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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IPPK
inositol-pentakisphosphate 2-kinase
Chromosome 9 · 9q22.31
NCBI Gene: 64768Ensembl: ENSG00000127080.10HGNC: HGNC:14645UniProt: Q9H8X2
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindinginositol-1,3,4,5,6-pentakisphosphate 2-kinase activitymolecular adaptor activitypositive regulation of transcription of nucleolar large rRNA by RNA polymerase Icervical carcinomaovarian dysfunctioninflammatory bowel diseasepoisoning
✦AI Summary

IPPK (inositol-pentakisphosphate 2-kinase) is a key enzyme in inositol phosphate metabolism that phosphorylates inositol-1,3,4,5,6-pentakisphosphate (IP5) to generate inositol hexakisphosphate (IP6) 1. This enzyme is essential for multiple cellular processes, with IP6 serving critical regulatory functions. IPPK and its product IP6 are required for mRNA export from the nucleus, as IPPK depletion results in altered cytoplasmic mRNA expression and specific cell cycle defects including G1/S arrest 2. The IP6 pathway is also necessary for RNA editing in C. elegans, where IP6 deficiency enhances antiviral RNAi responses 3. In programmed cell death, IP6 directly binds and activates the necroptosis executor MLKL by destabilizing its auto-inhibitory region, with IPPK deletion abolishing IP6 production and inhibiting necroptosis 1. IPPK plays a crucial role in viral replication, particularly for HIV-1, where IP6 promotes viral particle assembly and maturation in T cells, with IPPK knockout significantly reducing infectious particle production 45. Additionally, IPPK mutations may contribute to endometrial cancer progression through effects on immune regulation 6, and dysregulation of IPPK-related pathways has been implicated in alopecia areata 7.

Sources cited
1
IPPK phosphorylates IP5 to form IP6, which directly binds MLKL to activate necroptosis
PMID: 31031142
2
IPPK depletion alters cytoplasmic mRNA expression and causes G1/S cell cycle arrest
PMID: 29746542
3
IP6 pathway is required for RNA editing and moderates antiviral RNAi responses in C. elegans
PMID: 39602251
4
IPPK knockout in T cells reduces HIV-1 particle production and infectivity
PMID: 33476323
5
IPPK is required for HIV-1 assembly and infectious particle production
PMID: 32776974
6
IPPK mutations may contribute to endometrial cancer through NLRC5 downregulation
PMID: 35880269
7
IPPK dysregulation is implicated in alopecia areata through inositol phosphorylation pathways
PMID: 38925555
Disease Associationsⓘ20
cervical carcinomaOpen Targets
0.24Weak
ovarian dysfunctionOpen Targets
0.24Weak
inflammatory bowel diseaseOpen Targets
0.17Weak
poisoningOpen Targets
0.17Weak
sinoatrial node disorderOpen Targets
0.17Weak
Crohn's diseaseOpen Targets
0.16Weak
ileostomyOpen Targets
0.08Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
infectionOpen Targets
0.05Suggestive
trauma complicationOpen Targets
0.04Suggestive
cataractOpen Targets
0.04Suggestive
HIV-1 infectionOpen Targets
0.03Suggestive
diabetic nephropathyOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
Aarskog-Scott syndrome, X-linkedOpen Targets
0.01Suggestive
type 1 diabetes mellitusOpen Targets
0.01Suggestive
cryptococcosisOpen Targets
0.00Suggestive
hearing lossOpen Targets
0.00Suggestive
venous thromboembolismOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ITPK1Protein interaction97%PPIP5K1Protein interaction86%PPIP5K2Protein interaction84%IPMKProtein interaction76%IP6K1Protein interaction71%IP6K3Protein interaction71%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
97%
Heart
82%
Lung
48%
Ovary
39%
Liver
38%
Gene Interaction Network
Click a node to explore
IPPKITPK1PPIP5K1PPIP5K2IPMKIP6K1IP6K3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9H8X2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.51Moderately Constrained
pLIⓘ
0.98Intolerant
Observed/Expected LoF0.33 [0.22–0.51]
RankingsWhere IPPK stands among ~20K protein-coding genes
  • #13,933of 20,598
    Most Researched21
  • #3,073of 17,882
    Most Constrained (LOEUF)0.51 · top quartile
Genes detectedIPPK
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NLRC5 Might Promote Endometrial Cancer Progression by Inducing PD-L1 Expression.
PMID: 35880269
Technol Cancer Res Treat · 2022
1.00
2
PMID: 39602251
Proc Natl Acad Sci U S A · 2024
0.90
3
The Crises of Oedipus.
PMID: 37098258
Psychoanal Q · 2023
0.80
4
Direct Activation of Human MLKL by a Select Repertoire of Inositol Phosphate Metabolites.
PMID: 31031142
Cell Chem Biol · 2019
0.70
5
Primate lentiviruses require Inositol hexakisphosphate (IP6) or inositol pentakisphosphate (IP5) for the production of viral particles.
PMID: 32776974
PLoS Pathog · 2020
0.60