NT5E

Chr 6AR

5'-nucleotidase ecto

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

NCBI Gene: 4907 ENSG00000135318 UniProt: P21589 OMIM: 129190

This plasma membrane protein catalyzes the hydrolysis of extracellular nucleotide monophosphates (particularly AMP) to nucleosides, releasing inorganic phosphate. Mutations cause calcification of joints and arteries, and the protein serves as a marker of lymphocyte differentiation. The gene shows tolerance to loss-of-function variation (LOEUF 1.18), suggesting the associated phenotype may not result from simple protein loss.

OMIM ResearchSummary from RefSeq, UniProt

DNmechanismARLOEUF 1.181 OMIM phenotype

Clinical Summary— NT5E

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

4 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

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

0.60Z-score

OE missense 0.91 (0.82–1.00)

291 obs / 321.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.81 (0.56–1.18)

0≤0.351.4

Missense OE0.91 (0.82–1.00)

0≤0.61.4

Synonymous OE0.89

0≤1.21.6

LoF obs/exp: 19 / 23.6Missense obs/exp: 291 / 321.5Syn Z: 1.01

0.6550th %ile

GOF

0.6053th %ile

LOF

0.3648th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

3D Protein StructureAlphaFold

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

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

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

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

RECRUITING

NCT07323082Phase NACentre Hospitalier Universitaire de NiceStarted 2026-01-20