INPPL1 Gene (Inositol Polyphosphate Phosphatase Like 1)
SHIP2: A Key Regulator of Phosphoinositide Signaling and Its Role in Opsismodysplasia and Cancer
Gene Information Card
| Symbol | INPPL1 |
|---|---|
| Full Name | Inositol Polyphosphate Phosphatase Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.4 |
| NCBI Gene ID | 3636 ncbi.nlm.nih.gov/gene/3636 |
| Ensembl ID | ENSG00000165458 |
| UniProt ID | O15357 |
| OMIM ID | 600829 |
| HGNC ID | 6080 |
| Aliases | SHIP2, SHIP-2, 51C, INPP5D-like |
Description
The INPPL1 gene encodes SHIP2 (SH2 domain-containing inositol 5-phosphatase 2), a lipid phosphatase that dephosphorylates phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (3,4)-bisphosphate, thereby negatively regulating the PI3K/AKT signaling pathway. SHIP2 is involved in insulin signaling, cytoskeletal organization, and cell proliferation. Loss-of-function mutations in INPPL1 cause opsismodysplasia, a severe skeletal dysplasia. Altered expression and mutations are also implicated in various cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Opsismodysplasia | Loss-of-function mutations in INPPL1 impair SHIP2 phosphatase activity, disrupting PI3K/AKT signaling and skeletal development. | OMIM #258480; ClinVar |
| Breast Cancer | SHIP2 overexpression or gain-of-function mutations may promote cell migration and invasion via altered phosphoinositide signaling. | COSMIC; PubMed studies |
| Type 2 Diabetes | SHIP2 deficiency or reduced activity enhances insulin sensitivity by prolonging PIP3 levels and AKT activation. | OMIM; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 10.2 | Medium |
| Heart | 8.5 | Medium |
| Kidney | 7.1 | Medium |
| Liver | 4.3 | Low |
| Brain | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 12.5 | High expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate expression |
| HepG2 (liver cancer) | 5.2 | Low expression |
| K562 (leukemia) | 6.7 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2174G>A (p.Arg725Gln) | Missense | <0.01% | Loss of phosphatase activity; associated with opsismodysplasia |
| c.1960C>T (p.Arg654Trp) | Missense | <0.01% | Impaired protein stability; opsismodysplasia |
| c.1123_1124del (p.Val375fs) | Frameshift | <0.01% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most INPPL1 mutations in opsismodysplasia are loss-of-function, reducing or abolishing SHIP2 phosphatase activity, leading to dysregulated PI3K/AKT signaling.
Gain of Function (GOF)
Gain-of-function mutations are rare but have been reported in some cancers, enhancing SHIP2 activity and promoting cell migration.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for INPPL1.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-3 | • 4 |
| • 5-trisphosphate 5-phosphatase activity | • 4-bisphosphate 5-phosphatase activity |
| • SH2 domain binding | • negative regulation of phosphatidylinositol 3-kinase signaling |
| • insulin receptor signaling pathway | • cytoskeleton organization |
Pathways
• PI3K/AKT signaling pathway
• Insulin signaling pathway
• Fc gamma R-mediated phagocytosis
• Phosphatidylinositol phosphate metabolism
Protein Summary
SHIP2 is a 1258-amino acid protein containing an N-terminal SH2 domain, a central 5-phosphatase catalytic domain, and C-terminal proline-rich regions. It localizes to the plasma membrane and cytosol, where it hydrolyzes PIP3 to PI(3,4)P2, antagonizing PI3K signaling. SHIP2 also interacts with adaptor proteins like Shc and Grb2, influencing cell adhesion and migration. Its expression is highest in skeletal muscle, heart, and kidney.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INPPL1 Knockout HEK293 Cell Line | EDJ-KQ1658 | Human | 3636 | Details Get a Quote |
| INPPL1 Knockout A-549 Cell Line | EDJ-KQ21413 | Human | 3636 | Details Get a Quote |
| INPPL1 Knockout HCT 116 Cell Line | EDJ-KQ21414 | Human | 3636 | Details Get a Quote |
| INPPL1 Knockout HeLa Cell Line | EDJ-KQ21415 | Human | 3636 | Details Get a Quote |
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