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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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IMPA2
inositol monophosphatase 2
Chromosome 18 · 18p11.21
NCBI Gene: 3613Ensembl: ENSG00000141401.13HGNC: HGNC:6051UniProt: O14732
58PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcytoplasminositol monophosphate 1-phosphatase activityprotein homodimerization activityneurodegenerative diseasealcohol drinkingbone remodeling diseasecutaneous melanoma
✦AI Summary

IMPA2 (inositol monophosphatase 2) is a phosphatase that dephosphorylates myo-inositol monophosphates and related substrates to regulate the phosphatidylinositol signaling cycle 1. The enzyme is inhibited by lithium at therapeutically relevant concentrations, implicating IMPA2 as a pharmacological target for lithium's mood-stabilizing effects 23. Genetically, IMPA2 variants have been associated with febrile seizures susceptibility on chromosome 18.2 4, and multiple studies suggest links to bipolar disorder susceptibility, with evidence for altered gene expression in affected individuals 526. Notably, IMPA2 expression correlates negatively with intracellular calcium levels in bipolar patients, suggesting involvement in calcium homeostasis dysregulation 5. Beyond neuropsychiatric disease, IMPA2 functions as an oncogene in cervical and basal-like breast cancers. IMPA2 silencing inhibits tumor proliferation and promotes paclitaxel sensitivity in cervical cancer through p53-mediated regulation 78. In breast cancer, IMPA2 upregulation promotes the myo-inositol-phosphatidylinositol cycle, elevating intracellular calcium and activating NFAT1, creating a positive feedback loop with MYC that drives aggressive tumor progression 9.

Sources cited
1
IMPA2 phosphatase substrate specificity and lithium inhibition as pharmacological target
PMID: 17068342
2
IMPA2 linkage and association with febrile seizures susceptibility on chromosome 18p11.2
PMID: 15557493
3
Altered IMPA2 expression and correlation with calcium homeostasis abnormalities in bipolar disorder
PMID: 11673796
4
IMPA2 genomic structure, chromosomal location 18p11.2, and polymorphism identification in bipolar patients
PMID: 10822345
5
Association analysis of IMPA2 polymorphisms with bipolar disorder susceptibility
PMID: 20800640
6
IMPA2 genetic variants associated with age at onset of bipolar disorder
PMID: 29499505
7
IMPA2 tumor-promoting role in cervical cancer via MAPK/ERK pathway suppression
PMID: 32409648
8
IMPA2 blocks cervical cancer apoptosis and induces paclitaxel resistance through p53-mediated AIFM2 regulation
PMID: 37140233
9
IMPA2 promotes basal-like breast cancer aggressiveness through MYC-mediated positive feedback loop and calcium signaling
PMID: 38048842
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
alcohol drinkingOpen Targets
0.17Weak
bone remodeling diseaseOpen Targets
0.11Weak
cutaneous melanomaOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
cervical cancerOpen Targets
0.09Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.07Suggestive
liver cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
ovarian cancerOpen Targets
0.04Suggestive
Genetic renal or urinary tract malformationOpen Targets
0.04Suggestive
renal hypodysplasia/aplasia 3Open Targets
0.04Suggestive
congenital hydronephrosisOpen Targets
0.04Suggestive
congenital primary megaureterOpen Targets
0.03Suggestive
bipolar disorderOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
INPP1Protein interaction96%MTM1Protein interaction94%MIOXProtein interaction93%PLCD1Protein interaction93%CDIPTProtein interaction92%INPP4AProtein interaction91%
Tissue Expression6 tissues
Lung
100%
Liver
94%
Ovary
33%
Heart
24%
Bone Marrow
23%
Brain
18%
Gene Interaction Network
Click a node to explore
IMPA2INPP1MTM1MIOXPLCD1CDIPTINPP4A
PROTEIN STRUCTURE
Preparing viewer…
PDB2FVZ · 2.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.23LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.63–1.23]
RankingsWhere IMPA2 stands among ~20K protein-coding genes
  • #7,881of 20,598
    Most Researched58
  • #12,906of 17,882
    Most Constrained (LOEUF)1.23
Genes detectedIMPA2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Linkage and association of febrile seizures to the IMPA2 gene on human chromosome 18.
PMID: 15557493
Neurology · 2004
1.00
2
Altered IMPA2 gene expression and calcium homeostasis in bipolar disorder.
PMID: 11673796
Mol Psychiatry · 2001
0.90
3
A human myo-inositol monophosphatase gene (IMPA2) localized in a putative susceptibility region for bipolar disorder on chromosome 18p11.2: genomic structure and polymorphism screening in manic-depressive patients.
PMID: 10822345
Mol Psychiatry · 2000
0.80
4
Association analysis between polymorphisms in the myo-inositol monophosphatase 2 (IMPA2) gene and bipolar disorder.
PMID: 20800640
Prog Neuropsychopharmacol Biol Psychiatry · 2010
0.70
5
IMPA2 blocks cervical cancer cell apoptosis and induces paclitaxel resistance through p53-mediated AIFM2 regulation.
PMID: 37140233
Acta Biochim Biophys Sin (Shanghai) · 2023
0.60