ITPA Gene - Inosine Triphosphatase
Genetic and Functional Insights into ITPA Deficiency and Drug Toxicity
Gene Information Card
| Symbol | ITPA |
|---|---|
| Full Name | Inosine Triphosphatase |
| Gene Type | Protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 3704 ncbi.nlm.nih.gov/gene/3704 |
| Ensembl ID | ENSG00000101444 |
| UniProt ID | Q9BY32 |
| OMIM ID | 147520 |
| HGNC ID | 6183 |
| Aliases | ITPase, C20orf37, MGC126878, MGC126880 |
Description
The ITPA gene encodes inosine triphosphatase (ITPase), a cytosolic enzyme that hydrolyzes inosine triphosphate (ITP) and deoxyinosine triphosphate (dITP) to their respective monophosphates, thereby preventing the accumulation of potentially mutagenic or cytotoxic nucleotide analogs. ITPase deficiency is associated with adverse reactions to thiopurine drugs (e.g., azathioprine, 6-mercaptopurine) and ribavirin therapy. Common hypomorphic variants (e.g., p.Pro32Thr) reduce enzyme activity and increase risk of drug-induced toxicity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| ITPA Deficiency | Loss-of-function mutations in ITPA lead to accumulation of ITP, causing hemolytic anemia and neurological symptoms. | OMIM #147520; ClinVar |
| Thiopurine Drug Toxicity | Reduced ITPase activity (e.g., p.Pro32Thr) results in accumulation of thiopurine metabolites, increasing risk of myelosuppression and flu-like symptoms. | ClinVar; NCBI Gene |
| Ribavirin-Induced Anemia | ITPA variants protect against ribavirin-induced hemolytic anemia in hepatitis C patients by altering nucleotide metabolism. | ClinVar; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 9.8 | Medium |
| Heart | 7.5 | Low |
| Brain | 5.2 | Low |
| Lung | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.5 | Hepatocellular carcinoma cell line |
| HEK293 | 11.2 | Embryonic kidney cells |
| K562 | 8.9 | Chronic myelogenous leukemia |
| HeLa | 7.3 | Cervical adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.94C>A (p.Pro32Thr) | Missense | ~6% in Europeans | Reduces ITPase activity to ~25% of normal; associated with thiopurine toxicity |
| c.124+1G>A | Splice site | Rare | Complete loss of ITPase activity; causes severe ITPA deficiency |
| c.138G>A (p.Thr46=) | Synonymous | ~2% in Asians | No effect on protein sequence; may affect splicing |
Mutation functional classification
Loss of Function (LOF)
p.Pro32Thr and splice-site variants reduce or abolish ITPase activity, leading to ITP accumulation and drug toxicity.
Gain of Function (GOF)
No gain-of-function mutations reported in ITPA.
Dominant Negative (DN)
No dominant-negative effects described; ITPA deficiency is recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Purine metabolism (KEGG: hsa00230)
• Thiopurine metabolism (Reactome: R-HSA-156581)
Protein Summary
Inosine triphosphatase (ITPase) is a 194-amino-acid homodimeric enzyme that catalyzes the hydrolysis of ITP and dITP to IMP and dIMP, respectively. It plays a critical role in purine nucleotide homeostasis and protects cells from the incorporation of non-canonical nucleotides into DNA/RNA. The enzyme is ubiquitously expressed, with highest levels in liver and kidney. Reduced ITPase activity due to common genetic variants is a well-established pharmacogenetic marker for thiopurine and ribavirin therapy outcomes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITPA Knockout HEK293 Cell Line | EDJ-KQ2607 | Human | 3704 | Details Get a Quote |
| ITPA Knockout A-549 Cell Line | EDJ-KQ23317 | Human | 3704 | Details Get a Quote |
| ITPA Knockout HCT 116 Cell Line | EDJ-KQ23318 | Human | 3704 | Details Get a Quote |
| ITPA Knockout HeLa Cell Line | EDJ-KQ23319 | Human | 3704 | Details Get a Quote |
