NUDT2

Chr 9AR

nudix hydrolase 2

Also known as: APAH1, IDDPN

NCBI Gene: 318 ENSG00000164978 UniProt: P50583 OMIM: 602852

The NUDT2 protein is a nucleotide pyrophosphatase that hydrolyzes diadenosine tetraphosphate (Ap4A) to maintain intracellular dinucleotide levels and exhibits decapping activity towards certain RNA molecules. Biallelic mutations cause autosomal recessive intellectual developmental disorder with or without peripheral neuropathy. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.451 OMIM phenotype

Clinical Summary— NUDT2

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 17 VUS of 28 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.48Z-score

OE missense 0.85 (0.70–1.04)

68 obs / 80.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.32–1.45)

0≤0.351.4

Missense OE?0.85 (0.70–1.04)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 4 / 6.2Missense obs/exp: 68 / 80.2Syn Z: -0.18

ClinVar Variant Classifications

28 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic3

VUS17

Likely Benign3

Benign2

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	2	1	0	0	3
VUS	1	16	0	0	17
Likely Benign	0	2	0	1	3
Benign	0	0	2	0	2
Total	3	19	2	1	25

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

View in ClinVar →

68 pathogenic / likely-pathogenic (of 78) ClinVar copy-number / structural variants overlap NUDT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →