PIP5K1C Gene (Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Gamma)
Key regulator of phosphoinositide signaling, implicated in hereditary spastic paraplegia and cancer.
Gene Information Card
| Symbol | PIP5K1C |
|---|---|
| Full Name | phosphatidylinositol-4-phosphate 5-kinase type 1 gamma |
| Gene Type | protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 8396 ncbi.nlm.nih.gov/gene/8396 |
| Ensembl ID | ENSG00000186111 |
| UniProt ID | O60331 |
| OMIM ID | 606102 |
| HGNC ID | 8996 |
| Aliases | LCCS3, PIP5K1-gamma, PIP5Kgamma, KIAA0277 |
Description
The PIP5K1C gene encodes phosphatidylinositol-4-phosphate 5-kinase type 1 gamma, an enzyme that catalyzes the phosphorylation of phosphatidylinositol-4-phosphate (PI4P) to generate phosphatidylinositol-4,5-bisphosphate (PIP2), a critical lipid second messenger. PIP2 is involved in various cellular processes including signal transduction, cytoskeletal organization, vesicular trafficking, and cell adhesion. Mutations in PIP5K1C are associated with lethal congenital contracture syndrome 3 (LCCS3) and hereditary spastic paraplegia (SPG80). Altered expression has been observed in several cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lethal congenital contracture syndrome 3 (LCCS3) | Loss-of-function mutations (e.g., p.Pro48Leu) impair PIP2 synthesis, leading to defective motor neuron development and severe contractures. | OMIM #606102; ClinVar |
| Hereditary spastic paraplegia (SPG80) | Missense mutations (e.g., p.Arg273His) disrupt enzyme activity, affecting axonal transport and causing progressive spasticity. | OMIM #606102; ClinVar |
| Cancer (various types) | Overexpression or altered splicing (e.g., PIP5K1C-α/β isoforms) enhances PIP2 production, promoting cell migration and invasion in breast, lung, and colorectal cancers. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High (nTPM ~ 30) | Highest expression in cerebellum and cerebral cortex |
| Lung | Moderate (nTPM ~ 15) | Expressed in alveolar cells |
| Kidney | Moderate (nTPM ~ 12) | Present in renal tubules |
| Liver | Low (nTPM ~ 5) | Minimal expression |
| Heart | Low (nTPM ~ 4) | Weak expression in cardiac muscle |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | High | Strong expression; used in functional studies |
| A549 (lung cancer) | Moderate | Expression correlates with invasive phenotype |
| MCF7 (breast cancer) | Moderate | Overexpression linked to migration |
| HEK293 (embryonic kidney) | High | Commonly used for recombinant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro48Leu | Missense | Rare (found in LCCS3 families) | Loss of function; reduced PIP2 synthesis |
| p.Arg273His | Missense | Rare (SPG80) | Loss of function; impaired kinase activity |
| p.Gly344Ser | Missense | Somatic (COSMIC) | Likely gain of function; increased PIP2 production in tumors |
| c.1234_1235insA | Frameshift | Somatic (COSMIC) | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Pro48Leu and p.Arg273His reduce or abolish kinase activity, leading to decreased PIP2 levels. This impairs neuronal development and axonal maintenance, causing LCCS3 and SPG80.
Gain of Function (GOF)
Somatic mutations like p.Gly344Ser may increase enzyme activity, elevating PIP2 levels and promoting oncogenic signaling, cell migration, and invasion.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by dimerizing with wild-type protein, reducing overall PIP2 production, though this is not well-documented for PIP5K1C.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-4-phosphate 5-kinase activity | • ATP binding |
| • phosphatidylinositol binding | • plasma membrane |
| • cytosol | • actin cytoskeleton organization |
| • phosphatidylinositol biosynthetic process | • signal transduction |
Pathways
• Phosphatidylinositol signaling system
• Fc gamma R-mediated phagocytosis
• Regulation of actin cytoskeleton
• VEGF signaling pathway
Protein Summary
The PIP5K1C protein (UniProt O60331) is a 668-amino acid enzyme with an N-terminal lipid kinase domain and a C-terminal region that mediates membrane localization. It exists in multiple splice isoforms (α, β, γ) with distinct tissue distributions. The enzyme primarily converts PI4P to PIP2 at the plasma membrane, regulating processes such as clathrin-mediated endocytosis, cell adhesion, and focal adhesion dynamics. Its activity is regulated by phosphorylation and interaction with small GTPases. Mutations affecting its function lead to neurological disorders, while overexpression in cancer promotes metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIP5K1C Knockout HEK293 Cell Line | EDJ-KQ1650 | Human | 23396 | Details Get a Quote |
| PIP5K1C Knockout A-549 Cell Line | EDJ-KQ21390 | Human | 23396 | Details Get a Quote |
| PIP5K1C Knockout HCT 116 Cell Line | EDJ-KQ21391 | Human | 23396 | Details Get a Quote |
| PIP5K1C Knockout HeLa Cell Line | EDJ-KQ21392 | Human | 23396 | Details Get a Quote |
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