INPP5E (Inositol Polyphosphate-5-Phosphatase E)
A key regulator of ciliary signaling and phosphoinositide metabolism
Gene Information Card
| Symbol | INPP5E |
|---|---|
| Full Name | Inositol Polyphosphate-5-Phosphatase E |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.3 |
| NCBI Gene ID | 56623 ncbi.nlm.nih.gov/gene/56623 |
| Ensembl ID | ENSG00000140650 |
| UniProt ID | Q9NRR6 |
| OMIM ID | 613037 |
| HGNC ID | 8962 |
| Aliases | CORS1, JBTS1, MORM1, PIPP, phosphatidylinositol-4,5-bisphosphate 5-phosphatase |
Description
INPP5E encodes a 5-phosphatase enzyme that dephosphorylates phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate, regulating phosphoinositide signaling at the primary cilium. It is essential for ciliary membrane composition and Hedgehog signaling. Loss-of-function mutations cause Joubert syndrome and MORM syndrome, both ciliopathies characterized by neurological and developmental defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Joubert syndrome 1 (JBTS1) | Loss of INPP5E function disrupts ciliary phosphoinositide balance, impairing Hedgehog signaling and causing cerebellar vermis hypoplasia, hypotonia, and developmental delay. | OMIM #213300; ClinVar pathogenic variants |
| MORM syndrome (mental retardation, truncal obesity, retinal dystrophy, micropenis) | Defective INPP5E leads to altered ciliary signaling, resulting in syndromic intellectual disability and metabolic abnormalities. | OMIM #610156; case reports |
| Retinitis pigmentosa (non-syndromic) | INPP5E mutations can cause isolated retinal degeneration due to ciliary dysfunction in photoreceptors. | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.9 | Medium |
| Brain (cerebellum) | 12.3 | Medium |
| Kidney | 10.1 | Medium |
| Liver | 6.5 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells |
| SH-SY5Y | 11.7 | Neuroblastoma cells |
| ARPE-19 | 9.4 | Retinal pigment epithelial cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1990C>T (p.Arg664*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1573G>A (p.Gly525Arg) | Missense | Rare | Impaired catalytic activity; reduced ciliary localization |
| c.1180C>T (p.Arg394Trp) | Missense | Rare | Dominant-negative effect in some families |
Mutation functional classification
Loss of Function (LOF)
Most INPP5E mutations are loss-of-function, leading to reduced phosphatase activity and ciliary dysfunction, as seen in Joubert syndrome.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Rare missense variants (e.g., p.Arg394Trp) may act in a dominant-negative manner, interfering with wild-type INPP5E function.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-4 | • 5-bisphosphate 5-phosphatase activity |
| • phosphatidylinositol-3 | • 4 |
| • 5-trisphosphate 5-phosphatase activity | • cilium assembly |
| • Hedgehog signaling pathway | • phosphatidylinositol dephosphorylation |
| • protein localization to cilium |
Pathways
• Phosphoinositide metabolism
• Ciliary signaling
• Hedgehog signaling pathway
Protein Summary
INPP5E is a 644-amino acid protein containing a conserved 5-phosphatase domain and a C-terminal CAAX motif for prenylation, which targets it to the ciliary membrane. It hydrolyzes PI(4,5)P2 and PI(3,4,5)P3, controlling ciliary phosphoinositide composition. Defects in INPP5E impair ciliary function and lead to ciliopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INPP5E Knockout HEK293 Cell Line | EDJ-KQ1655 | Human | 56623 | Details Get a Quote |
| INPP5E Knockout A-549 Cell Line | EDJ-KQ21403 | Human | 56623 | Details Get a Quote |
| INPP5E Knockout HCT 116 Cell Line | EDJ-KQ21404 | Human | 56623 | Details Get a Quote |
| INPP5E Knockout HeLa Cell Line | EDJ-KQ21405 | Human | 56623 | Details Get a Quote |
| INPP5E Knockout HAP1 Cell Line | EDC08129 | Human | 56623 | Details Get a Quote |
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