PI4KA Gene: Phosphatidylinositol 4-Kinase Alpha
Essential regulator of phosphatidylinositol 4-phosphate synthesis and cellular signaling
Gene Information Card
| Symbol | PI4KA |
|---|---|
| Full Name | Phosphatidylinositol 4-kinase alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 5297 ncbi.nlm.nih.gov/gene/5297 |
| Ensembl ID | ENSG00000100220 |
| UniProt ID | P42356 |
| OMIM ID | 600286 |
| HGNC ID | 8983 |
| Aliases | PI4K-ALPHA, PI4KIIIα, PIK4CA, PI4K230 |
Description
PI4KA encodes the alpha catalytic subunit of phosphatidylinositol 4-kinase (PI4K), which catalyzes the phosphorylation of phosphatidylinositol to phosphatidylinositol 4-phosphate (PI4P). PI4P is a key lipid signaling molecule and precursor for higher phosphoinositides. PI4KA is essential for Golgi-to-plasma membrane trafficking, plasma membrane PI4P pools, and cellular signaling. Mutations in PI4KA are associated with neurological disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual developmental disorder with spasticity and white matter abnormalities | Loss-of-function mutations impair PI4P synthesis, disrupting membrane trafficking and neuronal function | ClinVar, OMIM #616531 |
| PI4KA-related polymicrogyria with or without vascular anomalies | Biallelic missense variants reduce kinase activity, affecting cortical development | ClinVar, OMIM #619621 |
| Colorectal cancer | Somatic mutations and copy number alterations may alter PI4P signaling, promoting tumor growth | COSMIC |
| Breast cancer | Amplification and overexpression of PI4KA observed in some subtypes | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 14.2 | High |
| Testis | 11.8 | High |
| Lung | 8.5 | Medium |
| Liver | 6.3 | Medium |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.4 | Embryonic kidney, high expression |
| HeLa | 10.1 | Cervical carcinoma, moderate |
| HepG2 | 7.8 | Hepatocellular carcinoma, moderate |
| SH-SY5Y | 15.3 | Neuroblastoma, high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.619G>A (p.Gly207Arg) | Missense | Rare | Reduced kinase activity, associated with neurological disease |
| c.2782C>T (p.Arg928Trp) | Missense | Rare | Loss of function, linked to polymicrogyria |
| c.3325G>A (p.Glu1109Lys) | Missense | Rare | Impaired PI4P production, neurological phenotype |
| c.1234_1235insA (p.Thr412Asnfs*3) | Frameshift | Rare | Truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic mutations reduce or abolish PI4KA kinase activity, leading to decreased PI4P levels and disrupted membrane trafficking.
Gain of Function (GOF)
Not well documented; some cancer-associated amplifications may increase activity but functional evidence is limited.
Dominant Negative (DN)
Not established for PI4KA; recessive inheritance pattern is typical.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Phosphatidylinositol phosphate metabolism (Reactome: R-HSA-1483255)
• PI4P synthesis at the Golgi membrane (Reactome: R-HSA-1483226)
• Signaling by PTK6 (Reactome: R-HSA-8848021)
Protein Summary
PI4KA (phosphatidylinositol 4-kinase alpha) is a 230 kDa lipid kinase that phosphorylates phosphatidylinositol at the D4 position of the inositol ring to generate PI4P. It localizes primarily to the Golgi apparatus and plasma membrane, where it regulates membrane trafficking, lipid signaling, and cell growth. The protein contains a lipid kinase domain and is essential for embryonic development and neuronal function.
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