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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NUDT2
nudix hydrolase 2
Chromosome 9 Β· 9p13.3
NCBI Gene: 318Ensembl: ENSG00000164978.20HGNC: HGNC:8049UniProt: P50583
37PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Apoptosis
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingbis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activityAMP biosynthetic processATP biosynthetic processintellectual developmental disorder with or without peripheral neuropathyIntellectual disabilitypolyneuropathyHypotonia
✦AI Summary

NUDT2 (nudix hydrolase 2) is a mitochondrial nucleotide hydrolase with dual enzymatic functions critical for cellular metabolism and gene regulation. Primarily, NUDT2 catalyzes asymmetric hydrolysis of diadenosine tetraphosphate (Ap4A) to produce AMP and ATP, and exhibits mRNA decapping activity toward FAD-capped and dpCoA-capped RNAs 1. The enzyme functions as a positive regulator of mTORC1 activation by binding Rag GTPases and controlling their lysosomal translocation, thereby promoting cell proliferation 2. NUDT2 dysregulation drives multiple cancer types through anchorage-independent growth and epithelial-mesenchymal transition. In melanoma, NUDT2 knockdown suppresses tumor growth and migration in xenograft models by reducing vimentin expression 3. In breast cancer, NUDT2 expression correlates with adverse clinical outcomes and serves as an independent prognostic factor 4. Conversely, NUDT2 disruption elevates Ap4A levels, down-regulating tumor-promotion genes while up-regulating interferon-responsive and pro-apoptotic pathways 5. Biallelic NUDT2 variants cause neurodevelopmental disease characterized by intellectual disability, motor delay, and gait disturbance, with some patients exhibiting peripheral neuropathy and basal ganglia abnormalities 1. Loss of NUDT2 decapping activity alters mRNA homeostasis and transcriptome stability 1. Additionally, NUDT2 associates with sepsis and hyperuricemia risk through mitochondrial dysfunction pathways 67.

Sources cited
1
NUDT2 catalyzes mRNA decapping and Ap4A hydrolysis; biallelic variants cause neurodevelopmental disease with intellectual disability and motor developmental delay; loss of decapping activity alters mRNA homeostasis
PMID: 38141063
2
NUDT2 regulates mTORC1 activation by binding Rag GTPases and controlling lysosomal translocation; critical for breast cancer cell proliferation
PMID: 28089905
3
NUDT2 promotes anchorage-independent growth and cell migration in melanoma; knockdown suppresses tumor growth in xenograft models and reduces vimentin expression
PMID: 37445693
4
NUDT2 expression is elevated in breast carcinoma; correlates with lymph node metastasis, histological grade, and adverse clinical outcomes; serves as independent prognostic factor
PMID: 20533549
5
NUDT2 disruption elevates Ap4A and down-regulates immune response, cancer promotion, and epithelial-mesenchymal transition genes while up-regulating pro-apoptotic genes
PMID: 27144453
6
NUDT2 gene expression and protein abundance associate with sepsis risk according to Mendelian randomization analysis of mitochondrial genes
PMID: 39933430
7
NUDT2 is identified as primary mitochondrial gene associated with hyperuricemia risk; NUDT2 protein levels negatively correlate with hyperuricemia risk
PMID: 40697080
Disease Associationsβ“˜21
intellectual developmental disorder with or without peripheral neuropathyOpen Targets
0.65Moderate
Intellectual disabilityOpen Targets
0.46Moderate
polyneuropathyOpen Targets
0.37Weak
developmental disorder of mental healthOpen Targets
0.37Weak
Global developmental delayOpen Targets
0.37Weak
HypotoniaOpen Targets
0.37Weak
complex neurodevelopmental disorderOpen Targets
0.27Weak
melanomaOpen Targets
0.07Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
placenta praeviaOpen Targets
0.06Suggestive
placental retentionOpen Targets
0.05Suggestive
triple-negative breast cancerOpen Targets
0.05Suggestive
metabolic syndromeOpen Targets
0.04Suggestive
adolescent idiopathic scoliosisOpen Targets
0.03Suggestive
cancerOpen Targets
0.02Suggestive
osteoarthritis, hipOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
osteoarthritis, kneeOpen Targets
0.02Suggestive
total joint arthroplastyOpen Targets
0.02Suggestive
Intellectual developmental disorder with or without peripheral neuropathyUniProt
Pathogenic Variants3
NM_001161.5(NUDT2):c.186del (p.Ala63fs)Pathogenic
NUDT2-associated condition|not provided|Intellectual developmental disorder with or without peripheral neuropathy|Intellectual disability|Complex neurodevelopmental disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 63
NM_001161.5(NUDT2):c.34C>T (p.Arg12Ter)Likely pathogenic
Intellectual developmental disorder with or without peripheral neuropathy
β˜…β˜†β˜†β˜†2024β†’ Residue 12
NM_001161.5(NUDT2):c.174G>T (p.Glu58Asp)Likely pathogenic
Intellectual developmental disorder with or without peripheral neuropathy
β˜…β˜†β˜†β˜†2023β†’ Residue 58
View on ClinVar β†—
Related Genes
NME1Protein interaction99%NME2Protein interaction97%GUCY1A1Protein interaction97%NME1-NME2Protein interaction96%NME4Protein interaction95%ADCY4Protein interaction95%
Tissue Expression6 tissues
Ovary
100%
Brain
87%
Liver
86%
Heart
76%
Bone Marrow
62%
Lung
51%
Gene Interaction Network
Click a node to explore
NUDT2NME1NME2GUCY1A1NME1-NME2NME4ADCY4
PROTEIN STRUCTURE
Preparing viewer…
PDB4ICK Β· 2.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.28LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.79 [0.51–1.28]
RankingsWhere NUDT2 stands among ~20K protein-coding genes
  • #10,660of 20,598
    Most Researched37
  • #4,093of 5,498
    Most Pathogenic Variants3
  • #13,489of 17,882
    Most Constrained (LOEUF)1.28
Genes detectedNUDT2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Role of Nudt2 in Anchorage-Independent Growth and Cell Migration of Human Melanoma.
PMID: 37445693
Int J Mol Sci Β· 2023
1.00
2
Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease.
PMID: 38141063
Brain Β· 2024
0.90
3
Nudix-type motif 2 contributes to cancer proliferation through the regulation of Rag GTPase-mediated mammalian target of rapamycin complex 1 localization.
PMID: 28089905
Cell Signal Β· 2017
0.80
4
Altered cognitive function in obese patients: relationship to gut flora.
PMID: 39937394
Mol Cell Biochem Β· 2025
0.70
5
NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.
PMID: 27144453
PLoS One Β· 2016
0.60