ITPKC: Inositol-Trisphosphate 3-Kinase C
A key regulator of calcium signaling and immune response, implicated in Kawasaki disease and inflammatory disorders.
Gene Information Card
| Symbol | ITPKC |
|---|---|
| Full Name | Inositol-Trisphosphate 3-Kinase C |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 80271 ncbi.nlm.nih.gov/gene/80271 |
| Ensembl ID | ENSG00000104825 |
| UniProt ID | Q96DU7 |
| OMIM ID | 609390 |
| HGNC ID | 6178 |
| Aliases | IP3KC, IP3-3KC, IP3Kc, MGC138215 |
Description
ITPKC encodes inositol-trisphosphate 3-kinase C, an enzyme that phosphorylates inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4). This activity regulates intracellular calcium signaling by modulating IP3 levels. ITPKC is highly expressed in immune cells and plays a critical role in T-cell activation and inflammatory responses. Genetic variants in ITPKC are associated with susceptibility to Kawasaki disease and coronary artery lesions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Kawasaki disease | ITPKC SNP rs28493229 reduces enzyme activity, leading to increased IP3 and enhanced calcium signaling in immune cells, promoting hyperinflammation and coronary artery damage. | OMIM 609390; Onouchi et al. (2008) Nat Genet |
| Coronary artery aneurysm (in Kawasaki disease) | Same mechanism as above; reduced ITPKC function exacerbates vascular inflammation. | ClinVar; Onouchi et al. (2008) |
| Systemic juvenile idiopathic arthritis | ITPKC variants may contribute to dysregulated calcium signaling and IL-1β production. | NCBI Gene; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Whole blood | 8.9 | Medium |
| Bone marrow | 7.3 | Low |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.3 | High expression; relevant for T-cell signaling studies |
| K562 (erythroleukemia) | 6.8 | Moderate expression |
| HEK293 (embryonic kidney) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs28493229 (c.720C>G) | SNP (intronic) | ~20% in East Asian populations | Reduces ITPKC expression; associated with Kawasaki disease susceptibility |
| rs2290692 (c.−86C>T) | SNP (5' UTR) | ~15% in East Asian populations | May alter transcription factor binding; linked to Kawasaki disease |
| c.1003C>T (p.Arg335Trp) | Missense | Rare | Predicted damaging; potential loss of kinase activity |
Mutation functional classification
Loss of Function (LOF)
rs28493229 reduces ITPKC expression, leading to decreased IP3 phosphorylation and prolonged calcium signaling.
Gain of Function (GOF)
No known gain-of-function mutations reported.
Dominant Negative (DN)
Not described for ITPKC.
View complete mutation data：
Gene Ontology (GO)
| • inositol trisphosphate 3-kinase activity (GO:0000822) | • protein binding (GO:0005515) |
| • cytoplasm (GO:0005737) | • inositol phosphate biosynthetic process (GO:0032958) |
| • elevation of cytosolic calcium ion concentration (GO:0051482) |
Pathways
• Inositol phosphate metabolism (Reactome: R-HSA-1483249)
• IP3 and IP4 signaling (Reactome: R-HSA-1855204)
• Calcium signaling pathway (KEGG: hsa04020)
Protein Summary
ITPKC is a 416-amino acid protein (UniProt Q96DU7) belonging to the inositol trisphosphate 3-kinase family. It catalyzes the conversion of IP3 to IP4, thereby terminating IP3-mediated calcium release from the endoplasmic reticulum. The protein contains a conserved catalytic domain and is predominantly expressed in hematopoietic tissues. ITPKC deficiency leads to exaggerated calcium flux and NFAT activation, contributing to immune hyperresponsiveness.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITPKC Knockout HEK293 Cell Line | EDJ-KQ51742 | Human | 80271 | Details Get a Quote |
| ITPKC Knockout HeLa Cell Line | EDJ-KQ57320 | Human | 80271 | Details Get a Quote |
| ITPKC Knockout A-549 Cell Line | EDJ-KQ65826 | Human | 80271 | Details Get a Quote |
| ITPKC Knockout HCT 116 Cell Line | EDJ-KQ74249 | Human | 80271 | Details Get a Quote |
