NUDT5

Summary

NUDT5 (nudix hydrolase 5, HGNC:8052) is a protein-coding gene on chromosome 10p14, encoding ADP-sugar pyrophosphatase (Q9UKK9). Enzyme that can either act as an ADP-sugar pyrophosphatase in absence of diphosphate or catalyze the synthesis of ATP in presence of diphosphate.

This gene belongs to the Nudix (nucleoside diphosphate linked moiety X) hydrolase superfamily. The encoded enzyme catalyzes the hydrolysis of modified nucleoside diphosphates, including ADP-ribose (ADPR) and 8-oxoGua-containing 8-oxo-dADP and 8-oxo-dGDP. Protein-bound ADP ribose can be hazardous to the cell because it can modify some amino acid residues, resulting in the inhibition of ATP-activated potassium channels. 8-oxoGua is an oxidized form of guanine that can potentially alter genetic information by pairing with adenine and cytosine in RNA. Presence of 8-oxoGua in RNA results in formation of abnormal proteins due to translational errors.

Source: NCBI Gene 11164 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8052
Approved symbol	NUDT5
Name	nudix hydrolase 5
Location	10p14
Locus type	gene with protein product
Status	Approved
Aliases	hYSAH1, YSA1H
Ensembl gene	ENSG00000165609
Ensembl biotype	protein_coding
OMIM	609230
Entrez	11164

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000378927, ENST00000378937, ENST00000378940, ENST00000378952, ENST00000444732, ENST00000476462, ENST00000491614, ENST00000498825, ENST00000905392, ENST00000905393, ENST00000905394, ENST00000905395

RefSeq mRNA: 3 — MANE Select: NM_014142 NM_001321647, NM_001321648, NM_014142

CCDS: CCDS7089

Canonical transcript exons

ENST00000491614 — 10 exons

Exon	Start	End
ENSE00001479440	12195770	12195891
ENSE00001955244	12165330	12167811
ENSE00003493132	12179083	12179132
ENSE00003526952	12170900	12170908
ENSE00003572239	12172765	12172866
ENSE00003583709	12177793	12177900
ENSE00003623523	12184889	12184956
ENSE00003625590	12186229	12186332
ENSE00003665700	12170717	12170770
ENSE00003692670	12173718	12173813

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 95.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.8628 / max 709.2069, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108269	53.5616	1820
108268	3.0181	1464
108270	2.2831	1169

Top tissues by expression

256 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	95.10	gold quality
right lobe of liver	UBERON:0001114	95.08	gold quality
ganglionic eminence	UBERON:0004023	94.71	gold quality
rectum	UBERON:0001052	94.69	gold quality
stromal cell of endometrium	CL:0002255	94.67	gold quality
gingival epithelium	UBERON:0001949	94.59	gold quality
islet of Langerhans	UBERON:0000006	94.13	gold quality
ileal mucosa	UBERON:0000331	94.10	gold quality
ventricular zone	UBERON:0003053	93.99	gold quality
gingiva	UBERON:0001828	93.91	gold quality
adenohypophysis	UBERON:0002196	93.91	gold quality
liver	UBERON:0002107	93.78	gold quality
mucosa of transverse colon	UBERON:0004991	93.33	gold quality
esophagus mucosa	UBERON:0002469	93.26	gold quality
pituitary gland	UBERON:0000007	93.23	gold quality
left adrenal gland	UBERON:0001234	92.98	gold quality
skin of abdomen	UBERON:0001416	92.97	gold quality
blood	UBERON:0000178	92.95	gold quality
right adrenal gland	UBERON:0001233	92.94	gold quality
omental fat pad	UBERON:0010414	92.93	gold quality
peritoneum	UBERON:0002358	92.90	gold quality
left adrenal gland cortex	UBERON:0035825	92.85	gold quality
right adrenal gland cortex	UBERON:0035827	92.73	gold quality
upper arm skin	UBERON:0004263	92.72	gold quality
right lobe of thyroid gland	UBERON:0001119	92.71	gold quality
vermiform appendix	UBERON:0001154	92.62	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.59	gold quality
right lung	UBERON:0002167	92.58	gold quality
kidney epithelium	UBERON:0004819	92.46	gold quality
metanephros	UBERON:0000081	92.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.51
E-CURD-112	yes	13.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting NUDT5, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-378G	99.71	64.90	1106

Literature-anchored findings (GeneRIF, showing 15)

• degrades 8-oxo-dGDP to 8-oxo-dGMP, an unusable form for DNA synthesis, and promotes the cleavage of 8-oxo-dGTP by MTH1 to yield 8-oxo-dGMP also (PMID:12717453)
• Results report the crystal structure of hNUDT5 in complex with a non-hydrolyzable ADPR analogue, alpha,beta-methyleneadenosine diphosphoribose, and three Mg(2+) ions representing the transition state of the enzyme during catalysis. (PMID:18462755)
• NUDT5 protein eliminates various oxidized deoxyribonucleoside diphosphates from the nucleotide pool and prevents their toxic effects. (PMID:19699693)
• human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP. (PMID:20144704)
• The human NUDT5, which has an intrinsic activity to cleave ADP sugars to AMP and sugar phosphate, possesses the ability to degrade 8-oxo-dGDP to the monophosphate. (PMID:21389046)
• The broad substrate specificity of hNUDT5 is achieved by a diversity of not only substrate recognition, but also hydrolysis mechanisms. (PMID:21768126)
• Results suggest that the NUDT5 protein may play significant roles in regulating the G1-S transition in HeLa cells. (PMID:22200976)
• The NUDT5 protein could play significant roles in the prevention of RNA oxidation and survival in human fibroblast cells. (PMID:23581889)
• In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. (PMID:27257257)
• Data suggest that targeting nudix hydrolase 5 (NUDT5) may represent a promising new therapeutic approach for breast cancer treatment. (PMID:29343827)
• The high expression of MTH1 and NUDT5 promotes tumor metastasis and indicates a poor prognosis in patients with non-small-cell lung cancer. (PMID:33096144)
• The high expression of NUDT5 indicates poor prognosis of breast cancer by modulating AKT / Cyclin D signaling. (PMID:33571243)
• Silencing of Nudix type 5 represses proliferation and invasion and enhances chemosensitivity of gastric carcinoma cells by affecting the AKT/GSK-3beta/beta-catenin pathway. (PMID:35247377)
• NUDT5-Determines the fate of head and neck squamous cell carcinoma cells under endoplasmic reticulum stress by catalyzing nuclear ATP production to promote DNA repair. (PMID:37156197)
• The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth. (PMID:38317231)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nudt5	ENSDARG00000078073
mus_musculus	Nudt5	ENSMUSG00000025817
rattus_norvegicus	Nudt5	ENSRNOG00000017741
caenorhabditis_elegans		WBGENE00003579

Paralogs (1): NUDT14 (ENSG00000183828)

Protein

Protein identifiers

ADP-sugar pyrophosphatase — Q9UKK9 (reviewed: Q9UKK9)

Alternative names: 8-oxo-dGDP phosphatase, Nuclear ATP-synthesis protein NUDIX5, Nucleoside diphosphate-linked moiety X motif 5, YSA1H

All UniProt accessions (6): A6NCQ0, A6NFX8, A6NJU6, C9JYY9, Q9UKK9, H0YEY4

UniProt curated annotations — full annotation on UniProt →

Function. Enzyme that can either act as an ADP-sugar pyrophosphatase in absence of diphosphate or catalyze the synthesis of ATP in presence of diphosphate. In absence of diphosphate, hydrolyzes with similar activities various modified nucleoside diphosphates such as ADP-ribose, ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP. Can also hydrolyze other nucleotide sugars with low activity. In presence of diphosphate, mediates the synthesis of ATP in the nucleus by catalyzing the conversion of ADP-ribose to ATP and ribose 5-phosphate. Nuclear ATP synthesis takes place when dephosphorylated at Thr-45. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. In vitro, it has decapping activity on 11-mer RNA capped with uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) by hydrolyzing the pyrophosphate bridge of the sugar cap. Does not play a role in U8 snoRNA decapping. Binds U8 snoRNA.

Subunit / interactions. Homodimer. Interacts with PARG.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Most abundant in liver.

Post-translational modifications. Phosphorylation at Thr-45 is required for homodimer stability; dephosphorylation results in destabilization of the homodimer. Dephosphorylation at Thr-45 promotes the ATP-synthesis activity.

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

Induction. Overexpressed in cancer patients with a poor outcome.

Similarity. Belongs to the Nudix hydrolase family.

RefSeq proteins (3): NP_001308576, NP_001308577, NP_054861* (*=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
IPR020476	Nudix_hydrolase	Domain

Pfam: PF00293

Enzyme classification (BRENDA):

• EC 2.7.7.96 — ADP-D-ribose pyrophosphorylase (BRENDA: 1 organisms, 6 substrates, 34 inhibitors, 0 Km, 0 kcat entries)
• EC 3.6.1.13 — ADP-ribose diphosphatase (BRENDA: 21 organisms, 113 substrates, 38 inhibitors, 159 Km, 142 kcat entries)
• EC 3.6.1.58 — 8-oxo-dGDP phosphatase (BRENDA: 2 organisms, 30 substrates, 3 inhibitors, 14 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ADP-RIBOSE	0.0019–2.1	55
ADPRIBOSE	0.0004–0.37	23
ADP-D-RIBOSE	0.0209–0.3213	21
2’,3’-CAMP	0.76–7.6	16
CDP-CHOLINE	0.35–43	16
8-OXO-DGDP	0.0021–0.77	5
CADP-RIBOSE	0.19–0.78	4
8-OXO-DGDP	0.0035–0.0038	2
ADP	2.65–19	2
ADP-MANNOSE	0.083–0.154	2
CDP-ETHANOLAMINE	3.9–31	2
CDP-GLYCEROL	2–6.3	2
FAD	0.3–0.33	2
8-OXO-GDP	0.0049–0.0117	2
DGDP	0.0076–7.1	2

Catalyzed reactions (Rhea), 4 shown:

• ADP-D-ribose + H2O = D-ribose 5-phosphate + AMP + 2 H(+) (RHEA:10412)
• 8-oxo-dGDP + H2O = 8-oxo-dGMP + phosphate + H(+) (RHEA:32063)
• D-ribose 5-phosphate + ATP + H(+) = ADP-D-ribose + diphosphate (RHEA:50248)
• a 5’-end N-acetyl-alpha-D-glucosamine-diphospho-uridyl-ribonucleoside in mRNA + H2O = a 5’-end phospho-ribonucleoside in mRNA + UDP-N-acetyl-alpha-D-glucosamine + H(+) (RHEA:82603)

UniProt features (56 total): binding site 12, strand 12, mutagenesis site 10, modified residue 7, helix 6, turn 3, chain 1, domain 1, short sequence motif 1, cross-link 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

69 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5QK0	X-RAY DIFFRACTION	1.44
5QJC	X-RAY DIFFRACTION	1.47
5QK1	X-RAY DIFFRACTION	1.49
5QJP	X-RAY DIFFRACTION	1.5
5QK6	X-RAY DIFFRACTION	1.51
5QJZ	X-RAY DIFFRACTION	1.52
5QJQ	X-RAY DIFFRACTION	1.55
5QKA	X-RAY DIFFRACTION	1.55
5QTR	X-RAY DIFFRACTION	1.55
5QJ7	X-RAY DIFFRACTION	1.56
5QK9	X-RAY DIFFRACTION	1.56
5QJG	X-RAY DIFFRACTION	1.57
5QJW	X-RAY DIFFRACTION	1.57
5QJS	X-RAY DIFFRACTION	1.58
5QKB	X-RAY DIFFRACTION	1.58
5QJD	X-RAY DIFFRACTION	1.61
5QJV	X-RAY DIFFRACTION	1.61
5QJR	X-RAY DIFFRACTION	1.62
5QJT	X-RAY DIFFRACTION	1.62
5QK4	X-RAY DIFFRACTION	1.62
5QJF	X-RAY DIFFRACTION	1.63
5QK5	X-RAY DIFFRACTION	1.63
5QJA	X-RAY DIFFRACTION	1.64
5QJ6	X-RAY DIFFRACTION	1.65
5QJK	X-RAY DIFFRACTION	1.65
5QK2	X-RAY DIFFRACTION	1.65
5QJB	X-RAY DIFFRACTION	1.66
5QJL	X-RAY DIFFRACTION	1.66
5QK7	X-RAY DIFFRACTION	1.66
5QTO	X-RAY DIFFRACTION	1.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKK9-F1	92.34	0.84

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 (12): 112; 116; 116; 133 (in other chain); 166; 28 (in other chain); 46–47; 51; 84 (in other chain); 96; 98 (in other chain); 112

Post-translational modifications (8): 1, 3, 10, 45, 74, 210, 218, 42

Mutagenesis-validated functional residues (10):

Position	Phenotype
28	reduces affinity for substrate about 8-fold. strongly reduced catalytic activity and strongly reduced affinity for subst
45	impaired phosphorylation; generates atp in the presence of diphosphate.
45	phosphomimetic mutant; unable to generate atp in the presence of diphosphate.
46	reduces affinity for substrate about 6-fold. strongly reduced catalytic activity and strongly reduced affinity for subst
51	reduces affinity for substrate about 15-fold and reduces catalytic rate about 17-fold.
84	reduces affinity for substrate about 5-fold and reduces catalytic rate 67-fold.
98	reduces affinity for substrate about 6-fold.
112	catalytic inactive mutant for both adp-sugar pyrophosphatase and nuclear atp-synthesis activities. reduces catalytic rat
116	reduces catalytic rate 2000-fold.
166	reduces catalytic rate 120-fold.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 193 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, KEGG_PURINE_METABOLISM, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS

GO Biological Process (9): chromatin remodeling (GO:0006338), nucleoside phosphate metabolic process (GO:0006753), nucleotide metabolic process (GO:0009117), ribonucleoside diphosphate catabolic process (GO:0009191), D-ribose catabolic process (GO:0019303), ribose phosphate metabolic process (GO:0019693), nucleobase-containing small molecule metabolic process (GO:0055086), ATP generation from poly-ADP-D-ribose (GO:1990966), nucleobase-containing compound metabolic process (GO:0006139)

GO Molecular Function (14): magnesium ion binding (GO:0000287), nucleotidyltransferase activity (GO:0016779), ADP-sugar pyrophosphatase activity (GO:0019144), snoRNA binding (GO:0030515), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), 8-oxo-dGDP phosphatase activity (GO:0044715), ADP-ribose diphosphatase activity (GO:0047631), RNA binding (GO:0003723), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787), nucleoside diphosphate phosphatase activity (GO:0017110), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), extracellular exosome (GO:0070062)

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
pyrophosphatase activity	3
organophosphate metabolic process	2
catalytic activity	2
chromatin organization	1
nucleobase-containing small molecule metabolic process	1
nucleoside phosphate metabolic process	1
nucleoside diphosphate catabolic process	1
ribonucleoside diphosphate metabolic process	1
D-ribose metabolic process	1
pentose catabolic process	1
carbohydrate derivative metabolic process	1
nucleobase-containing compound metabolic process	1
small molecule metabolic process	1
macromolecule metabolic process	1
ATP metabolic process	1
primary metabolic process	1
metal ion binding	1
transferase activity, transferring phosphorus-containing groups	1
RNA binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside diphosphate phosphatase activity	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDT5	NUDT18	Q6ZVK8	811
NUDT5	NUDT9	Q9BW91	794
NUDT5	NUDT15	Q9NV35	792
NUDT5	NUDT14	O95848	775
NUDT5	NUDT1	P36639	761
NUDT5	PARG	Q86W56	756
NUDT5	NUDT12	Q9BQG2	736
NUDT5	NUDT2	P50583	725
NUDT5	NUDT22	Q9BRQ3	718
NUDT5	NUDT17	P0C025	710
NUDT5	NUDT3	O95989	578
NUDT5	NUDT4B	A0A024RBG1	577
NUDT5	NUDT16	Q96DE0	574
NUDT5	ADPRS	Q9NX46	570
NUDT5	NUDT8	Q8WV74	561

IntAct

63 interactions, top by confidence:

A	B	Type	Score
PPAT	NUDT5	psi-mi:“MI:0915”(physical association)	0.640
NUDT5	NUDT5	psi-mi:“MI:0915”(physical association)	0.560
COX5B	NUDT5	psi-mi:“MI:0915”(physical association)	0.560
GORASP2	NUDT5	psi-mi:“MI:0915”(physical association)	0.560
Mad2l1	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
PYCR1	PYCR3	psi-mi:“MI:0914”(association)	0.530
NHERF2	ACTN4	psi-mi:“MI:0914”(association)	0.510
HSPB9	NUDT5	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	NUDT5	psi-mi:“MI:0915”(physical association)	0.370
NUDT5	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
SKA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
PYCR2	MYO1F	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
DUSP14	AP3B1	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
C3orf62	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
	KIF5C	psi-mi:“MI:0914”(association)	0.350
NUTM2F	IRF6	psi-mi:“MI:0914”(association)	0.350
SUZ12	TNPO2	psi-mi:“MI:0914”(association)	0.350
HLA-A	AIP	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
NUDT5	FLNB	psi-mi:“MI:0914”(association)	0.350

BioGRID (104): NUDT5 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Proximity Label-MS), NUDT5 (Proximity Label-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Proximity Label-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), SLC9A3R2 (Affinity Capture-MS), YAP1 (Affinity Capture-MS)

ESM2 similar proteins: A3KPF2, B9KHF1, G5EDZ2, M4I1C6, O14353, O61902, O93937, O94632, O94634, P05165, P0C024, P0DTA4, P13420, P14882, P41888, P48445, P91148, Q01976, Q06490, Q19427, Q22943, Q23236, Q29RH3, Q2M197, Q42777, Q4R7L8, Q4WM52, Q54EW2, Q5PBX6, Q5RCY2, Q5RD76, Q6AY63, Q6NPD7, Q7S8A6, Q86X67, Q8LET2, Q91ZA3, Q94B74, Q96RQ3, Q99P30

Diamond homologs: O45830, O61902, P45799, P54570, P96590, Q01976, Q58549, Q5RCY2, Q6AY63, Q8KP10, Q9JKX6, Q9P791, Q9UKK9, A0K4B3, A0KG29, A1SS92, A1TTD1, A1TYU2, A1V0N7, A1VK87, A1VYU1, A1W4B2, A1WKI2, A2S5R4, A2SD39, A3MR94, A3NDS3, A3NZI7, A4G8R1, A4IWB3, A4JBC1, A4SIW4, A5UDH3, A5UI45, A6Q441, A6T2D2, A6VMA3, A7H3U9, A7MXK7, A7NEA4

SIGNOR signaling

0 interactions.

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	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2107 predictions. Top by Δscore:

Variant	Effect	Δscore
10:12167812:C:CC	acceptor_gain	1.0000
10:12172761:ATACC:A	donor_loss	1.0000
10:12172762:TA:T	donor_loss	1.0000
10:12172763:A:AC	donor_gain	1.0000
10:12172764:C:A	donor_loss	1.0000
10:12172764:C:CC	donor_gain	1.0000
10:12172764:CCTGG:C	donor_gain	1.0000
10:12172862:GACCG:G	acceptor_gain	1.0000
10:12172863:ACCG:A	acceptor_gain	1.0000
10:12172864:CCG:C	acceptor_gain	1.0000
10:12172864:CCGC:C	acceptor_gain	1.0000
10:12172865:CG:C	acceptor_gain	1.0000
10:12172865:CGCTG:C	acceptor_gain	1.0000
10:12172866:GCT:G	acceptor_loss	1.0000
10:12172867:C:CC	acceptor_gain	1.0000
10:12172867:C:CG	acceptor_loss	1.0000
10:12172868:T:C	acceptor_loss	1.0000
10:12177788:CTCA:C	donor_loss	1.0000
10:12177789:TCA:T	donor_loss	1.0000
10:12177901:CTGT:C	acceptor_loss	1.0000
10:12178572:T:TA	donor_gain	1.0000
10:12178573:C:A	donor_gain	1.0000
10:12178987:T:TA	donor_gain	1.0000
10:12179046:T:TA	donor_gain	1.0000
10:12186225:ATAC:A	donor_loss	1.0000
10:12186227:A:AT	donor_loss	1.0000
10:12186227:ACCT:A	donor_gain	1.0000
10:12186228:C:CA	donor_loss	1.0000
10:12186228:CCTC:C	donor_gain	1.0000
10:12186230:T:TA	donor_gain	1.0000

AlphaMissense

1420 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:12173765:A:G	L113P	0.997
10:12173777:G:T	A109D	0.997
10:12173771:C:G	R111P	0.996
10:12177798:G:T	P95H	0.996
10:12177833:G:C	F83L	0.996
10:12177833:G:T	F83L	0.996
10:12177835:A:G	F83L	0.996
10:12177849:A:T	V78D	0.996
10:12177832:G:C	R84G	0.995
10:12179113:G:T	R51S	0.995
10:12167760:G:T	A201D	0.994
10:12167772:A:T	V197D	0.994
10:12172809:A:T	I148N	0.994
10:12177831:C:G	R84P	0.994
10:12179126:C:A	W46C	0.994
10:12179126:C:G	W46C	0.994
10:12179128:A:G	W46R	0.994
10:12179128:A:T	W46R	0.994
10:12172815:A:T	V146D	0.993
10:12173765:A:T	L113H	0.993
10:12177809:G:C	C91W	0.993
10:12177879:A:G	L68P	0.993
10:12167764:A:C	Y200D	0.992
10:12173748:A:C	Y119D	0.992
10:12177798:G:C	P95R	0.992
10:12170722:A:T	L182H	0.991
10:12170734:A:G	L178P	0.991
10:12173778:C:G	A109P	0.991
10:12177796:C:G	A96P	0.991
10:12177846:A:G	L79P	0.991

dbSNP variants (sampled 300 via entrez): RS1000109990 (10:12186150 T>C), RS1000148298 (10:12191632 T>C), RS1000222692 (10:12179203 A>G), RS1000234817 (10:12194378 T>C), RS1000276893 (10:12196593 T>C), RS1000329986 (10:12173794 T>C), RS1000336912 (10:12180607 C>T), RS1000360604 (10:12166007 G>A), RS1000443631 (10:12168303 C>A,T), RS1000458104 (10:12191323 C>T), RS1000501699 (10:12171653 A>G), RS1000558226 (10:12177696 C>T), RS1000577314 (10:12178923 T>A,C), RS1000784187 (10:12174028 A>G), RS1000940170 (10:12186541 A>C)

Disease associations

OMIM: gene MIM:609230 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011320_22	Type 2 diabetes or prostate cancer (pleiotropy)	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105713 (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: 8,954 (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
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL4072833	EVOBRUTINIB	3	960

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

ChEMBL bioactivities

15 potent at pChembl≥5 of 18 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	EC50	2.5	nM	CHEMBL5557167
7.54	IC50	29	nM	CHEMBL5557167
6.70	Kd	200	nM	IBRUTINIB
6.60	Kd	250	nM	CHEMBL5527860
6.57	IC50	270	nM	CHEMBL5527860
6.31	IC50	487	nM	CHEMBL5549952
6.08	IC50	837	nM	IBRUTINIB
6.08	IC50	830	nM	IBRUTINIB
5.97	EC50	1080	nM	CHEMBL5527860
5.91	EC50	1230	nM	IBRUTINIB
5.69	IC50	2040	nM	CHEMBL1242204
5.44	Kd	3617	nM	CHEMBL3752910
5.42	ED50	3757	nM	CHEMBL3752910
5.11	Kd	7684	nM	CHEMBL5653589
5.10	ED50	7983	nM	CHEMBL5653589

PubChem BioAssay actives

12 with measured affinity, of 28 total; 7 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
7-[[5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl]methyl]-1,3-dimethyl-8-piperazin-1-ylpurine-2,6-dione	2070374: Antagonist activity at N-terminal his6-tagged human recombinant NUDT5 (1 to 208 residues) expressed in Escherichia coli Rosetta (DE3) expressed in HEK293 cells incubated for 2 hrs by nanoBRET assay	ec50	0.0025	uM
Ibrutinib	2070373: Binding affinity to N-terminal his6-tagged human recombinant NUDT5 (1 to 208 residues) expressed in Escherichia coli Rosetta (DE3) assessed as dissociation constant by SPR analysis	kd	0.2000	uM
1-(1-methylpiperidin-4-yl)-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-amine	2070373: Binding affinity to N-terminal his6-tagged human recombinant NUDT5 (1 to 208 residues) expressed in Escherichia coli Rosetta (DE3) assessed as dissociation constant by SPR analysis	kd	0.2500	uM
1-methyl-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-amine	2070371: Antagonist activity at N-terminal his6-tagged human recombinant NUDT5 (1 to 208 residues) expressed in Escherichia coli Rosetta (DE3) using ADP as substrate incubated for 1 hr by luminescence based microplate reader analysis	ic50	0.4870	uM
3-(4-phenoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine	2070371: Antagonist activity at N-terminal his6-tagged human recombinant NUDT5 (1 to 208 residues) expressed in Escherichia coli Rosetta (DE3) using ADP as substrate incubated for 1 hr by luminescence based microplate reader analysis	ic50	2.0400	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148899: Binding affinity to human NUDT5 incubated for 45 mins by Kinobead based pull down assay	kd	3.6168	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148899: Binding affinity to human NUDT5 incubated for 45 mins by Kinobead based pull down assay	kd	7.6845	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
cupric chloride	increases expression	1
beta-methylcholine	affects expression	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
pyrachlostrobin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	decreases expression	1
Cisplatin	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 8 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4008387	Binding	Inhibition of human His-tagged NUDT5 expressed in bacterial expression system in presence of ADP after 1 hr by malachite green reagent based assay	Identification of Triazolothiadiazoles as Potent Inhibitors of the dCTP Pyrophosphatase 1. — J Med Chem
CHEMBL5723177	Functional	Affinity Biochemical interaction: (MG assay) EUB0002332a NUDT5	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3D0	Abcam HEK293T NUDT5 KO	Transformed cell line	Female
CVCL_E2F5	HAP1 NUDT5 (-) 1	Cancer cell line	Male
CVCL_E2F6	HAP1 NUDT5 (-) 2	Cancer cell line	Male
CVCL_E2F7	HAP1 NUDT5 (-) 3	Cancer cell line	Male
CVCL_E2F8	HAP1 NUDT5 (-) 4	Cancer cell line	Male
CVCL_E2F9	HAP1 NUDT5 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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