INPP5D (SHIP1) Gene
Inositol Polyphosphate-5-Phosphatase D: A Key Regulator of Immune Signaling and Hematopoiesis
Gene Information Card
| Symbol | INPP5D |
|---|---|
| Full Name | Inositol Polyphosphate-5-Phosphatase D |
| Gene Type | Protein coding |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 3635 ncbi.nlm.nih.gov/gene/3635 |
| Ensembl ID | ENSG00000168918 |
| UniProt ID | Q92835 |
| OMIM ID | 601582 |
| HGNC ID | 6079 |
| Aliases | SHIP, SHIP1, p150Ship, SIP-145 |
Description
INPP5D encodes the SH2 domain-containing inositol 5'-phosphatase 1 (SHIP1), a key negative regulator of phosphoinositide 3-kinase (PI3K) signaling in hematopoietic cells. The protein hydrolyzes phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (3,4)-bisphosphate, thereby attenuating downstream AKT activation. SHIP1 modulates immune receptor signaling, cell proliferation, survival, and migration. Loss-of-function mutations and altered expression are implicated in hematologic malignancies, inflammatory disorders, and Alzheimer disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | Reduced INPP5D expression in microglia leads to impaired PIP3 hydrolysis, promoting neuroinflammation and amyloid-beta accumulation. | ClinVar, OMIM |
| Acute myeloid leukemia | Somatic mutations and deletions of INPP5D result in loss of SHIP1 function, enhancing PI3K/AKT signaling and leukemic cell survival. | COSMIC, NCBI |
| B-cell lymphoma | Epigenetic silencing or mutation of INPP5D contributes to constitutive PI3K pathway activation in B-cell malignancies. | COSMIC, OMIM |
| Inflammatory bowel disease | Polymorphisms in INPP5D are associated with altered immune regulation and increased susceptibility to Crohn disease. | NCBI, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lymph node | 9.2 | Medium |
| Whole blood | 8.1 | Low |
| Brain (cortex) | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HL-60 (promyeloblast) | 14.1 | High expression |
| THP-1 (monocyte) | 12.7 | Medium expression |
| HEK 293 (embryonic kidney) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1849C>T (p.Arg617*) | Nonsense | <1% in AML | Loss of function; truncated protein lacking catalytic domain |
| c.2155_2156del (p.Glu719fs) | Frameshift | <1% in lymphoma | Loss of function; premature stop codon |
| c.1123G>A (p.Gly375Arg) | Missense | <0.1% in Alzheimer disease | Reduced phosphatase activity; impaired PIP3 hydrolysis |
| c.1471A>G (p.Asn491Asp) | Missense | <0.1% in IBD | Altered protein stability; decreased SHIP1 expression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg617*, p.Glu719fs) produce truncated, non-functional SHIP1, leading to unchecked PI3K/AKT signaling and increased cell survival in hematologic cancers.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in INPP5D.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly375Arg) may produce a partially active protein that interferes with wild-type SHIP1 function, though dominant-negative effects are not well established.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-3 | • 4 |
| • 5-trisphosphate 5-phosphatase activity | • 4-bisphosphate 5-phosphatase activity |
| • SH2 domain binding | • signal transduction |
| • negative regulation of cell proliferation | • negative regulation of phosphatidylinositol 3-kinase signaling |
| • immune system process | • hematopoietic progenitor cell differentiation |
Pathways
• PI3K/AKT signaling pathway
• Fc gamma receptor-mediated phagocytosis
• B cell receptor signaling pathway
• T cell receptor signaling pathway
• Fc epsilon RI signaling pathway
Protein Summary
SHIP1 (SH2 domain-containing inositol 5'-phosphatase 1) is a 145 kDa cytoplasmic protein predominantly expressed in hematopoietic cells. It contains an N-terminal SH2 domain, a central 5-phosphatase catalytic domain, and C-terminal proline-rich and NPXY motifs. SHIP1 dephosphorylates PIP3 at the 5' position, generating PI(3,4)P2, thereby antagonizing PI3K-dependent AKT activation. Through this activity, SHIP1 negatively regulates growth factor and immune receptor signaling, controlling cell survival, proliferation, and differentiation. Loss of SHIP1 function contributes to leukemogenesis and neuroinflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INPP5D Knockout HEK293 Cell Line | EDJ-KQ1657 | Human | 3635 | Details Get a Quote |
| INPP5D Knockout HeLa Cell Line | EDJ-KQ53666 | Human | 3635 | Details Get a Quote |
| INPP5D Knockout A-549 Cell Line | EDJ-KQ62140 | Human | 3635 | Details Get a Quote |
| INPP5D Knockout HCT 116 Cell Line | EDJ-KQ70630 | Human | 3635 | Details Get a Quote |
