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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ITPKA
inositol-trisphosphate 3-kinase A
Chromosome 15 · 15q15.1
NCBI Gene: 3706Ensembl: ENSG00000137825.12HGNC: HGNC:6178UniProt: P23677
39PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphatidylinositol phosphate biosynthetic processcytoskeletoninositol-1,4,5-trisphosphate 3-kinase activitycellular response to calcium ionEczematoid dermatitisallergic diseaserespiratory system diseaseasthma
✦AI Summary

ITPKA (inositol-trisphosphate 3-kinase A) is a dual-function enzyme that catalyzes phosphorylation of inositol 1,4,5-trisphosphate (InsP3) into inositol 1,3,4,5-tetrakisphosphate, regulating calcium homeostasis [UniProt]. Beyond its canonical enzymatic role, ITPKA possesses actin bundling activity 1. The protein exhibits limited expression in normal tissues but shows ectopic overexpression across multiple cancer types including lung, breast, and glioma 234. In lung adenocarcinoma, ITPKA overexpression is transcriptionally activated by TFAP2A and regulated by epigenetic gene body methylation, with methylation appearing early during malignant transformation 23. ITPKA promotes tumorigenesis through distinct mechanisms: its actin bundling activity primarily drives cancer cell migration and invasion 5, while its InsP3-kinase activity enhances these effects under specific conditions 5. In glioma, ITPKA phosphorylates PYCR1 at serine 29, stabilizing the protein and promoting oncogenic function 4. Notably, ITPKA exhibits context-dependent roles—it functions as an oncogene in most cancers but acts as a tumor suppressor in ovarian cancer through P53 stabilization and senescence induction 6. Physiologically, ITPKA participates in nociception, sensorimotor gating, and energy metabolism 7. ITPKA emerges as a potential therapeutic target and early diagnostic biomarker across multiple malignancies 8.

Sources cited
1
ITPKA is upregulated in lung and breast cancers; expression is regulated by gene body methylation; serves as early diagnostic marker
PMID: 27234602
2
ITPKA has both actin bundling and InsP3-kinase activity; overexpressed in multiple tumor types; downregulation reduces tumor growth and metastasis
PMID: 28377279
3
ITPKA overexpressed in lung adenocarcinoma, transcriptionally activated by TFAP2A; promotes EMT and interacts with DBN1; associated with poor prognosis
PMID: 32015686
4
ITPKA overexpressed in glioma; phosphorylates PYCR1 at serine 29, stabilizing protein and enhancing oncogenic function
PMID: 39170313
5
ITPKA is neuronal isoform; involved in nociception, sensorimotor gating, motor learning, and energy metabolism
PMID: 32593773
6
Actin bundling activity of ITPKA primarily accounts for migration-promoting effect; InsP3-kinase activity provides slight enhancement under ATP stimulation
PMID: 36688944
7
ITPKA acts as tumor suppressor in ovarian cancer; downregulated in ovarian cancer samples; induces senescence through MDM2-P53 interaction; negatively regulated by miR-203
PMID: 33879633
8
ITPKA identified as potential therapeutic target for ulcerative colitis through proteome-wide Mendelian randomization analysis
PMID: 36857861
Disease Associationsⓘ20
Eczematoid dermatitisOpen Targets
0.38Weak
allergic diseaseOpen Targets
0.36Weak
respiratory system diseaseOpen Targets
0.36Weak
asthmaOpen Targets
0.34Weak
Abnormal thrombosisOpen Targets
0.33Weak
allergic rhinitisOpen Targets
0.24Weak
atopic eczemaOpen Targets
0.22Weak
allergic conjunctivitisOpen Targets
0.16Weak
kidney failureOpen Targets
0.10Suggestive
upper respiratory tract disorderOpen Targets
0.09Suggestive
rhinitisOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
renal cell carcinomaOpen Targets
0.08Suggestive
deep vein thrombosisOpen Targets
0.07Suggestive
ovarian cancerOpen Targets
0.07Suggestive
atrial fibrillationOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
Barrett's esophagusOpen Targets
0.06Suggestive
childhood onset asthmaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CALM1Protein interaction99%PLCG2Protein interaction96%CALM3Protein interaction94%ITPK1Protein interaction94%INPP5JProtein interaction93%CALM2Protein interaction92%
Tissue Expression6 tissues
Brain
100%
Liver
16%
Bone Marrow
11%
Heart
10%
Ovary
4%
Lung
4%
Gene Interaction Network
Click a node to explore
ITPKACALM1PLCG2CALM3ITPK1INPP5JCALM2
PROTEIN STRUCTURE
Preparing viewer…
PDB8PP8 · 1.59 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.06Tolerant
Observed/Expected LoF0.46 [0.30–0.72]
RankingsWhere ITPKA stands among ~20K protein-coding genes
  • #10,339of 20,598
    Most Researched39
  • #5,611of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedITPKA
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Therapeutic targets for inflammatory bowel disease: proteome-wide Mendelian randomization and colocalization analyses.
PMID: 36857861
EBioMedicine · 2023
1.00
2
ITPKA Gene Body Methylation Regulates Gene Expression and Serves as an Early Diagnostic Marker in Lung and Other Cancers.
PMID: 27234602
J Thorac Oncol · 2016
0.90
3
Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is frequently over-expressed and functions as an oncogene in several tumor types.
PMID: 28377279
Biochem Pharmacol · 2017
0.80
4
TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma.
PMID: 32015686
Int J Biol Sci · 2020
0.70
5
ITPKA phosphorylates PYCR1 and promotes the progression of glioma.
PMID: 39170313
Heliyon · 2024
0.60