	induces a strong decrease in ap6a and [pp]-insp4 hydrolysis, while it only weakly affects pp-insp5 hydrolysis.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1855167	Synthesis of pyrophosphates in the cytosol

MSigDB gene sets: 233 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MORF_RAGE, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_POLYOL_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KAUFFMANN_DNA_REPAIR_GENES, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (8): cell-cell signaling (GO:0007267), diadenosine polyphosphate catabolic process (GO:0015961), diphosphoinositol polyphosphate metabolic process (GO:0071543), diphosphoinositol polyphosphate catabolic process (GO:0071544), RNA decapping (GO:0110154), diadenosine pentaphosphate catabolic process (GO:1901907), diadenosine hexaphosphate catabolic process (GO:1901909), adenosine 5’-(hexahydrogen pentaphosphate) catabolic process (GO:1901911)

GO Molecular Function (17): magnesium ion binding (GO:0000287), endopolyphosphatase activity (GO:0000298), zinc ion binding (GO:0008270), diphosphoinositol-polyphosphate diphosphatase activity (GO:0008486), manganese ion binding (GO:0030145), bis(5’-adenosyl)-hexaphosphatase activity (GO:0034431), bis(5’-adenosyl)-pentaphosphatase activity (GO:0034432), inositol diphosphate tetrakisphosphate diphosphatase activity (GO:0052840), inositol diphosphate pentakisphosphate diphosphatase activity (GO:0052842), inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity (GO:0052845), inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity (GO:0052848), 5’-(N(7)-methyl 5’-triphosphoguanosine)-[mRNA] diphosphatase activity (GO:0140932), 5’-(N(7)-methylguanosine 5’-triphospho)-[mRNA] hydrolase activity (GO:0140933), protein binding (GO:0005515), pyrophosphatase activity (GO:0016462), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Inositol phosphate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrophosphatase activity	6
diadenosine polyphosphate catabolic process	2
transition metal ion binding	2
diphosphoinositol-polyphosphate diphosphatase activity	2
cellular anatomical structure	2
cell communication	1
signaling	1
nucleotide catabolic process	1
diadenosine polyphosphate metabolic process	1
inositol phosphate metabolic process	1
diphosphoinositol polyphosphate metabolic process	1
inositol phosphate catabolic process	1
RNA metabolic process	1
purine ribonucleotide catabolic process	1
metal ion binding	1
inositol diphosphate pentakisphosphate diphosphatase activity	1
inositol bisdiphosphate tetrakisphosphate diphosphatase activity	1
binding	1
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

1172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDT3	NUDT2	P50583	708
NUDT3	NUDT12	Q9BQG2	676
NUDT3	RAB17	Q9H0T7	670
NUDT3	NUDT16	Q96DE0	661
NUDT3	NUDT17	P0C025	657
NUDT3	TMEM160	Q9NX00	621
NUDT3	NUDT15	Q9NV35	599
NUDT3	QPCTL	Q9NXS2	592
NUDT3	NUDT22	Q9BRQ3	592
NUDT3	DNAJC27	Q9NZQ0	583
NUDT3	ZNF608	Q9ULD9	583
NUDT3	MTIF3	Q9H2K0	583
NUDT3	V9GXZ4	V9GXZ4	583
NUDT3	POC5	Q8NA72	580
NUDT3	NUDT5	Q9UKK9	578

IntAct

66 interactions, top by confidence:

A	B	Type	Score
LAMTOR2	LAMTOR5	psi-mi:“MI:0914”(association)	0.860
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640
NUDT3	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
ASB13	NUDT3	psi-mi:“MI:0915”(physical association)	0.550
RPLP1	NUDT3	psi-mi:“MI:0915”(physical association)	0.550
CRCP	NUDT3	psi-mi:“MI:0915”(physical association)	0.400
NUDT3	ALAS1	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	APEX1	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.370
VPS51	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	CCL11	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	CHCHD3	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	DBN1	psi-mi:“MI:0915”(physical association)	0.370
DDR1	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
DNAJA1	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
EEF1G	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	FXYD3	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	HES1	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	ITFG1	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	MAF1	psi-mi:“MI:0915”(physical association)	0.370
MCM5	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
MEX3B	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	NR2C1	psi-mi:“MI:0915”(physical association)	0.370
NUDT5	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
OAT	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	PDCD5	psi-mi:“MI:0915”(physical association)	0.370
NUDT3	PEX5	psi-mi:“MI:0915”(physical association)	0.370
PRKD3	NUDT3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (102): NUDT3 (Affinity Capture-RNA), NUDT3 (Affinity Capture-RNA), NUDT3 (Two-hybrid), NUDT3 (Affinity Capture-MS), NUDT3 (Affinity Capture-MS), NUDT3 (Affinity Capture-MS), ASB13 (Two-hybrid), RAB17 (Two-hybrid), RPL8 (Two-hybrid), RPLP1 (Two-hybrid), NUDT3 (Affinity Capture-RNA), NUDT3 (Affinity Capture-RNA), HSPA1A (Affinity Capture-MS), NUDT10 (Affinity Capture-MS), GM2A (Affinity Capture-MS)

ESM2 similar proteins: A0A024RBG1, A2VE79, A3KMI0, A7E320, B0R160, B6CHA3, F4JLK2, F6UA42, O22951, O45830, O59761, O95989, P0C027, P0C028, P32271, Q08C92, Q09790, Q566C7, Q58CW0, Q5RAF0, Q5RDX4, Q5U243, Q6NPD7, Q6P5D3, Q7TMI3, Q7TPK1, Q7YTB0, Q8BJM7, Q8CIG3, Q8L7W2, Q8NB78, Q8NFP7, Q8R2U6, Q8VDF2, Q8VHT6, Q91WU5, Q96G61, Q96PU4, Q96T88, Q99321

Diamond homologs: A0A024RBG1, A2VE79, O95989, P0C027, P0C028, P53370, P70563, P96590, Q09790, Q52K88, Q566C7, Q58CW0, Q5RAF0, Q8CH40, Q8NFP7, Q8R2U6, Q8VY81, Q93ZY7, Q96G61, Q99321, Q99MY2, Q9JI46, Q9LE73, Q9LHK1, Q9LQU5, Q9NZJ9, Q9ZU95, Q9RVK2, P32091, P59659, A0QUZ2, P9WIX6, P9WIX7, P9WIY2, P9WIY3, Q75UV1, D0N4K2, D0NSB3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUDT3	up-regulates	AKT2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1644 predictions. Top by Δscore:

Variant	Effect	Δscore
6:34288738:A:AC	donor_gain	1.0000
6:34288739:C:CC	donor_gain	1.0000
6:34293444:GGCTT:G	donor_loss	1.0000
6:34293445:GCTTA:G	donor_loss	1.0000
6:34293446:CTTAC:C	donor_loss	1.0000
6:34293447:TTA:T	donor_loss	1.0000
6:34293448:TA:T	donor_loss	1.0000
6:34293449:A:AC	donor_gain	1.0000
6:34293449:A:AT	donor_loss	1.0000
6:34293450:C:CC	donor_gain	1.0000
6:34293534:TT:T	acceptor_gain	1.0000
6:34293534:TTC:T	acceptor_loss	1.0000
6:34293536:C:CC	acceptor_gain	1.0000
6:34293544:C:CT	acceptor_gain	1.0000
6:34293545:A:T	acceptor_gain	1.0000
6:34311970:C:CA	donor_gain	1.0000
6:34341863:T:TA	donor_gain	1.0000
6:34392258:CCTCA:C	donor_loss	1.0000
6:34392259:CTCA:C	donor_loss	1.0000
6:34392260:TCA:T	donor_loss	1.0000
6:34392261:CACC:C	donor_loss	1.0000
6:34392262:A:C	donor_loss	1.0000
6:34392262:ACCT:A	donor_gain	1.0000
6:34392263:C:CG	donor_loss	1.0000
6:34392263:CCTC:C	donor_gain	1.0000
6:34392265:T:TA	donor_gain	1.0000
6:34392268:T:TA	donor_gain	1.0000
6:34288708:T:TA	donor_gain	0.9900
6:34288930:TCCT:T	acceptor_loss	0.9900
6:34288931:CCTG:C	acceptor_loss	0.9900

AlphaMissense

1115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:34288917:A:G	W119R	1.000
6:34288917:A:T	W119R	1.000
6:34288927:C:A	R115S	1.000
6:34288927:C:G	R115S	1.000
6:34288928:C:A	R115M	1.000
6:34288928:C:G	R115T	1.000
6:34295681:C:T	G72E	1.000
6:34341878:C:G	R65P	1.000
6:34341879:G:T	R65S	1.000
6:34341923:C:T	G50E	1.000
6:34341926:G:T	P49H	1.000
6:34341929:A:T	V48D	1.000
6:34341936:A:G	W46R	1.000
6:34341936:A:T	W46R	1.000
6:34341965:A:G	L36P	1.000
6:34341968:A:G	L35P	1.000
6:34392288:A:C	C25W	1.000
6:34288886:A:G	L129P	0.999
6:34288915:C:A	W119C	0.999
6:34288915:C:G	W119C	0.999
6:34288921:C:A	R117S	0.999
6:34288921:C:G	R117S	0.999
6:34293466:C:G	D109H	0.999
6:34293470:C:A	W107C	0.999
6:34293470:C:G	W107C	0.999
6:34293472:A:G	W107R	0.999
6:34293472:A:T	W107R	0.999
6:34293498:A:G	L98P	0.999
6:34293507:A:T	V95D	0.999
6:34293515:C:A	R92S	0.999

dbSNP variants (sampled 300 via entrez): RS1000010018 (6:34329049 G>A), RS1000045434 (6:34388209 A>G), RS1000059920 (6:34368519 A>G,T), RS1000096375 (6:34341028 A>G), RS1000097815 (6:34294657 C>T), RS1000099505 (6:34300597 A>G), RS1000113391 (6:34323583 G>T), RS1000113865 (6:34281614 C>T), RS1000149795 (6:34365196 A>G,T), RS1000164264 (6:34346861 T>A), RS1000166389 (6:34304873 T>C), RS1000201293 (6:34298360 A>G), RS1000216255 (6:34346701 C>T), RS1000310729 (6:34294554 T>C), RS1000318554 (6:34287942 TA>T,TAA)

Disease associations

OMIM: gene MIM:609228 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000522_11	Height	2.000000e-08
GCST000830_21	Body mass index	3.000000e-08
GCST002702_56	Height	2.000000e-30
GCST004066_33	Hip circumference	4.000000e-06
GCST004066_85	Hip circumference	3.000000e-08
GCST006061_128	Atrial fibrillation	4.000000e-08
GCST006630_4	Diastolic blood pressure	3.000000e-16
GCST007294_103	Body fat distribution (trunk fat ratio)	3.000000e-11
GCST007295_123	Body fat distribution (leg fat ratio)	1.000000e-12
GCST007344_99	Estimated glomerular filtration rate	2.000000e-10
GCST008839_202	Height	7.000000e-14
GCST008839_266	Height	8.000000e-24
GCST009764_21	Body mass index	1.000000e-07
GCST010002_50	Refractive error	4.000000e-34
GCST012226_466	Waist circumference adjusted for body mass index	5.000000e-08
GCST012226_471	Waist circumference adjusted for body mass index	6.000000e-13
GCST012227_941	Hip circumference adjusted for BMI	8.000000e-16
GCST012227_944	Hip circumference adjusted for BMI	7.000000e-09
GCST012227_945	Hip circumference adjusted for BMI	6.000000e-09
GCST012228_266	Waist-hip index	1.000000e-11
GCST012230_456	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90000032_8	Myeloproliferative neoplasms	3.000000e-09
GCST90020024_824	A body shape index	1.000000e-15
GCST90020024_825	A body shape index	2.000000e-35
GCST90020025_718	Waist-to-hip ratio adjusted for BMI	1.000000e-17
GCST90020027_1087	Waist-hip index	3.000000e-19
GCST90020027_1138	Waist-hip index	2.000000e-42
GCST90020028_665	Hip circumference adjusted for BMI	2.000000e-18
GCST90020028_668	Hip circumference adjusted for BMI	3.000000e-10
GCST90020029_1538	Waist circumference adjusted for body mass index	9.000000e-47

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0004341	body fat distribution
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004251	myeloproliferative disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295689 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	3
sodium arsenite	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
indolo(3,2-b)carbazole	decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 2 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4259501	Binding	Stabilization of N-terminal His-tagged DIPP1 (unknown origin) expressed in Escherichia coli assessed as increase in melting temperature at 0.1 mM by SYPRO orange dye based DSF method	A synthetic diphosphoinositol phosphate analogue of inositol trisphosphate. — Medchemcomm
CHEMBL4259506	ADMET	Substrate activity at N-terminal His-tagged DIPP1 (unknown origin) expressed in Escherichia coli assessed as enzyme-mediated test compound metabolism after 20 mins in presence of Mg2+ by malachite green dye based assay	A synthetic diphosphoinositol phosphate analogue of inositol trisphosphate. — Medchemcomm

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1ZC	Abcam HeLa NUDT3 KO	Cancer cell line	Female
CVCL_TB40	HAP1 NUDT3 (-) 1	Cancer cell line	Male
CVCL_TB41	HAP1 NUDT3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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