NT5C3A: 5'-Nucleotidase, Cytosolic IIIA
A key enzyme in pyrimidine nucleotide metabolism, associated with hemolytic anemia and potential roles in cancer and immune function.
Gene Information Card
| Symbol | NT5C3A |
|---|---|
| Full Name | 5'-Nucleotidase, Cytosolic IIIA |
| Gene Type | Protein-coding |
| Chromosomal Location | 7p14.3 |
| NCBI Gene ID | 51251 ncbi.nlm.nih.gov/gene/51251 |
| Ensembl ID | ENSG00000106633 |
| UniProt ID | Q9H0P0 |
| OMIM ID | 606224 |
| HGNC ID | 17899 |
| Aliases | UMPH-1, P5'N-1, NT5C3, dNT-1, P5'N1 |
Description
The NT5C3A gene encodes a cytosolic 5'-nucleotidase (EC 3.1.3.5) that preferentially dephosphorylates pyrimidine nucleoside monophosphates (e.g., UMP, CMP) to their corresponding nucleosides. This enzyme plays a critical role in pyrimidine nucleotide homeostasis and is essential for normal erythrocyte maturation. Mutations in NT5C3A cause a form of hereditary hemolytic anemia due to pyrimidine-5'-nucleotidase deficiency. The gene is also implicated in cancer cell metabolism and immune response modulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Hemolytic Anemia (Pyrimidine-5'-Nucleotidase Deficiency) | Loss-of-function mutations reduce enzyme activity, leading to accumulation of pyrimidine nucleotides in erythrocytes, causing hemolysis and anemia. | OMIM #266120; multiple case reports and functional studies. |
| Chronic Lymphocytic Leukemia (CLL) | Altered NT5C3A expression may affect nucleotide pools and sensitivity to nucleoside analog drugs. | Expression profiling studies (e.g., NCBI GEO). |
| Colorectal Cancer | Dysregulation of pyrimidine metabolism via NT5C3A may influence tumor growth. | Gene expression data from TCGA. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Liver | 6.1 | Low |
| Whole Blood | 4.2 | Low |
| Lymph Node | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression |
| HepG2 (liver) | 7.8 | Moderate expression |
| A549 (lung) | 5.1 | Low expression |
| MCF7 (breast) | 3.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.136C>T (p.Arg46Trp) | Missense | Rare | Reduced enzyme activity; associated with hemolytic anemia. |
| c.404G>A (p.Arg135Gln) | Missense | Rare | Impaired catalytic function; reported in hemolytic anemia. |
| c.719T>C (p.Leu240Pro) | Missense | Rare | Structural destabilization; loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most reported missense mutations (e.g., p.Arg46Trp, p.Arg135Gln) result in reduced or absent enzyme activity, leading to pyrimidine-5'-nucleotidase deficiency and hemolytic anemia.
Gain of Function (GOF)
No gain-of-function mutations have been documented for NT5C3A.
Dominant Negative (DN)
No dominant-negative effects have been reported; the condition is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • 5'-nucleotidase activity (GO:0008253) | • nucleotide catabolic process (GO:0009166) |
| • cytoplasm (GO:0005737) | • identical protein binding (GO:0042802) |
| • hydrolase activity (GO:0016787) |
Pathways
• Pyrimidine metabolism (Reactome: R-HSA-8956321)
• Nucleotide salvage pathway (KEGG: hsa00240)
Protein Summary
The NT5C3A protein is a 286-amino acid cytosolic enzyme that catalyzes the dephosphorylation of pyrimidine nucleoside monophosphates. It is a homodimer with each subunit containing a conserved nucleotidase domain. The enzyme is highly expressed in erythroid cells and is critical for maintaining balanced nucleotide pools. Deficiency leads to accumulation of pyrimidine nucleotides, causing hemolytic anemia. The protein also interacts with other nucleotide-metabolizing enzymes and may influence cellular responses to chemotherapeutic agents.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NT5C3A Knockout HEK293 Cell Line | EDJ-KQ51298 | Human | 51251 | Details Get a Quote |
| NT5C3A Knockout HeLa Cell Line | EDJ-KQ56260 | Human | 51251 | Details Get a Quote |
| NT5C3A Knockout A-549 Cell Line | EDJ-KQ64749 | Human | 51251 | Details Get a Quote |
| NT5C3A Knockout HCT 116 Cell Line | EDJ-KQ73195 | Human | 51251 | Details Get a Quote |
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