Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate cytoskeletal functions, membrane trafficking, and receptor signaling by recruiting protein complexes to cell- and endosomal-membranes. Humans have multiple PtdIns proteins that differ by the degree and position of phosphorylation of the inositol ring. This gene encodes an enzyme (PIKfyve; also known as phosphatidylinositol-3-phosphate 5-kinase type III or PIPKIII) that phosphorylates the D-5 position in PtdIns and phosphatidylinositol-3-phosphate (PtdIns3P) to make PtdIns5P and PtdIns(3,5)biphosphate. The D-5 position also can be phosphorylated by type I PtdIns4P-5-kinases (PIP5Ks) that are encoded by distinct genes and preferentially phosphorylate D-4 phosphorylated PtdIns. In contrast, PIKfyve preferentially phosphorylates D-3 phosphorylated PtdIns. In addition to being a lipid kinase, PIKfyve also has protein kinase activity. PIKfyve regulates endomembrane homeostasis and plays a role in the biogenesis of endosome carrier vesicles from early endosomes. The protein plays a key role in cell entry of ebola virus and SARS-CoV-2 by endocytosis Mutations in this gene cause corneal fleck dystrophy (CFD); an autosomal dominant disorder characterized by numerous small white flecks present in all layers of the corneal stroma. Histologically, these flecks appear to be keratocytes distended with lipid and mucopolysaccharide filled intracytoplasmic vacuoles. [provided by RefSeq, Jul 2021]
Transcription factors with Perturb-seq knockdown data for PIKFYVE. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = PIKFYVE upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of PIKFYVE, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr2:207,970,009–207,971,155 | 295.7 kb | Distal (>10kb) Multiome | 256 | |
| chr2:208,025,250–208,025,873 | 240.7 kb | Distal (>10kb) Multiome | 1046 | |
| chr2:208,112,378–208,113,769 | 153.1 kb | Distal (>10kb) Multiome | 285 | |
| chr2:208,124,049–208,124,760 | 141.9 kb | Distal (>10kb) Multiome | 140 | |
| chr2:208,142,720–208,143,849 | 122.9 kb | Distal (>10kb) Multiome | 333 | |
| chr2:208,215,744–208,216,551 | 50.1 kb | Distal (>10kb) Multiome | 25 | |
| chr2:208,253,738–208,255,989 | 12.0 kb | Distal (>10kb) Multiome | 1085 | |
| chr2:208,265,281–208,266,835 | 48 bp | At TSS Multiome | 1005 | |
| chr2:208,267,505–208,268,088 | 1.6 kb | Proximal (<10kb) Multiome | 169 | |
| chr2:208,317,884–208,318,936 | 52.1 kb | Distal (>10kb) Multiome | 106 | |
| chr2:208,406,386–208,407,453 | 140.7 kb | Distal (>10kb) Multiome | 324 |
Genomic view of the PIKFYVE locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.