PIK3R4
Phosphoinositide 3-Kinase Regulatory Subunit 4
Gene Information Card
| Symbol | PIK3R4 |
|---|---|
| Full Name | phosphoinositide-3-kinase regulatory subunit 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q22.1 |
| NCBI Gene ID | 30849 ncbi.nlm.nih.gov/gene/30849 |
| Ensembl ID | ENSG00000196455 |
| UniProt ID | Q99570 |
| OMIM ID | 602610 |
| HGNC ID | 8982 |
| Aliases | VPS15, p150 |
Description
PIK3R4 encodes the regulatory subunit 4 of class III phosphoinositide 3-kinase (PI3K), also known as VPS15. This protein is a serine/threonine kinase that binds to the catalytic subunit PIK3C3 (VPS34) to form the PI3K-III complex, which is essential for autophagy, endosomal trafficking, and vesicle-mediated signaling. PIK3R4 acts as a scaffold and regulatory component, controlling the activity and localization of the PI3K-III complex.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Alzheimer's disease) | Impaired autophagy due to PI3K-III complex dysfunction leads to accumulation of protein aggregates and damaged organelles. | PMID: 25621951; ClinVar |
| Cancer (e.g., breast, colorectal) | Altered PI3K-III signaling affects cell growth, survival, and autophagy; mutations may promote tumorigenesis. | COSMIC; PMID: 23584533 |
| Primary immunodeficiency (e.g., combined immunodeficiency) | Loss-of-function mutations in PIK3R4 disrupt endosomal trafficking and immune cell function. | ClinVar; PMID: 31073079 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 10.5 | Medium |
| Kidney | 11.3 | Medium |
| Heart | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression |
| HeLa | 14.1 | Medium expression |
| MCF7 | 12.6 | Medium expression |
| A549 | 11.9 | Medium expression |
| K562 | 8.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon, likely loss of function |
| c.1234C>T (p.Arg412Trp) | missense | 0.02% | Impaired kinase activity, reduced autophagy |
| c.2567_2568del (p.Gln856fs) | frameshift | <0.01% | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the kinase domain or protein stability lead to impaired PI3K-III complex formation and reduced autophagy.
Gain of Function (GOF)
Not well documented; no recurrent gain-of-function mutations reported in PIK3R4.
Dominant Negative (DN)
Some missense mutations may interfere with wild-type PIK3R4 binding to PIK3C3, reducing complex activity.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • protein kinase activity (GO:0004672) |
| • kinase activity (GO:0016301) | • phosphatidylinositol 3-kinase complex (GO:0034045) |
| • autophagy (GO:0006914) | • endosomal transport (GO:0016197) |
Pathways
• Autophagy - Homo sapiens (hsa04140)
• Phosphatidylinositol signaling system (hsa04070)
• Endocytosis (hsa04144)
Protein Summary
PIK3R4 (VPS15) is a 1358-amino-acid serine/threonine kinase that serves as the regulatory subunit of class III PI3K. It contains an N-terminal kinase domain, HEAT repeats, and WD40 repeats that mediate interactions with PIK3C3 and other proteins. The protein is ubiquitously expressed and localizes to endosomal membranes, where it regulates autophagy, vesicle trafficking, and nutrient signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIK3R4 Knockout HEK293 Cell Line | EDJ-KQ51257 | Human | 30849 | Details Get a Quote |
| PIK3R4 Knockout HeLa Cell Line | EDJ-KQ56159 | Human | 30849 | Details Get a Quote |
| PIK3R4 Knockout A-549 Cell Line | EDJ-KQ64648 | Human | 30849 | Details Get a Quote |
| PIK3R4 Knockout HCT 116 Cell Line | EDJ-KQ73096 | Human | 30849 | Details Get a Quote |
