HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
IMPA1
inositol monophosphatase 1
Chromosome 8 · 8q21.13
NCBI Gene: 3612Ensembl: ENSG00000133731.11HGNC: HGNC:6050UniProt: A0A140VJL8
59PubMed Papers
21Diseases
2Drugs
2Pathogenic Variants
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
inositol monophosphate phosphatase activitylithium ion bindingphosphatidylinositol biosynthetic processphosphate-containing compound metabolic processbipolar disorderbipolar I disordermajor depressive disorderintellectual disability, autosomal recessive 59
✦AI Summary

IMPA1 (inositol monophosphatase 1) is a phosphatase that catalyzes dephosphorylation of myo-inositol monophosphates to generate free myo-inositol 12, which is essential for synthesis of phosphatidylinositols and maintaining normal brain function 3. The enzyme also dephosphorylates various inositol polyphosphates and sugar-phosphates in vitro 1. IMPA1 serves as a pharmacological target for lithium, which inhibits the enzyme to reduce PIP2 resynthesis and PLC signaling, thereby decreasing neuronal excitability—a mechanism relevant to bipolar disorder treatment 4. Beyond psychiatric applications, IMPA1 has emerged as a critical metabolic regulator in cancer: it maintains stemness in castration-resistant prostate cancer via IMPDH2 activation 5, promotes triple-negative breast cancer progression through mTOR pathway and EMT activation 6, and induces M2-type macrophage polarization in hepatocellular carcinoma 7. Clinically, loss-of-function mutations in IMPA1 cause autosomal recessive intellectual disability characterized by impaired neurogenesis 8, while IMPA2 variants show association with bipolar disorder susceptibility 9. These findings establish IMPA1 as a multifunctional enzyme with roles in normal neurodevelopment, psychiatric disorders, and cancer metabolism.

Sources cited
1
IMPA1 dephosphorylates myo-inositol monophosphates and various inositol polyphosphates
PMID: 17068342
2
IMPA1 generates myo-inositol and is involved in maintaining normal brain function
PMID: 8718889
3
IMPA1 is responsible for inositol provision required for phosphatidylinositol biosynthesis and brain function
PMID: 26416544
4
Lithium inhibits IMPA1 to reduce PIP2 resynthesis, PLC signaling, and neuronal excitability in neural cells
PMID: 38056909
5
IMPA1-derived inositol maintains prostate cancer stem cells through IMPDH2 activation, promoting castration resistance
PMID: 39470689
6
IMPA1 promotes triple-negative breast cancer progression via mTOR pathway and EMT process activation
PMID: 35796646
7
IMPA1 releases myo-inositol in hepatocellular carcinoma to induce M2-type macrophage polarization
PMID: 41347800
8
IMPA1 mutations cause intellectual disability with impaired neurogenesis in neural progenitor cells
PMID: 32839513
9
IMPA2 promoter polymorphisms associate with bipolar disorder; no association found for IMPA1 variants
PMID: 14699425
Disease Associationsⓘ21
bipolar disorderOpen Targets
0.61Moderate
bipolar I disorderOpen Targets
0.57Moderate
major depressive disorderOpen Targets
0.55Moderate
intellectual disability, autosomal recessive 59Open Targets
0.52Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
amyotrophic lateral sclerosisOpen Targets
0.30Weak
depressive disorderOpen Targets
0.29Weak
treatment resistant depressionOpen Targets
0.28Weak
autism spectrum disorderOpen Targets
0.27Weak
strokeOpen Targets
0.26Weak
aggressive behaviorOpen Targets
0.26Weak
alcohol dependenceOpen Targets
0.26Weak
carotid artery diseaseOpen Targets
0.26Weak
conduct disorderOpen Targets
0.26Weak
internal carotid artery stenosisOpen Targets
0.26Weak
neutropeniaOpen Targets
0.26Weak
schizophreniaOpen Targets
0.26Weak
Cornelia de Lange syndromeOpen Targets
0.18Weak
Spinocerebellar ataxia type 3Open Targets
0.18Weak
Intellectual developmental disorder, autosomal recessive 59UniProt
Pathogenic Variants2
NM_005536.4(IMPA1):c.817C>T (p.Arg273Ter)Likely pathogenic
Intellectual disability, autosomal recessive 59
★☆☆☆2021→ Residue 273
NM_005536.4(IMPA1):c.489_493dup (p.Ser165fs)Pathogenic
Intellectual disability, autosomal recessive 59
☆☆☆☆2022→ Residue 165
View on ClinVar ↗
Drug Targets2
LITHIUM CARBONATEApproved
Glycogen synthase kinase-3 inhibitor
bipolar disorder
LITHIUM CITRATEApproved
Glycogen synthase kinase-3 inhibitor
Related Genes
MIOXProtein interaction94%MTM1Protein interaction94%CDIPTProtein interaction92%ISYNA1Protein interaction91%INPP4BProtein interaction91%INPP4AProtein interaction91%
Tissue Expression6 tissues
Heart
100%
Liver
85%
Bone Marrow
78%
Brain
77%
Ovary
31%
Lung
22%
Gene Interaction Network
Click a node to explore
IMPA1MIOXMTM1CDIPTISYNA1INPP4BINPP4A
PROTEIN STRUCTURE
Preparing viewer…
PDB6GIU · 1.39 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.53LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.52 [0.21–1.53]
RankingsWhere IMPA1 stands among ~20K protein-coding genes
  • #7,782of 20,598
    Most Researched59
  • #650of 1,025
    FDA-Approved Drug Targets2
  • #4,410of 5,498
    Most Pathogenic Variants2
  • #15,345of 17,882
    Most Constrained (LOEUF)1.53
Genes detectedIMPA1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
IMPA1-derived inositol maintains stemness in castration-resistant prostate cancer via IMPDH2 activation.
PMID: 39470689
J Exp Med · 2024
1.00
2
IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium.
PMID: 38056909
Life Sci Alliance · 2024
0.90
3
Human myo-inositol monophosphatase 2 rescues the nematode thermotaxis mutant ttx-7 more efficiently than IMPA1: functional and evolutionary considerations of the two mammalian myo-inositol monophosphatase genes.
PMID: 23205734
J Neurochem · 2013
0.80
4
Inositol monophosphatase 1 (IMPA1) promotes triple-negative breast cancer progression through regulating mTOR pathway and EMT process.
PMID: 35796646
Cancer Med · 2023
0.70
5
Emerging role of inositol monophosphatase in cancer.
PMID: 36841024
Biomed Pharmacother · 2023
0.60