NT5E

Chr 6AR

5'-nucleotidase ecto

Also known as: CALJA, CD73, E5NT, NT, NT5, NTE, eN, eNT

NCBI Gene: 4907ENSG00000135318UniProt: P21589

The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

Primary Disease Associations & Inheritance

Calcification of joints and arteriesMIM #211800
AR
96
ClinVar variants
3
Pathogenic / LP
0.00
pLI score
6
Active trials
Clinical Summary— NT5E
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 85 VUS of 96 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

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.
1.18LOEUF
pLI 0.000
Z-score 0.88
OE 0.81 (0.56–1.18)
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.
0.60Z-score
OE missense 0.91 (0.82–1.00)
291 obs / 321.5 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.0.81 (0.56–1.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.82–1.00)
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.0.89
0≤1.21.6
LoF obs/exp: 19 / 23.6Missense obs/exp: 291 / 321.5Syn Z: 1.01

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS85
Likely Benign8
2
Pathogenic
1
Likely Pathogenic
85
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
1
0
1
VUS
0
82
3
0
85
Likely Benign
0
2
0
6
8
Benign
0
0
0
0
0
Total0846696

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

View in ClinVar →

Protein Context — Lollipop Plot

NT5E · 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

Calcification of joints and arteries

MIM #211800

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Multi-omics analysis of polyamine metabolism implicates NT5E/CD73 in the progression of pancreatic cancer.
Zhang E et al.·Cancer Lett
2025
Combined single-cell RNA sequencing and mendelian randomization to identify biomarkers associated with necrotic apoptosis in intervertebral disc degeneration.
Ye Y et al.·Spine J
2025
Single-cell RNA sequencing reveals distinct cellular factors for response to immunotherapy targeting CD73 and PD-1 in colorectal cancer.
Kim M et al.·J Immunother Cancer
2021
ENPP1 Immunobiology as a Therapeutic Target.
Ruiz-Fernández de Córdoba B et al.·Clin Cancer Res
2023Review
Novel microRNAs modulating ecto-5'-nucleotidase expression.
Kordaß T et al.·Front Immunol
2023
A Systems Oncology Approach Identifies NT5E as a Key Metabolic Regulator in Tumor Cells and Modulator of Platinum Sensitivity.
Nevedomskaya E et al.·J Proteome Res
2016Meta-analysis
Tumor-expressing PD-L1 regulates NT5E expression through MAPK/ERK pathway in triple-negative breast cancer.
Cheng C et al.·Oncol Res
2025
NT5E gene and CD38 protein as potential prognostic biomarkers for childhood B-acute lymphoblastic leukemia.
da Silva Nunes VB et al.·Purinergic Signal
2022
Expression and clinical significance of serum NT5E protein in patients with colorectal cancer.
Wang G et al.·Cancer Biomark
2019Cohort
Integration of osimertinib-targeted EGFR gene-associated differential gene expression in constructing a prognostic model for lung adenocarcinoma.
Li H et al.·Funct Integr Genomics
2024Functional
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
EndometriosisImmunityMicrobiota

Innate Immunity, MIcrobiota and Inovative Treatments in Endometriosis

NOT YET RECRUITING
NCT07078435Phase NAUniversity Hospital, GrenobleStarted 2025-09-09
surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelinesBlood testStool samples
Metastatic Colon AdenocarcinomaMetastatic Colorectal CarcinomaMetastatic Rectal Adenocarcinoma

Panitumumab, Regorafenib, or TAS-102, in Treating Patients With Metastatic and/or Unresectable RAS Wild-Type Colorectal Cancer

ACTIVE NOT RECRUITING
NCT03992456Phase PHASE2Academic and Community Cancer Research UnitedStarted 2020-04-24
PanitumumabQuality-of-Life AssessmentQuestionnaire Administration
Non-Small Cell Lung Cancer

Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy

ACTIVE NOT RECRUITING
NCT03334617Phase PHASE2AstraZenecaStarted 2017-12-18
DurvalumabDanvatirsenCeralasertib
Pseudoxanthoma Elasticum

Purinergic Compounds in Pseudoxanthoma Elasticum

NOT YET RECRUITING
NCT07323082Phase NACentre Hospitalier Universitaire de NiceStarted 2026-01-15
supplementary tubesSCANNER
Relapsing Multiple Sclerosis

Role of ADA SNPs in Subjects With Relapsing Multiple Sclerosis (RMS)

RECRUITING
NCT04121065Neuromed IRCCSStarted 2020-09-07
Blood withdrawal
Non Small Cell Lung Cancer

A Study to Compare Uliledlimab Combined With Toripalimab, Toripalimab Monotherapy, and Pembrolizumab Monotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1- and CD73- Selected Non-Small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT06984588Phase PHASE2, PHASE3TJ Biopharma Co., Ltd.Started 2024-03-28
UliledlimabToripalimabPembrolizumab

External Resources

Links to major genomics databases and tools