NT5C2
5'-Nucleotidase, Cytosolic II; Key Regulator of Purine Metabolism and Drug Resistance in Leukemia
Gene Information Card
| Symbol | NT5C2 |
|---|---|
| Full Name | 5'-Nucleotidase, Cytosolic II |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 22978 ncbi.nlm.nih.gov/gene/22978 |
| Ensembl ID | ENSG00000119912 |
| UniProt ID | P49902 |
| OMIM ID | 600417 |
| HGNC ID | 8022 |
| Aliases | NT5CP, cN-II, GMP, IMP 5'-nucleotidase |
Description
NT5C2 encodes cytosolic 5'-nucleotidase II (cN-II), a key enzyme in purine nucleotide metabolism that dephosphorylates inosine monophosphate (IMP) and guanosine monophosphate (GMP), regulating intracellular nucleotide pools. Gain-of-function mutations in NT5C2 are a major mechanism of acquired resistance to thiopurine chemotherapy (e.g., 6-mercaptopurine) in relapsed acute lymphoblastic leukemia (ALL).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute lymphoblastic leukemia (relapsed) | Gain-of-function mutations (e.g., R367Q, D407A) increase nucleotidase activity, reducing active thiopurine metabolites (e.g., 6-TGN) and conferring drug resistance. | ClinVar, COSMIC, PMID: 23871208, PMID: 23996088 |
| Purine nucleoside phosphorylase deficiency (secondary) | Altered purine metabolism due to NT5C2 dysregulation may contribute to immune dysfunction. | OMIM #600417 |
| Cancer (general) | Somatic NT5C2 mutations found in various cancers, linked to chemotherapy resistance. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebellum) | 9.8 | Medium |
| Heart | 8.2 | Medium |
| Liver | 6.1 | Low |
| Kidney | 5.4 | Low |
| Lung | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HEK 293 (embryonic kidney) | 10.1 | Moderate expression |
| HeLa (cervical) | 8.5 | Moderate expression |
| MCF7 (breast) | 6.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R367Q | Missense | ~10% in relapsed ALL | Gain-of-function; increases catalytic efficiency for IMP/GMP |
| D407A | Missense | ~5% in relapsed ALL | Gain-of-function; alters substrate binding |
| K359Q | Missense | Rare | Gain-of-function; enhances nucleotidase activity |
| S172F | Missense | Rare | Gain-of-function; associated with thiopurine resistance |
Mutation functional classification
Loss of Function (LOF)
Not reported as a common mechanism; loss-of-function variants are rare and not linked to disease.
Gain of Function (GOF)
Recurrent missense mutations (e.g., R367Q, D407A) increase cN-II activity, reducing thiopurine drug efficacy in ALL.
Dominant Negative (DN)
Not described for NT5C2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Purine metabolism (KEGG: hsa00230)
• Thiopurine metabolism (Reactome: R-HSA-158324)
Protein Summary
The NT5C2 protein (cN-II) is a 561-amino-acid cytosolic enzyme that preferentially dephosphorylates IMP and GMP, regulating purine nucleotide pools. It exists as a homotetramer and is allosterically activated by ATP and inhibited by inorganic phosphate. Gain-of-function mutations in the C-terminal domain enhance catalytic activity, leading to resistance to thiopurine prodrugs in leukemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NT5C2 Knockout HEK293 Cell Line | EDJ-KQ7761 | Human | 22978 | Details Get a Quote |
| NT5C2 Knockout A-549 Cell Line | EDJ-KQ33213 | Human | 22978 | Details Get a Quote |
| NT5C2 Knockout HCT 116 Cell Line | EDJ-KQ33214 | Human | 22978 | Details Get a Quote |
| NT5C2 Knockout HeLa Cell Line | EDJ-KQ33215 | Human | 22978 | Details Get a Quote |
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