PIK3R6 Gene

PIK3R6 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PIK3R6 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PIK3R6</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Phosphoinositide-3-Kinase Regulatory Subunit 6</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>p101, p84, PI3Kgamma</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17p13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>27137</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>607270</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000110676</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NRA8</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

PIK3R6 (Phosphoinositide-3-Kinase Regulatory Subunit 6) encodes the p101 regulatory subunit of class I phosphoinositide 3-kinases (PI3Ks). While initially characterized in immune cells, emerging research reveals important functions in neuronal survival, synaptic plasticity, and neurodegenerative disease pathogenesis. [@hawkins2015]

Overview

PIK3R6 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PIK3R6 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PIK3R6</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Phosphoinositide-3-Kinase Regulatory Subunit 6</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>p101, p84, PI3Kgamma</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17p13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>27137</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>607270</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000110676</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NRA8</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

PIK3R6 (Phosphoinositide-3-Kinase Regulatory Subunit 6) encodes the p101 regulatory subunit of class I phosphoinositide 3-kinases (PI3Ks). While initially characterized in immune cells, emerging research reveals important functions in neuronal survival, synaptic plasticity, and neurodegenerative disease pathogenesis. [@hawkins2015]

Overview

PIK3R6 is located on chromosome 17p13.1 and encodes the p101 (also known as p84) regulatory subunit of PI3K. The gene is catalogued as NCBI Gene ID 27137 and OMIM 607270. p101 forms heterodimers with PI3K catalytic subunits (p110γ) to create functional PI3K complexes that generate phosphatidylinositol-3,4,5-trisphosphate (PIP3). [@vanhaesebroeck2010]

Gene Information

Protein Structure and Function

PIK3R6 encodes the p101 regulatory subunit:

• SH2 domains: Two src homology 2 domains for phosphotyrosine binding
• iSH2 domain: Inter-SH2 domain for dimerization with catalytic subunit
• p110γ binding: Forms heterodimer with PI3K catalytic subunit p110γ
• Membrane recruitment: Mediates localization to plasma membrane

Normal Physiological Functions

Expression Pattern

PIK3R6 shows cell-type specific expression:

• Neurons: Moderate expression in cortical and hippocampal neurons
• [Microglia](/cell-types/microglia-neuroinflammation): High expression in activated microglia
• [Astrocytes](/entities/astrocytes): Detectable expression in astrocytes
• Oligodendrocytes: Low expression in oligodendrocyte lineage cells
• Immune cells: Highest expression in macrophages and neutrophils

Disease Associations

Alzheimer's Disease

PI3K/Akt signaling is critically involved in AD pathogenesis:

• [Amyloid-beta](/proteins/amyloid-beta) toxicity: PI3K/Akt activation protects neurons from Aβ-induced [apoptosis](/entities/apoptosis)
• [Tau](/proteins/tau) phosphorylation: Akt regulates tau kinases ([GSK-3β](/entities/gsk3-beta), CDK5) affecting phosphorylation
• Synaptic dysfunction: PI3K signaling regulates synaptic plasticity and memory
• Neuroinflammation: Microglial PI3Kγ contributes to neuroinflammatory responses
• Therapeutic potential: PI3K modulators may protect against AD pathology

Parkinson's Disease

• Dopaminergic neuron survival: PI3K/Akt pathway supports SNc neuron viability
• Mitophagy: PI3K signaling regulates mitochondrial quality control
• Neuroinflammation: Microglial PI3Kγ promotes neuroinflammation in PD
• LRRK2 interactions: PIK3R6 may interact with LRRK2 pathogenic variants
• Therapeutic targeting: PI3K inhibitors/modulators for PD treatment

Amyotrophic Lateral Sclerosis

• Motor neuron survival: PI3K/Akt promotes motor neuron viability
• Glial activation: Astrocytic and microglial PI3K contributes to neuroinflammation
• Axonal transport: PI3K signaling regulates axonal transport machinery
• Protein aggregation: PI3K dysregulation affects [autophagy](/entities/autophagy) of protein aggregates

Other Neurological Disorders

• Multiple sclerosis: PI3K in immune cell migration across [blood-brain barrier](/entities/blood-brain-barrier)
• Stroke: PI3K/Akt mediates ischemic preconditioning and neuroprotection
• Huntington's disease: PI3K signaling regulates mutant [huntingtin](/proteins/huntingtin) toxicity
• Frontotemporal dementia: PI3K dysregulation in tauopathies
• Psychiatric disorders: PI3K signaling in mood disorders and schizophrenia

Therapeutic Implications

PI3K signaling pathways represent important therapeutic targets:

Interacting Proteins

PIK3R6 interacts with several key proteins:

• p110γ (PIK3CG): Catalytic subunit of class IB PI3K
• Akt1/PKB: Downstream effector kinase
• GSK-3β: Tau kinase regulated by PI3K/Akt
• [mTOR](/mechanisms/mtor-signaling-pathway): Downstream regulator of cell growth and autophagy
• PTEN: Negative regulator of PI3K/Akt signaling

Signaling Pathways

PIK3R6 participates in critical signaling cascades:

Research Tools

• Knockout mice: Pik3r6-/- mice show immune cell migration defects
• Conditional KO mice: Cell-type specific deletion for neuronal studies
• Pharmacological tools: PI3K inhibitors (wortmannin, LY294002), Akt inhibitors
• AAV vectors: For neuronal overexpression or knockdown

Summary

PIK3R6 encodes the p101 regulatory subunit of class IB PI3K, which plays essential roles in neuronal survival, synaptic plasticity, and neuroinflammation. PI3K/Akt signaling dysfunction contributes to Alzheimer's disease, Parkinson's disease, ALS, and other neurodegenerative disorders. Modulating PIK3R6 and downstream PI3K pathways represents a promising therapeutic strategy for neuroprotection. [@zhang2023]

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [Ensembl: ENSG00000110676](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110676)

References