PIK3R5
Phosphoinositide-3-Kinase Regulatory Subunit 5
Gene Information Card
| Symbol | PIK3R5 |
|---|---|
| Full Name | Phosphoinositide-3-Kinase Regulatory Subunit 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 23533 ncbi.nlm.nih.gov/gene/23533 |
| Ensembl ID | ENSG00000141506 |
| UniProt ID | Q8WYR1 |
| OMIM ID | 611317 |
| HGNC ID | 8980 |
| Aliases | p101, PI3K regulatory subunit p101, PIK3R5 |
Description
PIK3R5 (Phosphoinositide-3-Kinase Regulatory Subunit 5) encodes the p101 regulatory subunit of class IB phosphoinositide 3-kinase (PI3K gamma). This subunit is essential for the activation of PI3K gamma by G protein-coupled receptors (GPCRs) in immune cells, mediating chemotaxis, adhesion, and reactive oxygen species production. Mutations in PIK3R5 are associated with primary immunodeficiency, specifically recurrent infections and impaired neutrophil function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 36 (IMD36) | Loss-of-function mutations impair PI3K gamma signaling, leading to defective neutrophil chemotaxis and respiratory burst. | OMIM #616452; ClinVar |
| Recurrent sinopulmonary infections | Impaired immune cell migration and phagocyte function due to reduced PI3K gamma activity. | OMIM #616452; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Lung | 4.1 | Low |
| Whole Blood | 3.8 | Low |
| Lymph Node | 6.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-60 (promyeloblast) | 15.2 | High expression; neutrophil-like differentiation |
| K-562 (lymphoblast) | 2.1 | Low expression |
| THP-1 (monocyte) | 7.8 | Medium expression; macrophage lineage |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1492C>T (p.Arg498Ter) | Nonsense | Rare | Loss of function; truncated protein |
| c.2035G>A (p.Glu679Lys) | Missense | Rare | Impaired GPCR-mediated PI3K activation |
| c.1120_1121del (p.Leu374fs) | Frameshift | Rare | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg498Ter, p.Leu374fs) lead to truncated or absent p101 protein, reducing PI3K gamma activity and impairing immune cell signaling.
Gain of Function (GOF)
No gain-of-function mutations reported in PIK3R5.
Dominant Negative (DN)
No dominant-negative mutations reported in PIK3R5.
View complete mutation data：
Gene Ontology (GO)
| • signal transducer activity (GO:0004871) | • phosphatidylinositol 3-kinase complex (GO:0005942) |
| • phosphatidylinositol 3-kinase regulator activity (GO:0035014) | • positive regulation of GTPase activity (GO:0043547) |
| • leukocyte migration (GO:0050900) |
Pathways
• PI3K-Akt signaling pathway (KEGG hsa04151)
• Chemokine signaling pathway (KEGG hsa04062)
• Fc gamma R-mediated phagocytosis (KEGG hsa04666)
• B cell receptor signaling pathway (KEGG hsa04662)
Protein Summary
The p101 regulatory subunit encoded by PIK3R5 is a 110 kDa protein that binds to the p110 gamma catalytic subunit of PI3K gamma. It mediates the activation of PI3K gamma by G protein-coupled receptors (GPCRs) via interaction with G beta-gamma subunits. p101 is predominantly expressed in hematopoietic cells and is critical for chemotaxis, adhesion, and superoxide production in neutrophils and macrophages. Loss of p101 function leads to primary immunodeficiency characterized by recurrent infections.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIK3R5 Knockout HEK293 Cell Line | EDJ-KQ845 | Human | 23533 | Details Get a Quote |
| PIK3R5 Knockout HCT 116 Cell Line | EDJ-KQ19635 | Human | 23533 | Details Get a Quote |
| PIK3R5 Knockout HeLa Cell Line | EDJ-KQ55760 | Human | 23533 | Details Get a Quote |
| PIK3R5 Knockout A-549 Cell Line | EDJ-KQ64258 | Human | 23533 | Details Get a Quote |
