PIKFYVE: Phosphoinositide Kinase, FYVE-Type Containing
A key regulator of endosomal trafficking and phosphatidylinositol 3,5-bisphosphate synthesis, implicated in neurodegeneration and cancer.
Gene Information Card
| Symbol | PIKFYVE |
|---|---|
| Full Name | Phosphoinositide Kinase, FYVE-Type Containing |
| Gene Type | Protein coding |
| Chromosomal Location | 2q34 |
| NCBI Gene ID | 200576 ncbi.nlm.nih.gov/gene/200576 |
| Ensembl ID | ENSG00000143442 |
| UniProt ID | Q9Y2I7 |
| OMIM ID | 609414 |
| HGNC ID | 23785 |
| Aliases | CFTD, PIP5K3, MGC40405 |
Description
The PIKFYVE gene encodes a large zinc finger protein with both lipid kinase and protein kinase activities. It is primarily involved in the synthesis of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a critical signaling lipid that regulates endosomal trafficking, autophagy, and vesicle formation. PIKFYVE is essential for cellular homeostasis and its dysfunction is linked to various diseases, including neurodegenerative disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease, type 4J (CMT4J) | Loss-of-function mutations lead to reduced PI(3,5)P2 levels, impairing endosomal trafficking in peripheral nerves, causing demyelination and axonal degeneration. | ClinVar, OMIM |
| Amyotrophic lateral sclerosis (ALS) | Rare variants in PIKFYVE may contribute to motor neuron degeneration through disrupted autophagy and endosomal trafficking, leading to protein aggregation. | ClinVar, literature |
| Cancer (various types) | Altered PIKFYVE expression or activity can affect cell growth and survival pathways; inhibition of PIKFYVE has been shown to suppress tumor growth in some models. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.4 | Low |
| Testis | 12.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | High expression |
| A549 | 12.3 | Moderate expression |
| MCF7 | 10.8 | Moderate expression |
| HEK293 | 14.2 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4718G>A (p.Arg1573His) | Missense | Rare | Reduced kinase activity, associated with CMT4J |
| c.5737C>T (p.Arg1913Ter) | Nonsense | Rare | Truncated protein, loss of function, linked to ALS |
| c.1234A>G (p.Lys412Glu) | Missense | Somatic | Potential gain-of-function in cancer, increased PI(3,5)P2 production |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations reduce or abolish PIKFYVE kinase activity, leading to decreased PI(3,5)P2 levels, impaired endosomal trafficking, and neurodegeneration.
Gain of Function (GOF)
Gain-of-function mutations may increase PIKFYVE activity, potentially promoting cell proliferation and survival in cancer contexts.
Dominant Negative (DN)
Some mutations may exert dominant-negative effects by interfering with the normal protein's function, though this is less characterized.
View complete mutation data：
Gene Ontology (GO)
| • 1-phosphatidylinositol-3-phosphate 5-kinase activity | • ATP binding |
| • Protein kinase activity | • Zinc ion binding |
| • Endosome membrane | • Cytoplasm |
| • Autophagosome | • Phosphatidylinositol metabolic process |
| • Endosomal transport | • Autophagy |
Pathways
• Phosphatidylinositol phosphate metabolism
• Endosomal trafficking
• Autophagy
Protein Summary
The PIKFYVE protein is a 237 kDa enzyme that localizes to endosomal membranes. It contains a FYVE zinc finger domain that binds phosphatidylinositol 3-phosphate, targeting the protein to endosomes. PIKFYVE phosphorylates phosphatidylinositol 3-phosphate to generate PI(3,5)P2, which is crucial for endosome maturation, vesicle budding, and autophagy. The protein also has serine/threonine kinase activity, though its substrates are less defined. Mutations in PIKFYVE are associated with neurological disorders and cancer, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIKFYVE Knockout SRA01/04 Cell Line | EDJ-KQ66 | Human | 200576 | Details Get a Quote |
| PIKFYVE Knockout HEK293 Cell Line | EDJ-KQ1660 | Human | 200576 | Details Get a Quote |
| PIKFYVE Knockout A-549 Cell Line | EDJ-KQ21419 | Human | 200576 | Details Get a Quote |
| PIKFYVE Knockout HCT 116 Cell Line | EDJ-KQ21420 | Human | 200576 | Details Get a Quote |
| PIKFYVE Knockout HeLa Cell Line | EDJ-KQ21421 | Human | 200576 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
