PIK3R3 Gene: Phosphoinositide-3-Kinase Regulatory Subunit 3
A key regulatory subunit of PI3K, implicated in cancer, insulin signaling, and immune regulation.
Gene Information Card
| Symbol | PIK3R3 |
|---|---|
| Full Name | phosphoinositide-3-kinase regulatory subunit 3 |
| Gene Type | protein coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 8503 ncbi.nlm.nih.gov/gene/8503 |
| Ensembl ID | ENSG00000117461 |
| UniProt ID | Q92569 |
| OMIM ID | 603157 |
| HGNC ID | 8979 |
| Aliases | p55, p55PIK, P55-GAMMA |
Description
PIK3R3 encodes the regulatory subunit p55γ of phosphoinositide 3-kinase (PI3K). This subunit binds to the catalytic p110 subunit and mediates signal transduction downstream of receptor tyrosine kinases. It is involved in various cellular processes including proliferation, survival, and metabolism. PIK3R3 is overexpressed in several cancers and contributes to tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of PIK3R3 enhances PI3K/AKT signaling, promoting cell proliferation and survival. | COSMIC: high expression in breast, colorectal, and lung cancers; ClinVar: somatic mutations reported. |
| Type 2 diabetes | Altered PIK3R3 expression affects insulin signaling pathway, contributing to insulin resistance. | UniProt: involved in insulin receptor signaling; OMIM: associated with insulin resistance. |
| Immunodeficiency | Defects in PI3K signaling due to PIK3R3 mutations may impair immune cell function. | ClinVar: rare variants linked to primary immunodeficiency. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Breast | 8.7 | Low |
| Colon | 15.2 | Medium |
| Kidney | 10.5 | Medium |
| Liver | 6.1 | Low |
| Lung | 9.8 | Low |
| Muscle | 4.2 | Low |
| Ovary | 11.4 | Medium |
| Pancreas | 7.3 | Low |
| Skin | 5.6 | Low |
| Spleen | 18.9 | High |
| Stomach | 8.1 | Low |
| Testis | 20.5 | High |
| Thyroid | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 14.5 | High expression |
| A549 (lung cancer) | 11.2 | Moderate expression |
| HCT116 (colorectal cancer) | 16.8 | High expression |
| HEK293 (embryonic kidney) | 9.3 | Low expression |
| K562 (leukemia) | 22.1 | Very high expression |
| HepG2 (liver cancer) | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1255G>A (p.Gly419Arg) | Missense | 0.5% (COSMIC) | Potential gain-of-function; increased AKT phosphorylation. |
| c.1672C>T (p.Arg558Trp) | Missense | 0.2% (COSMIC) | Loss-of-function; reduced PI3K activity. |
| c.2146A>G (p.Ile716Val) | Missense | 0.1% (COSMIC) | Unknown effect; located in SH2 domain. |
| c.1024C>T (p.Arg342Ter) | Nonsense | 0.05% (COSMIC) | Truncated protein; likely loss-of-function. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce PI3K activity, often in the kinase-binding domain, leading to impaired signaling.
Gain of Function (GOF)
Mutations that enhance PI3K/AKT signaling, often in the SH2 domain, promoting oncogenic transformation.
Dominant Negative (DN)
Mutations that produce a truncated p55γ that sequesters p110 but fails to activate it, blocking normal PI3K signaling.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004871 (signal transducer activity) | • GO:0005515 (protein binding) |
| • GO:0016301 (kinase activity) | • GO:0046934 (phosphatidylinositol-4 |
| • 5-bisphosphate 3-kinase activity) | • GO:0008289 (lipid binding) |
| • GO:0005737 (cytoplasm) | • GO:0005886 (plasma membrane) |
| • GO:0005829 (cytosol) |
Pathways
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Insulin signaling pathway (KEGG: hsa04910)
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)
• T cell receptor signaling pathway (KEGG: hsa04660)
• ErbB signaling pathway (KEGG: hsa04012)
Protein Summary
The PIK3R3 protein (p55γ) is a regulatory subunit of class IA PI3K. It contains an N-terminal SH2 domain and a C-terminal SH2 domain flanking a p110-binding region. p55γ binds to the p110 catalytic subunit and mediates recruitment to phosphorylated tyrosine residues on activated receptors. This interaction activates PI3K, leading to the production of PIP3 and subsequent activation of AKT. p55γ is expressed in various tissues, with high levels in spleen and testis. It plays a critical role in cell growth, survival, and metabolism. Aberrant expression or mutations are linked to cancer and metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIK3R3 Knockout HEK293 Cell Line | EDJ-KQ1191 | Human | 8503 | Details Get a Quote |
| PIK3R3 Knockout A-549 Cell Line | EDJ-KQ20485 | Human | 8503 | Details Get a Quote |
| PIK3R3 Knockout HCT 116 Cell Line | EDJ-KQ20486 | Human | 8503 | Details Get a Quote |
| PIK3R3 Knockout HeLa Cell Line | EDJ-KQ20487 | Human | 8503 | Details Get a Quote |
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