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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NT5E
5'-nucleotidase ecto
Chromosome 6 Β· 6q14.3
NCBI Gene: 4907Ensembl: ENSG00000135318.13HGNC: HGNC:8021UniProt: P21589
316PubMed Papers
21Diseases
1Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
response to ATPATP metabolic processprotein bindingplasma membranehereditary arterial and articular multiple calcification syndromeAbruptio Placentaenon-small cell lung carcinomacardiac hypertrophy
✦AI Summary

NT5E encodes CD73, a cell surface 5'-nucleotidase that catalyzes the hydrolysis of nucleotide monophosphates to release inorganic phosphate and corresponding nucleosides, with AMP being the preferred substrate 12345. The enzyme shows preference for ribonucleotide monophosphates over deoxyribose forms and processes various substrates including IMP, UMP, GMP, CMP, dAMP, dCMP, dTMP, NAD and NMN 5. Mechanistically, CD73 works in synergy with ENTPD1/CD39 to produce extracellular adenosine from ATP, participating in purinergic signaling pathways 6. In cancer contexts, NT5E/CD73 promotes immunosuppression by facilitating regulatory T cell infiltration 7, sustains cancer stem cell traits through AKT-dependent SOX9 regulation 8, and creates immunosuppressive tumor microenvironments 9. High NT5E expression correlates with poor prognosis in multiple cancers including glioblastoma, pancreatic cancer, and childhood B-acute lymphoblastic leukemia 6910. Clinically, NT5E represents a promising therapeutic target, with inhibitors like ST80 showing potential to enhance anti-PD-L1 immunotherapy effectiveness 11. The protein's role in adenosine production and subsequent immune suppression makes it a critical mediator of tumor immune evasion.

Sources cited
1
CD73 catalyzes hydrolysis of nucleotide monophosphates with AMP as preferred substrate
PMID: 21933152
2
Shows preference for ribonucleotide monophosphates and processes various substrates
PMID: 34403084
3
Works with ENTPD1/CD39 to produce extracellular adenosine from ATP and correlates with poor glioblastoma prognosis
PMID: 37402102
4
Promotes immune escape through regulatory T cell infiltration
PMID: 38969159
5
Sustains cancer stem cell traits via AKT-dependent SOX9 regulation
PMID: 32024555
6
Creates immunosuppressive environments and correlates with poor pancreatic cancer prognosis
PMID: 40582491
7
High expression predicts poor progression-free survival in childhood B-ALL
PMID: 35235138
8
Represents therapeutic target with ST80 inhibitor enhancing anti-PD-L1 therapy
PMID: 38530357
Disease Associationsβ“˜21
hereditary arterial and articular multiple calcification syndromeOpen Targets
0.72Strong
Abruptio PlacentaeOpen Targets
0.37Weak
non-small cell lung carcinomaOpen Targets
0.32Weak
cardiac hypertrophyOpen Targets
0.26Weak
Pathologic fractureOpen Targets
0.26Weak
genetic disorderOpen Targets
0.20Weak
Varicose veinsOpen Targets
0.19Weak
pericarditisOpen Targets
0.18Weak
gram-negative bacterial infectionsOpen Targets
0.17Weak
lower urinary tract calculusOpen Targets
0.17Weak
adverse effectOpen Targets
0.17Weak
response to stimulusOpen Targets
0.17Weak
ectropionOpen Targets
0.17Weak
entropionOpen Targets
0.17Weak
neoplasmOpen Targets
0.13Weak
cancerOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
lung adenocarcinomaOpen Targets
0.11Weak
head and neck squamous cell carcinomaOpen Targets
0.11Weak
Calcification of joints and arteriesUniProt
Pathogenic Variants4
NM_002526.4(NT5E):c.1608dup (p.Val537fs)Likely pathogenic
Hereditary arterial and articular multiple calcification syndrome|NT5E-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 537
NM_002526.4(NT5E):c.1428C>A (p.Cys476Ter)Likely pathogenic
NT5E-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 476
NM_002526.4(NT5E):c.662C>A (p.Ser221Ter)Pathogenic
Hereditary arterial and articular multiple calcification syndrome
β˜†β˜†β˜†β˜†2011β†’ Residue 221
NM_002526.4(NT5E):c.1073G>A (p.Cys358Tyr)Pathogenic
Hereditary arterial and articular multiple calcification syndrome
β˜†β˜†β˜†β˜†2011β†’ Residue 358
View on ClinVar β†—
Drug Targets1
OLECLUMABPhase III
5'-nucleotidase inhibitor
non-small cell lung carcinoma
Related Genes
NMNAT1Protein interaction99%UPP2Protein interaction98%UPP1Protein interaction98%EPHX2Protein interaction98%NMNAT2Protein interaction98%UPRTProtein interaction97%
Tissue Expression6 tissues
Ovary
100%
Liver
81%
Heart
33%
Brain
15%
Lung
12%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
NT5ENMNAT1UPP2UPP1EPHX2NMNAT2UPRT
PROTEIN STRUCTURE
Preparing viewer…
PDB6TVE Β· 1.05 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.25LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.00 [0.80–1.25]
RankingsWhere NT5E stands among ~20K protein-coding genes
  • #1,070of 20,598
    Most Researched316 Β· top 10%
  • #3,683of 5,498
    Most Pathogenic Variants4
  • #13,223of 17,882
    Most Constrained (LOEUF)1.25
Genes detectedNT5E
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity.
PMID: 32668225
Immunity Β· 2020
1.00
2
Tumor-derived CD109 orchestrates reprogramming of tumor-associated macrophages to dampen immune response.
PMID: 40220905
J Hepatol Β· 2025
0.90
3
NT5E gene and CD38 protein as potential prognostic biomarkers for childhood B-acute lymphoblastic leukemia.
PMID: 35235138
Purinergic Signal Β· 2022
0.80
4
CD73 sustained cancer-stem-cell traits by promoting SOX9 expression and stability in hepatocellular carcinoma.
PMID: 32024555
J Hematol Oncol Β· 2020
0.70
5
Elevated glucose levels increase vascular calcification risk by disrupting extracellular pyrophosphate metabolism.
PMID: 39529124
Cardiovasc Diabetol Β· 2024
0.60