NUDT2

Summary

NUDT2 (nudix hydrolase 2, HGNC:8049) is a protein-coding gene on chromosome 9p13.3, encoding Bis(5’-nucleosyl)-tetraphosphatase [asymmetrical] (P50583). Catalyzes the asymmetric hydrolysis of diadenosine 5’,5’’’-P1,P4-tetraphosphate (Ap4A) to yield AMP and ATP.

This gene encodes a member of the MutT family of nucleotide pyrophosphatases, a subset of the larger NUDIX hydrolase family. The gene product possesses a modification of the MutT sequence motif found in certain nucleotide pyrophosphatases. The enzyme asymmetrically hydrolyzes Ap4A to yield AMP and ATP and is responsible for maintaining the intracellular level of the dinucleotide Ap4A, the function of which has yet to be established. This gene may be a candidate tumor suppressor gene. Alternative splicing has been observed at this locus and four transcript variants, all encoding the same protein, have been identified.

Source: NCBI Gene 318 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with or without peripheral neuropathy (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 28 total — 2 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes
• MANE Select transcript: NM_001161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8049
Approved symbol	NUDT2
Name	nudix hydrolase 2
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164978
Ensembl biotype	protein_coding
OMIM	602852
Entrez	318

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000346365, ENST00000379155, ENST00000379158, ENST00000618590, ENST00000892438, ENST00000892439, ENST00000892440, ENST00000892441, ENST00000892442, ENST00000892443, ENST00000892444, ENST00000892445, ENST00000892446, ENST00000929626, ENST00000929627, ENST00000929628, ENST00000969606, ENST00000969607

RefSeq mRNA: 4 — MANE Select: NM_001161 NM_001161, NM_001244390, NM_147172, NM_147173

CCDS: CCDS6552

Canonical transcript exons

ENST00000379158 — 5 exons

Exon	Start	End
ENSE00001089099	34339024	34339166
ENSE00001259389	34336229	34336341
ENSE00001357794	34338713	34338847
ENSE00003718111	34343124	34343699
ENSE00003850897	34329569	34329599

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 92.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3994 / max 71.5713, expressed in 1786 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96509	12.7561	1780
96510	1.0810	716
96508	0.5623	346

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	92.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.91	gold quality
islet of Langerhans	UBERON:0000006	91.39	gold quality
apex of heart	UBERON:0002098	90.90	gold quality
right adrenal gland cortex	UBERON:0035827	90.80	gold quality
right adrenal gland	UBERON:0001233	90.65	gold quality
body of pancreas	UBERON:0001150	90.55	gold quality
left adrenal gland cortex	UBERON:0035825	89.97	gold quality
left adrenal gland	UBERON:0001234	89.94	gold quality
prefrontal cortex	UBERON:0000451	89.87	gold quality
nucleus accumbens	UBERON:0001882	89.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.80	gold quality
granulocyte	CL:0000094	89.76	gold quality
spinal cord	UBERON:0002240	89.71	gold quality
anterior cingulate cortex	UBERON:0009835	89.62	gold quality
cingulate cortex	UBERON:0003027	89.51	gold quality
adenohypophysis	UBERON:0002196	89.41	gold quality
pancreas	UBERON:0001264	89.40	gold quality
left ovary	UBERON:0002119	89.39	gold quality
amygdala	UBERON:0001876	89.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.36	gold quality
mucosa of stomach	UBERON:0001199	89.32	gold quality
putamen	UBERON:0001874	89.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.09	gold quality
lower esophagus	UBERON:0013473	89.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.05	gold quality
adrenal cortex	UBERON:0001235	88.80	gold quality
right frontal lobe	UBERON:0002810	88.77	gold quality
mucosa of transverse colon	UBERON:0004991	88.77	gold quality
caudate nucleus	UBERON:0001873	88.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.49
E-HCAD-5	no	2.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting NUDT2, 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-340-5P	100.00	72.50	4437
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429

Literature-anchored findings (GeneRIF, showing 10)

• crystallographic structure and substrate-binding mechanism of Ap4A hydrolase (PMID:15596429)
• NMR resonance assignments (PMID:15772762)
• In this study the authors present data demonstrating that the SARS-CoV 7a protein interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). (PMID:20144233)
• High NUDT2 is associated with breast carcinoma. (PMID:20533549)
• This paper presents the crystal structure of wild-type and E58A mutant human Ap4A hydrolase. (PMID:23384440)
• Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. (PMID:27144453)
• NUDT2 is a novel complex formation enhancing factor regulating mTORC1-Rag GTPase signaling that is crucial for cell growth control. (PMID:28089905)
• NUDT2 initiates viral RNA degradation by removal of 5’-phosphates. (PMID:34824277)
• Role of Nudt2 in Anchorage-Independent Growth and Cell Migration of Human Melanoma. (PMID:37445693)
• Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease. (PMID:38141063)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nudt2	ENSDARG00000058728
mus_musculus	Nudt2	ENSMUSG00000028443
rattus_norvegicus	Nudt2	ENSRNOG00000013110
caenorhabditis_elegans	ndx-4	WBGENE00003581

Protein

Protein identifiers

Bis(5’-nucleosyl)-tetraphosphatase [asymmetrical] — P50583 (reviewed: P50583)

Alternative names: Diadenosine 5’,5’’’-P1,P4-tetraphosphate asymmetrical hydrolase, Nucleoside diphosphate-linked moiety X motif 2

All UniProt accessions (1): P50583

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the asymmetric hydrolysis of diadenosine 5’,5’’’-P1,P4-tetraphosphate (Ap4A) to yield AMP and ATP. Exhibits decapping activity towards FAD-capped RNAs and dpCoA-capped RNAs in vitro.

Disease relevance. Intellectual developmental disorder with or without peripheral neuropathy (IDDPN) [MIM:619844] An autosomal recessive disorder characterized by global developmental delay appearing in infancy or early childhood, intellectual disability, and progressive sensorimotor neuropathy with associated distal weakness. Affected individuals have hypotonia and delayed walking with an unsteady gait and frequent falls. Additional features may include dysarthria and subtle facial dysmorpism. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Divalent metal ions.

Similarity. Belongs to the Nudix hydrolase family.

RefSeq proteins (4): NP_001152, NP_001231319, NP_671701, NP_671702 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000086	NUDIX_hydrolase_dom	Domain
IPR003565	Tetra_PHTase	Family
IPR015797	NUDIX_hydrolase-like_dom_sf	Homologous_superfamily
IPR020084	NUDIX_hydrolase_CS	Conserved_site
IPR051325	Nudix_hydrolase_domain	Family

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)

Substrate kinetics (BRENDA)

21 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
P1,P4-BIS(5’-GUANOSYL) TETRAPHOSPHATE	0.001–1.03	4
5’,5’’-DIADENOSINE TETRAPHOSPHATE	0.0006–0.003	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
2-OXO-DATP	0.3846	1
5’,5’-DIADENOSINE HEXAPHOSPHATE	0.015	1
8-OXO-DGTP	0.0986	1
AP5A	0.098	1
AP6A	0.04	1
DATP	0.1143	1

Catalyzed reactions (Rhea), 3 shown:

• P(1),P(4)-bis(5’-guanosyl) tetraphosphate + H2O = GMP + GTP + 2 H(+) (RHEA:22484)
• a 5’-end FAD-phospho-ribonucleoside in mRNA + H2O = a 5’-end phospho-adenosine-phospho-ribonucleoside in mRNA + FMN + 2 H(+) (RHEA:67588)
• a 5’-end CoA-ribonucleoside in mRNA + H2O = a 5’-end phospho-adenosine-phospho-ribonucleoside in mRNA + (R)-4’-phosphopantetheine + 2 H(+) (RHEA:67592)

UniProt features (18 total): strand 7, helix 4, initiator methionine 1, chain 1, domain 1, short sequence motif 1, modified residue 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4ICK	X-RAY DIFFRACTION	2.1
4IJX	X-RAY DIFFRACTION	2.1
3U53	X-RAY DIFFRACTION	2.71
1XSA	SOLUTION NMR
1XSB	SOLUTION NMR
1XSC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50583-F1	95.12	0.89

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3299685	Detoxification of Reactive Oxygen Species
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 168 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_ATP_BIOSYNTHETIC_PROCESS, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, chr9p13, GOBP_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_MONOPHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (5): nucleobase-containing compound metabolic process (GO:0006139), AMP biosynthetic process (GO:0006167), ATP biosynthetic process (GO:0006754), apoptotic process (GO:0006915), cellular response to oxidative stress (GO:0034599)

GO Molecular Function (7): bis(5’-nucleosyl)-tetraphosphatase (asymmetrical) activity (GO:0004081), GTP binding (GO:0005525), bis(5’-nucleosyl)-tetraphosphatase (symmetrical) activity (GO:0008803), nucleotide binding (GO:0000166), protein binding (GO:0005515), bis(5’-nucleosyl)-tetraphosphatase activity (GO:0008796), hydrolase activity (GO:0016787)

GO Cellular Component (1): mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular response to chemical stress	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleotide biosynthetic process	2
bis(5’-nucleosyl)-tetraphosphatase activity	2
primary metabolic process	1
purine ribonucleoside monophosphate biosynthetic process	1
AMP metabolic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to oxidative stress	1
cellular response to chemical stress	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
pyrophosphatase activity	1
catalytic activity	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDT2	FHIT	P49789	813
NUDT2	IL11RA	Q14626	777
NUDT2	NUDT12	Q9BQG2	772
NUDT2	NUDT17	P0C025	726
NUDT2	NUDT5	Q9UKK9	725
NUDT2	NUDT15	Q9NV35	709
NUDT2	NUDT3	O95989	708
NUDT2	NUDT9	Q9BW91	680
NUDT2	NUDT22	Q9BRQ3	676
NUDT2	CNTFR	P26992	668
NUDT2	NUDT14	O95848	666
NUDT2	NUDT18	Q6ZVK8	647
NUDT2	NUDT19	A8MXV4	613
NUDT2	NUDT1	P36639	599
NUDT2	NUDT16	Q96DE0	580

IntAct

15 interactions, top by confidence:

A	B	Type	Score
NUDT2	MCM6	psi-mi:“MI:0915”(physical association)	0.560
MCM6	NUDT2	psi-mi:“MI:0915”(physical association)	0.560
NUDT2	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
NUDT2	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
LRRK2		psi-mi:“MI:0914”(association)	0.350
ESR2	PSMD11	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
NUDT2	DDIT4L	psi-mi:“MI:0915”(physical association)	0.000
NUDT2	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): MCM6 (Two-hybrid), NUDT2 (Proximity Label-MS), NUDT2 (Affinity Capture-MS), NUDT2 (Two-hybrid), PLEKHF2 (Two-hybrid), NUDT2 (Affinity Capture-MS), NUDT2 (Affinity Capture-MS), DPP9 (Co-fractionation), DPH5 (Co-fractionation), NUDT2 (Two-hybrid), ORF7a (Affinity Capture-Western), ORF7a (Co-localization), NUDT2 (Affinity Capture-MS), NUDT2 (Affinity Capture-MS), NUDT2 (Proximity Label-MS)

ESM2 similar proteins: A1ADA3, A4WDK7, A7ZP69, A8A2B8, B1IXT6, B1LLK5, B1X8W4, B4TPH8, B5F9P6, B5R268, B5XNX5, B6I7J4, B7LAR6, B7LM80, B7M5T3, B7MG18, B7MXT2, B7N5L6, B7NN72, B7UFR3, C0Q073, C0SPC3, C4ZU93, F1P963, P08337, P0AFC0, P0AFC1, P0AFC2, P32090, P36639, P44932, P50583, P50584, P52006, P53368, P53369, P56380, P77788, Q0T2N2, Q0TFJ1

Diamond homologs: P0C996, P0C997, P0C998, P32092, P50583, P50584, Q29RJ1, Q65217, Q6PEC0, P56380, P9WIX6, P9WIX7, Q5M8V2, Q75UV1, Q9U2M7, A4FUG7, Q9SJC4, A0QUZ2, A1B502, A8LKJ8, B8H5H3, P57965, P96590, P9WIY0, P9WIY1, P9WIY2, P9WIY3, Q1GSV9, Q2N9Y3, Q58549, Q9A2W6, A1ADA3, A4WDK7, A6TBV3, A7ZP69, A8A2B8, A9MJC8, A9N5B7, B1IXT6, B1LLK5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	17
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1686822	NM_001161.5(NUDT2):c.34C>T (p.Arg12Ter)	Likely pathogenic
2446368	NM_001161.5(NUDT2):c.174G>T (p.Glu58Asp)	Likely pathogenic

SpliceAI

446 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34329598:GG:G	donor_gain	0.9900
9:34329599:GG:G	donor_gain	0.9900
9:34329600:G:GG	donor_gain	0.9900
9:34329601:T:G	donor_loss	0.9900
9:34329602:GAGTA:G	donor_loss	0.9900
9:34329595:TTCGG:T	donor_gain	0.9800
9:34329596:TCGG:T	donor_gain	0.9700
9:34329597:CGG:C	donor_gain	0.9700
9:34329598:GGG:G	donor_gain	0.9700
9:34343120:CTA:C	acceptor_loss	0.9700
9:34343121:TAG:T	acceptor_loss	0.9700
9:34343123:G:A	acceptor_loss	0.9700
9:34343123:GGCC:G	acceptor_gain	0.9700
9:34343118:A:AG	acceptor_gain	0.9600
9:34343122:A:AG	acceptor_gain	0.9600
9:34343123:G:GG	acceptor_gain	0.9600
9:34339020:TAAG:T	acceptor_gain	0.9500
9:34343119:A:G	acceptor_gain	0.9400
9:34339019:TTAAG:T	acceptor_gain	0.9300
9:34329602:G:GT	donor_gain	0.9200
9:34332780:G:T	donor_gain	0.9200
9:34338773:G:GT	donor_gain	0.9200
9:34338816:T:TA	donor_gain	0.9200
9:34338817:A:AA	donor_gain	0.9200
9:34343122:AG:A	acceptor_gain	0.9200
9:34343123:GG:G	acceptor_gain	0.9200
9:34329601:T:TG	donor_gain	0.9100
9:34329597:CGGGT:C	donor_gain	0.9000
9:34329598:GGGTG:G	donor_gain	0.9000
9:34329600:G:GC	donor_gain	0.9000

AlphaMissense

962 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34339151:T:A	W38R	0.994
9:34339151:T:C	W38R	0.994
9:34343342:T:A	W116R	0.994
9:34343342:T:C	W116R	0.994
9:34339165:A:C	K42N	0.992
9:34339165:A:T	K42N	0.992
9:34343344:G:C	W116C	0.992
9:34343344:G:T	W116C	0.992
9:34339153:G:C	W38C	0.991
9:34339153:G:T	W38C	0.991
9:34343160:C:A	A55D	0.991
9:34339074:G:C	R12P	0.990
9:34343166:G:T	R57M	0.990
9:34343170:G:C	E58D	0.990
9:34343170:G:T	E58D	0.990
9:34339161:C:A	P41H	0.989
9:34343282:G:C	A96P	0.988
9:34339115:T:C	F26L	0.987
9:34339117:T:A	F26L	0.987
9:34339117:T:G	F26L	0.987
9:34339166:G:C	G43R	0.987
9:34343183:G:C	A63P	0.987
9:34343263:A:C	K89N	0.987
9:34343263:A:T	K89N	0.987
9:34339164:A:T	K42I	0.986
9:34343167:G:C	R57S	0.986
9:34343167:G:T	R57S	0.986
9:34343166:G:C	R57T	0.985
9:34343378:T:C	F128L	0.985
9:34343380:C:A	F128L	0.985

dbSNP variants (sampled 300 via entrez): RS1000272276 (9:34333381 C>G,T), RS1000371309 (9:34339791 C>G,T), RS1000397722 (9:34339976 C>T), RS1000409862 (9:34332807 A>C), RS1000428766 (9:34340225 C>T), RS1000480790 (9:34331370 T>C), RS1000485694 (9:34339435 C>T), RS1000534118 (9:34331655 A>G,T), RS1001305324 (9:34343807 G>A), RS1001517335 (9:34331721 G>A), RS1002101133 (9:34338966 C>A,G,T), RS1002152947 (9:34329797 G>T), RS1002457180 (9:34336699 A>G), RS1002535978 (9:34329122 C>A), RS1002674241 (9:34342398 C>T)

Disease associations

OMIM: gene MIM:602852 | disease phenotypes: MIM:619844

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with or without peripheral neuropathy	Strong	Autosomal recessive

Mondo (3): intellectual developmental disorder with or without peripheral neuropathy (MONDO:0859240), intellectual disability (MONDO:0001071), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (3): Intellectual disability-peripheral neuropathy-corpus callosum abnormalities syndrome due to nudix hydrolase 2 deficiency (Orphanet:694937), Non-specific syndromic intellectual disability (Orphanet:528084), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000278	Retrognathia
HP:0000294	Low anterior hairline
HP:0000431	Wide nasal bridge
HP:0000664	Synophrys
HP:0000750	Delayed speech and language development
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001518	Small for gestational age
HP:0002033	Poor suck
HP:0002317	Unsteady gait
HP:0002359	Frequent falls
HP:0002454	Eye of the tiger anomaly of globus pallidus
HP:0003577	Congenital onset
HP:0003623	Neonatal onset
HP:0006889	Borderline intellectual disability
HP:0031936	Delayed ability to walk
HP:0033725	Thin corpus callosum

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010136_34	Fruit consumption	4.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105863 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
Estradiol	decreases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression, increases methylation	1
beta-lapachone	increases expression	1
diadenosine tetraphosphate	increases hydrolysis	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Hydrogen Peroxide	affects expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Valproic Acid	decreases methylation	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4008386	Binding	Inhibition of NUDT2 (unknown origin) by malachite green reagent based assay	Identification of Triazolothiadiazoles as Potent Inhibitors of the dCTP Pyrophosphatase 1. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1ZB	Abcam HeLa NUDT2 KO	Cancer cell line	Female
CVCL_TB38	HAP1 NUDT2 (-) 1	Cancer cell line	Male
CVCL_TB39	HAP1 NUDT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders