NUDT15

nudix hydrolase 15, the group of Nudix hydrolase family

Basic information

Region (hg38): 13:48037726-48047221

Links

ENSG00000136159 ∙ NCBI:55270 ∙ OMIM:615792 ∙ HGNC:23063 ∙ Uniprot:Q9NV35 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thiopurines, poor metabolism of, 2	AD	Pharmacogenomic	Individuals have been reported as having severe hematopoietic toxicity when treated with standard doses of thiopurines, and awareness may allow adjustments to the medication regimen	General	25108385; 26878724

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NUDT15 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUDT15 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			4	1		5
nonsense						0
start loss						0
frameshift						0
inframe indel				2		2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	4	6	1

Variants in NUDT15

This is a list of pathogenic ClinVar variants found in the NUDT15 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-48037755-C-T			Likely benign (May 01, 2022)
13-48037771-G-T			Uncertain significance (Aug 01, 2024)
13-48037782-A-C			Likely benign (Oct 01, 2024)
13-48037782-AGGAGTC-A			Likely benign (Sep 01, 2023)
13-48037782-A-AGGAGTC		Thiopurines, poor metabolism of, 2 • NUDT15-related disorder	Likely benign; drug response (Jul 22, 2021)
13-48037798-G-A		Thiopurines, poor metabolism of, 2 • NUDT15-related disorder	Likely benign; drug response (Mar 11, 2019)
13-48037820-A-C		not specified	Uncertain significance (May 03, 2023)
13-48037823-C-A		not specified	Uncertain significance (Feb 08, 2023)
13-48037831-G-A		not specified	Uncertain significance (Oct 08, 2024)
13-48037858-G-C		not specified	Uncertain significance (Jan 27, 2022)
13-48037869-C-A		NUDT15-related disorder	Likely benign (Oct 01, 2024)
13-48040948-G-A		not specified	Uncertain significance (Feb 07, 2023)
13-48045719-C-T		Thiopurines, poor metabolism of, 2 • azathioprine response - Toxicity • mercaptopurine response - Dosage • NUDT15-related disorder	drug response (Mar 24, 2021)
13-48045720-G-A		Thiopurines, poor metabolism of, 2	drug response (Oct 25, 2016)
13-48045806-G-A		NUDT15-related disorder	Benign (Nov 11, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NUDT15	protein_coding	protein_coding	ENST00000258662	3	9656

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00167	0.718	125588	0	160	125748	0.000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0677	83	84.8	0.979	0.00000370	1049
Missense in Polyphen		24	29.278	0.81973		376
Synonymous	-0.499	35	31.4	1.11	0.00000137	310
Loss of Function	0.815	5	7.39	0.677	3.14e-7	89

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000313	0.000299
Ashkenazi Jewish	0.00	0.00
East Asian	0.000169	0.000163
Finnish	0.00583	0.00514
European (Non-Finnish)	0.000279	0.000237
Middle Eastern	0.000169	0.000163
South Asian	0.000303	0.000294
Other	0.000533	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May catalyze the hydrolysis of nucleoside triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP and the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP (PubMed:26238318). Could also catalyze the hydrolysis of some nucleoside diphosphate derivatives (PubMed:22556419, PubMed:26238318). Hydrolyzes oxidized nucleosides triphosphates like 8-oxo-dGTP in vitro, but the specificity and efficiency towards these substrates are low. Therefore, the potential in vivo sanitizing role of this enzyme, that would consist in removing oxidatively damaged forms of nucleosides to prevent their incorporation into DNA, is unclear (PubMed:26238318, PubMed:22556419). Through the hydrolysis of thioguanosine triphosphates may participate in the catabolism of thiopurine drugs (PubMed:26238318, PubMed:25108385). May also have a role in DNA synthesis and cell cycle progression by stabilizing PCNA (PubMed:19419956). {ECO:0000269|PubMed:19419956, ECO:0000269|PubMed:22556419, ECO:0000269|PubMed:25108385, ECO:0000269|PubMed:26238318}.
• Pathway: Nucleobase catabolism;Metabolism of nucleotides;Metabolism;Phosphate bond hydrolysis by NUDT proteins;Purine catabolism (Consensus)

Intolerance Scores

• loftool: 0.755
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.523
• hipred: N
• hipred_score: 0.256
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.508

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nudt15

Gene ontology

• Biological process: mitotic cell cycle;purine nucleotide catabolic process;dGTP catabolic process;nucleobase-containing small molecule catabolic process;DNA protection;exogenous drug catabolic process;regulation of proteasomal protein catabolic process;nucleoside phosphate catabolic process
• Cellular component: cytosol
• Molecular function: protein binding;8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity;nucleoside-diphosphatase activity;NADH pyrophosphatase activity;8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity;metal ion binding;nucleoside-triphosphate diphosphatase activity