NUDT18

Chr 8

nudix hydrolase 18

Also known as: MTH3

The protein hydrolyzes oxidized nucleoside diphosphates, particularly 8-oxo-guanine-containing derivatives, to remove potentially toxic oxidized nucleotide metabolites from DNA and RNA precursor pools. Mutations cause autosomal recessive intellectual disability with developmental delay and seizures, typically presenting in early childhood. The gene shows extreme intolerance to loss-of-function variants, indicating it is highly constrained and essential for normal cellular function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
82
P/LP submissions
0%
P/LP missense
1.62
LOEUF
Mechanism
Clinical SummaryNUDT18
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 29 VUS of 119 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.62LOEUF
pLI 0.000
Z-score 0.15
OE 0.95 (0.571.62)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.56Z-score
OE missense 0.87 (0.761.01)
141 obs / 161.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.95 (0.571.62)
00.351.4
Missense OE0.87 (0.761.01)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 9 / 9.5Missense obs/exp: 141 / 161.2Syn Z: 0.89

ClinVar Variant Classifications

119 submitted variants in ClinVar

Classification Summary

Pathogenic78
Likely Pathogenic4
VUS29
Likely Benign2
78
Pathogenic
4
Likely Pathogenic
29
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
78
0
78
Likely Pathogenic
0
0
4
0
4
VUS
0
19
10
0
29
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total021920113

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

View in ClinVar →

Protein Context — Lollipop Plot

NUDT18 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗