NT5C

Chr 17

5', 3'-nucleotidase, cytosolic

Also known as: DNT, DNT1, HEL74, P5N2, PN-I, PN-II, UMPH2, cdN

NCBI Gene: 30833UniProt: Q8TCD5

This gene encodes a nucleotidase that catalyzes the dephosphorylation of the 5' deoxyribonucleotides (dNTP) and 2'(3')-dNTP and ribonucleotides, but not 5' ribonucleotides. Of the different forms of nucleotidases characterized, this enzyme is unique in its preference for 5'-dNTP. It may be one of the enzymes involved in regulating the size of dNTP pools in cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2011]

0
Active trials
58
ClinVar variants
12
Pathogenic / LP
-0.3
Missense Z
1.25
LOEUF
9
Pubs (2 yr)
Clinical Summary— NT5C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 45 VUS of 58 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/NT5C?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.25LOEUF
pLI 0.003
Z-score 1.08
OE 0.60 (0.31–1.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.25Z-score
OE missense 1.07 (0.92–1.26)
108 obs / 100.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.31–1.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.92–1.26)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 5 / 8.4Missense obs/exp: 108 / 100.9Syn Z: 0.60

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS45
Likely Benign1
11
Pathogenic
1
Likely Pathogenic
45
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
0
37
8
0
45
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03820058

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

View in ClinVar →

Protein Context — Lollipop Plot

NT5C · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Insight into telomere regulation: road to discovery and intervention in plasma drug-protein targets
Ding K et al.·BMC Genomics
2024
Identification and Validation of Nicotinamide Metabolism-Related Gene Signatures as a Novel Prognostic Model for Hepatocellular Carcinoma.
Yang S et al.·Onco Targets Ther
2024Functional
Causal effects and mediation pathways of circulating plasma proteins on osteoporosis: a two-sample and two-step Mendelian randomization study.
Wang H et al.·Clin Proteomics
2025
Druggable Genome-Wide Mendelian Randomization Identifies Distinct Therapeutic Targets for Low Back Pain, Intervertebral Disk Degeneration, and Sciatica.
Sun A et al.·J Pain Res
2025
Fludarabine metabolism by cytosolic 5'-nucleotidase III and its tissue-specific localization mapping using mass spectrometry imaging.
Khan M et al.·Drug Metab Dispos
2025
Genome-Wide Association Analysis Revealed Candidate Genes Related to Early Growth Traits in Inner Mongolia Cashmere Goats.
Rong Y et al.·Vet Sci
2025
Potential drug targets for myocardial infarction identified through Mendelian randomization analysis and Genetic colocalization
Wu J et al.·Medicine (Baltimore)
2023
Prioritising genetic findings for drug target identification and validation.
Hukerikar N et al.·Atherosclerosis
2024
Combined deletion of cytosolic 5'-nucleotidases IA and II lowers glycemia by improving skeletal muscle insulin action and lowering hepatic glucose production
Jacobs R et al.·J Biol Chem
2025
A hot and cold tumor-related prognostic signature for stage II colorectal cancer
Zhou M et al.·Oncol Lett
2024
Top 10 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients