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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IPMK
inositol polyphosphate multikinase
Chromosome 10 · 10q21.1
NCBI Gene: 253430Ensembl: ENSG00000151151.7HGNC: HGNC:20739UniProt: Q8NFU5
45PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmflavonoid bindingprotein bindinginositol trisphosphate metabolic processneurodegenerative diseaseinflammatory bowel diseasehereditary neuroendocrine tumor of small intestinepsoriasis
✦AI Summary

IPMK (inositol polyphosphate multikinase) is a multifunctional kinase with broad substrate specificity that catalyzes phosphorylation of inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate and subsequently to inositol 1,3,4,5,6-pentakisphosphate, while also phosphorylating the signaling phospholipid PIP2 12. Beyond its canonical inositol phosphate biosynthetic role, IPMK functions as a multifactorial regulator of cellular signaling with distinct catalytic and non-catalytic mechanisms 3. Structurally, IPMK contains disordered domains that modulate ATP binding and kinase activity through an N-terminal "ATP-clamp" mechanism 2. IPMK regulates transcription and histone acetylation by controlling HDAC3 activity through IPMK-dependent inositol phosphates, particularly IP4 4. In immune signaling, IPMK interacts with TRAF6 to regulate TLR4-mediated inflammation, with LPS-triggered miR-181c-mediated downregulation modulating inflammatory responses 5. IPMK is essential for embryonic development and influences human longevity through gender-specific genetic variants 6. Clinically, IPMK dysregulation is implicated in asthma pathogenesis via HIF2α-mediated promotion of pathogenic Th2 cell differentiation through PIP3 synthesis regulation 7, positioning IPMK as a potential therapeutic target in inflammation, cancer, and neurodegeneration 3.

Sources cited
1
IPMK phosphorylates Ins(1,4,5)P3 to Ins(1,3,4,5)P4 and then to Ins(1,3,4,5,6)P5 with broad substrate specificity
PMID: 12027805
2
IPMK phosphorylates PIP2 and contains disordered domains with an ATP-clamp mechanism that modulates kinase activity
PMID: 30420721
3
IPMK is a versatile enzyme generating InsP4, InsP5, and PIP3 with roles in nutrient sensing, growth factor signaling, and transcription regulation
PMID: 41008573
4
IPMK regulates HDAC3 deacetylase activity and histone H4 acetylation through IPMK-dependent inositol phosphates
PMID: 38746349
5
IPMK interacts with TRAF6 and is downregulated by miR-181c to regulate TLR4 signaling and inflammation in macrophages
PMID: 36830701
6
IPMK genetic variants are associated with female longevity and regulate aging-related processes including telomere homeostasis and oxidative stress
PMID: 30744060
7
IPMK is transcriptionally regulated by HIF2α-GATA3 circuit to promote pathogenic Th2 cell differentiation and asthmatic inflammation via PIP3 synthesis
PMID: 39609127
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
inflammatory bowel diseaseOpen Targets
0.38Weak
hereditary neuroendocrine tumor of small intestineOpen Targets
0.37Weak
psoriasisOpen Targets
0.34Weak
ulcerative colitisOpen Targets
0.29Weak
ArthropathyOpen Targets
0.29Weak
Crohn's diseaseOpen Targets
0.29Weak
thyroiditisOpen Targets
0.25Weak
Transient global amnesiaOpen Targets
0.20Weak
myopathyOpen Targets
0.19Weak
strictureOpen Targets
0.17Weak
Abnormality of the integumentOpen Targets
0.12Weak
secondary malignant neoplasmOpen Targets
0.12Weak
Alzheimer diseaseOpen Targets
0.12Weak
biliary tract diseaseOpen Targets
0.12Weak
Parkinson diseaseOpen Targets
0.10Weak
polycythemiaOpen Targets
0.09Suggestive
Insulin resistanceOpen Targets
0.07Suggestive
non-alcoholic steatohepatitisOpen Targets
0.06Suggestive
breast cancerOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PLCG2Protein interaction96%ITPK1Protein interaction95%PLCH2Protein interaction95%INPP5JProtein interaction95%INPP5KProtein interaction95%PLCE1Protein interaction93%
Tissue Expression6 tissues
Brain
100%
Liver
98%
Lung
48%
Bone Marrow
40%
Heart
35%
Ovary
21%
Gene Interaction Network
Click a node to explore
IPMKPLCG2ITPK1PLCH2INPP5JINPP5KPLCE1
PROTEIN STRUCTURE
Preparing viewer…
PDB5W2I · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.60LoF Tolerant
pLIⓘ
0.82Intermediate
Observed/Expected LoF0.33 [0.19–0.60]
RankingsWhere IPMK stands among ~20K protein-coding genes
  • #9,466of 20,598
    Most Researched45
  • #4,113of 17,882
    Most Constrained (LOEUF)0.60 · top quartile
Genes detectedIPMK
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Hypoxia-inducible factor 2α promotes pathogenic polarization of stem-like Th2 cells via modulation of phospholipid metabolism.
PMID: 39609127
Immunity · 2024
1.00
2
IPMK regulates HDAC3 activity and histone H4 acetylation in human cells.
PMID: 38746349
bioRxiv · 2024
0.90
3
Inositol Polyphosphate Multikinase (
PMID: 30744060
Genes (Basel) · 2019
0.80
4
Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity.
PMID: 30420721
Sci Rep · 2018
0.70
5
Inositol polyphosphate multikinase (IPMK) in transcriptional regulation and nuclear inositide metabolism.
PMID: 26862216
Biochem Soc Trans · 2016
0.60