GeneBe

NUDT1

protein-coding

nudix hydrolase 1, the group of Nudix hydrolase family

Gene summary

Misincorporation of oxidized nucleoside triphosphates into DNA/RNA during replication and transcription can cause mutations that may result in carcinogenesis or neurodegeneration. The protein encoded by this gene is an enzyme that hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates, thereby preventing misincorporation. The encoded protein is localized mainly in the cytoplasm, with some in the mitochondria, suggesting that it is involved in the sanitization of nucleotide pools both for nuclear and mitochondrial genomes. Several alternatively spliced transcript variants, some of which encode distinct isoforms, have been identified. Additional variants have been observed, but their full-length natures have not been determined. A rare single-nucleotide polymorphism that results in the production of an additional, longer isoform (p26) has been described. [provided by RefSeq, Dec 2018]

Previous symbols:
  • MTH1

MANE transcript

NM_002452.4

Inheritance

—

ClinVar variants

U:31B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.59

Max pathogenic AF

—

Genomic locus

chr7:2,242,226-2,251,146

External References & Databases

Ensembl (ENSG00000106268)NCBI Gene (4521)OMIM (600312)HGNC:8048GenCCUniProt (P36639)AlphaFoldClinVar (NUDT1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~8.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NUDT1 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 30
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002452.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
 2
missense
30
clinvar
2
clinvar
 32
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00313034
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002452.4RefSeqNP_002443.33MANE Select
ENST00000356714.6EnsemblENSP00000349148.13MANE Select
NM_001367553.1RefSeqNP_001354482.13Standard
NM_001367554.1RefSeqNP_001354483.13Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Nucleobase catabolism
  • Metabolism of nucleotides
  • Metabolism
  • oxidized GTP and dGTP detoxification
  • Phosphate bond hydrolysis by NUDT proteins

Biological Process

  • purine nucleotide catabolic process
  • dGTP catabolic process
  • DNA repair
  • response to oxidative stress
  • aging

Molecular Function

  • GTPase activity
  • protein binding
  • 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity
  • snoRNA binding
  • 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity

Cellular Component

  • acrosomal vesicle
  • extracellular space
  • nucleus
  • cytoplasm
  • mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000397049
Coding exons
4
Length
8925
Individuals with no LoFs
125647
Homozygous LoFs
1
Heterozygous LoFs
100
Defined
125748
p
0.000402
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.6071271091.160.000006841189
Missense (PolyPhen)3533.3641.049377
Synonymous-0.4474844.21.090.00000314334
Loss of Function-1.63148.791.595.56e-781

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000960.00095rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000110.00011rare
Finnish0.0000930.000092rare
European (Non-Finnish)0.000220.00022rare
South Asian0.00110.0011notable
Other0.000210.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Antimutagenic (PubMed:8226881, PubMed:7713500, PubMed:10608900). Plays a redundant role in sanitizing oxidized nucleotide pools, such as 8-oxo-dGTP pools (PubMed:28679043). Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress (PubMed:12857738, PubMed:24695224, PubMed:24695225). Hydrolyzes 8- oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions (PubMed:8226881, PubMed:10373420, PubMed:10608900, PubMed:11756418, PubMed:12857738, PubMed:16607562, PubMed:24695224, PubMed:24695225, PubMed:26999531, PubMed:28035004). Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP (PubMed:10373420, PubMed:11139615). Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA (By similarity). {ECO:0000250|UniProtKB:P53368, ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:10608900, ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:11756418, ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:22556419, ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225, ECO:0000269|PubMed:26999531, ECO:0000269|PubMed:28035004, ECO:0000269|PubMed:28679043, ECO:0000269|PubMed:7713500, ECO:0000269|PubMed:8226881}.;

Recessive Scores

pRec
0.180

Intolerance Scores

LoFtool
0.997
RVIS EVS
-0.03
RVIS percentile EVS
51.92

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.987

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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