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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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INPP5J
inositol polyphosphate-5-phosphatase J
Chromosome 22 · 22q12.2
NCBI Gene: 27124Ensembl: ENSG00000185133.15HGNC: HGNC:8956UniProt: B4DF95
17PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcytoplasmruffleneuron projectionneurodegenerative diseaseAbnormality of the skeletal systemmelanomaneural tube defect
✦AI Summary

INPP5J (inositol polyphosphate-5-phosphatase J) is a lipid phosphatase that catalyzes the removal of 5-phosphate from phosphoinositides, converting phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) 1. This enzymatic activity suppresses PI3K/AKT signaling, a key oncogenic pathway 2. INPP5J functions as a tumor suppressor across multiple cancer types. In pancreatic cancer, INPP5J expression is markedly reduced, and its overexpression inhibits cell proliferation, invasion, and migration; conversely, INPP5J knockdown promotes these malignant behaviors 3. In breast cancer, INPP5J (also called PIPP) cooperatively suppresses AKT signaling with PTEN, and combined loss of both phosphatases is associated with enhanced cell proliferation and reduced patient survival 4. In ovarian cancer, the microRNA miR-661 promotes proliferation by directly repressing INPP5J expression and subsequently activating AKT signaling 5. INPP5J degradation can be promoted through ubiquitination by E3 ligase PELI1, linking protein stability regulation to cancer progression 3. Additionally, INPP5J has been identified as a potential tumor antigen in lung adenocarcinoma, with expression correlating to immune cell infiltration patterns 6. Its dysregulation appears central to multiple malignancies.

Sources cited
1
INPP5J is a tumor suppressor in pancreatic cancer; its overexpression inhibits proliferation and invasion while PELI1 promotes its ubiquitination-mediated degradation
PMID: 38685520
2
INPP5J (PIPP) dephosphorylates PtdIns(3,4,5)P3 and cooperatively suppresses AKT signaling with PTEN; combined loss is associated with breast cancer progression
PMID: 41408399
3
INPP5J (PIPP) hydrolyzes PtdIns(3,4,5)P3 to PtdIns(3,4)P2, functioning as a phosphoinositide phosphatase that suppresses PI3K/AKT signaling in cancer
PMID: 28082369
4
5-phosphatases including INPP5J inhibit PI3K-driven AKT signaling and have been identified as putative tumor suppressors in melanoma and breast cancer
PMID: 26862211
5
miR-661 promotes ovarian cancer cell proliferation by directly repressing INPP5J expression and activating AKT pathway signaling
PMID: 26282217
6
INPP5J is identified as a potential tumor antigen in lung adenocarcinoma with expression correlating to immune cell infiltration
PMID: 36809467
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.26Weak
Abnormality of the skeletal systemOpen Targets
0.16Weak
melanomaOpen Targets
0.08Suggestive
neural tube defectOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.05Suggestive
Isolated anophthalmia - microphthalmiaOpen Targets
0.04Suggestive
Microphthalmia - ankyloblepharon - intellectual disabilityOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
respiratory distress syndrome in premature infantsOpen Targets
0.02Suggestive
Crohn's diseaseOpen Targets
0.02Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
oculocerebrorenal syndromeOpen Targets
0.02Suggestive
medulloblastomaOpen Targets
0.02Suggestive
Joubert syndromeOpen Targets
0.01Suggestive
retinitis pigmentosa 1Open Targets
0.01Suggestive
ciliopathyOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IPMKProtein interaction95%INPP1Protein interaction94%ITPK1Protein interaction93%ITPKAProtein interaction93%ITPKBProtein interaction93%MINPP1Protein interaction93%
Tissue Expression6 tissues
Heart
100%
Brain
12%
Lung
7%
Ovary
7%
Bone Marrow
2%
Liver
2%
Gene Interaction Network
Click a node to explore
INPP5JIPMKINPP1ITPK1ITPKAITPKBMINPP1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q15735
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.16LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.95 [0.79–1.16]
RankingsWhere INPP5J stands among ~20K protein-coding genes
  • #15,026of 20,598
    Most Researched17
  • #12,054of 17,882
    Most Constrained (LOEUF)1.16
Genes detectedINPP5J
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PELI1 overexpression contributes to pancreatic cancer progression through upregulating ubiquitination-mediated INPP5J degradation.
PMID: 38685520
Cell Signal · 2024
1.00
2
Non-redundant roles of the phosphoinositide phosphatases PTEN and PIPP in PI3K/AKT signaling in breast cancer.
PMID: 41408399
Commun Biol · 2025
0.90
3
Regulation of PI3K effector signalling in cancer by the phosphoinositide phosphatases.
PMID: 28082369
Biosci Rep · 2017
0.80
4
Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases.
PMID: 26862211
Biochem Soc Trans · 2016
0.70
5
A germline HLTF mutation in familial MDS induces DNA damage accumulation through impaired PCNA polyubiquitination.
PMID: 30696947
Leukemia · 2019
0.60