NUDT2

Chr 9AR

nudix hydrolase 2

Also known as: APAH1, IDDPN

NCBI Gene: 318ENSG00000164978UniProt: P50583

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. [provided by RefSeq, Sep 2011]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with or without peripheral neuropathyMIM #619844
AR
104
ClinVar variants
70
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— NUDT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
70 Pathogenic / Likely Pathogenic· 26 VUS of 104 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.45LOEUF
pLI 0.006
Z-score 0.82
OE 0.65 (0.32–1.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.48Z-score
OE missense 0.85 (0.70–1.04)
68 obs / 80.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.65 (0.32–1.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.70–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 4 / 6.2Missense obs/exp: 68 / 80.2Syn Z: -0.18

ClinVar Variant Classifications

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic11
VUS26
Likely Benign3
Benign2
59
Pathogenic
11
Likely Pathogenic
26
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
59
0
59
Likely Pathogenic
1
1
9
0
11
VUS
0
15
11
0
26
Likely Benign
0
2
0
1
3
Benign
0
0
2
0
2
Total118811101

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NUDT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NUDT2-related developmental disorder

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NUDIX HYDROLASE 2; NUDT2
MIM #602852 · *

Intellectual developmental disorder with or without peripheral neuropathy

MIM #619844

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel NUDT2 variant causes intellectual disability and polyneuropathy.
Diaz F et al.·Ann Clin Transl Neurol
2020Case report
Mitochondrial-related genome-wide Mendelian randomization identifies putatively causal genes in the pathogenesis of sepsis.
Sun J et al.·Surgery
2025Review
Nudix-type motif 2 in human breast carcinoma: a potent prognostic factor associated with cell proliferation.
Oka K et al.·Int J Cancer
2011
The first case of intellectual disability caused by novel compound heterozygosity for NUDT2 variants.
Bi B et al.·BMC Pediatr
2024Case report
Mapping the Proteomic Landscape of Pancreatic Cancer: Prognostic Insights and Subtype Stratification.
Aref AT et al.·Cancer Res Commun
2025
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
Anazi S et al.·Mol Psychiatry
2017
A founder nonsense variant in NUDT2 causes a recessive neurodevelopmental disorder in Saudi Arab children.
Yavuz H et al.·Clin Genet
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools