NT5C3A

Chr 7AR

5'-nucleotidase, cytosolic IIIA

Also known as: CNSHA8, NT5C3, P5'N-1, P5N-1, PN-I, POMP, PSN1, UMPH

NCBI Gene: 51251ENSG00000122643UniProt: Q9H0P0

This gene encodes a member of the 5'-nucleotidase family of enzymes that catalyze the dephosphorylation of nucleoside 5'-monophosphates. The encoded protein is the type 1 isozyme of pyrimidine 5' nucleotidase and catalyzes the dephosphorylation of pyrimidine 5' monophosphates. Mutations in this gene are a cause of hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and pseudogenes of this gene are located on the long arm of chromosomes 3 and 4. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Anemia, congenital, nonspherocytic hemolytic, 8MIM #266120
AR
UniProtP5N deficiency
184
ClinVar variants
44
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— NT5C3A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 77 VUS of 184 total submissions

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.
0.70LOEUF
pLI 0.015
Z-score 2.45
OE 0.36 (0.19–0.70)
Tolerant

Typical tolerance to LoF variation

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 0.95 (0.84–1.08)
173 obs / 182.4 exp
Tolerant

Mild missense constraint

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.0.36 (0.19–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.84–1.08)
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.1.05
0≤1.21.6
LoF obs/exp: 6 / 16.8Missense obs/exp: 173 / 182.4Syn Z: -0.34

ClinVar Variant Classifications

184 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic7
VUS77
Likely Benign31
Benign29
Conflicting3
37
Pathogenic
7
Likely Pathogenic
77
VUS
31
Likely Benign
29
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
27
0
37
Likely Pathogenic
3
1
3
0
7
VUS
0
66
10
1
77
Likely Benign
0
1
12
18
31
Benign
0
0
26
3
29
Conflicting
—3
Total11707822184

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

View in ClinVar →

Protein Context — Lollipop Plot

NT5C3A · protein map & ClinVar variants

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

Gene2Phenotype Curations

NT5C3A-related hemolytic anemia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Anemia, congenital, nonspherocytic hemolytic, 8

MIM #266120

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Differences in clinical characteristics and lesion proteomics between inflammatory linear verrucous epidermal nevus and local verrucous epidermal nevus.
Yuan T et al.·J Proteomics
2022
Proximity extension assay-based discovery of biomarkers for disease activity in chronic inflammatory demyelinating polyneuropathy.
Wieske L et al.·J Neurol Neurosurg Psychiatry
2024
Pyrimidine-5'-Nucleotidase Deficiency: a New Homozygous NT5C3A Mutation (c.693+1G>A variant).
Patir DC et al.·Clin Lab
2025Case report
JNJ872 inhibits influenza A virus replication without altering cellular antiviral responses.
Fu Y et al.·Antiviral Res
2016
Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes.
Livingstone M et al.·PLoS One
2015
A rare mutation (p.F149del) of the NT5C3A gene is associated with pyrimidine 5'-nucleotidase deficiency.
Bogusławska DM et al.·Cell Mol Biol Lett
2022
Comprehensive Proteomics Identification of IFN-λ3-regulated Antiviral Proteins in HBV-transfected Cells.
Makjaroen J et al.·Mol Cell Proteomics
2018
Proteomics reveals reduced expression of transketolase in pyrimidine 5'-nucleotidase deficient patients.
Barasa BA et al.·Proteomics Clin Appl
2016Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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