NUDT15

Chr 13AD

nudix hydrolase 15

Also known as: MTH2, NUDT15D

The enzyme catalyzes hydrolysis of nucleoside triphosphates including thiopurine drug derivatives like 6-thio-dGTP and 6-thio-GTP, serving as a negative regulator of thiopurine activation and toxicity. Mutations cause poor metabolism of thiopurines with autosomal dominant inheritance, leading to thiopurine-induced early leukopenia in patients receiving these medications. This gene shows low constraint against loss-of-function variants, indicating tolerance to such mutations in the general population.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

{Thiopurines, poor metabolism of, 2}MIM #616903
AD
2
Active trials
72
Pubs (1 yr)
67
P/LP submissions
0%
P/LP missense
1.41
LOEUF
Mechanism
Clinical SummaryNUDT15
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
67 unique Pathogenic / Likely Pathogenic· 19 VUS of 92 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.41LOEUF
pLI 0.002
Z-score 0.81
OE 0.68 (0.351.41)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.07Z-score
OE missense 0.98 (0.821.18)
83 obs / 84.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.351.41)
00.351.4
Missense OE0.98 (0.821.18)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 5 / 7.4Missense obs/exp: 83 / 84.8Syn Z: -0.50

ClinVar Variant Classifications

92 submitted variants in ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic2
VUS19
Likely Benign4
Benign1
65
Pathogenic
2
Likely Pathogenic
19
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
65
0
65
Likely Pathogenic
0
0
2
0
2
VUS
1
12
6
0
19
Likely Benign
0
0
1
3
4
Benign
0
0
1
0
1
Total11275391

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

View in ClinVar →

Protein Context — Lollipop Plot

NUDT15 · protein map & ClinVar variants

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

Clinical Literature
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