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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ADLOEUF 1.411 OMIM phenotype
Clinical SummaryNUDT15
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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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

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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