PLA2G6 — Phospholipase A2 Group VI

PLA2G6 — Phospholipase A2 Group VI

Introduction

Pla2G6 — Phospholipase A2 Group Vi is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

PLA2G6 — Phospholipase A2 Group VI

Introduction

Pla2G6 — Phospholipase A2 Group Vi is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

PLA2G6 (Phospholipase A2 Group VI), also known as iPLA2-VI or iPLA2, is a calcium-independent phospholipase that hydrolyzes the sn-2 position of phospholipids to release fatty acids and lysophospholipids. Located on chromosome 22q13.1, this gene encodes a 752-amino acid protein predominantly expressed in the brain, particularly in regions vulnerable to neurodegeneration["@mancuso2014"].

PLA2G6 belongs to the group VI of phospholipases A2, which are characterized by their lack of calcium dependence for catalytic activity. The enzyme plays important roles in membrane phospholipid remodeling, fatty acid signaling, and the generation of bioactive lipid mediators. In [neurons](/entities/neurons), PLA2G6 is involved in regulating membrane fluidity, synaptic function, and responses to oxidative stress["@phillis2013"].

Mutations in PLA2G6 cause a spectrum of neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD), PLAN (PLA2G6-associated neurodegeneration), and early-onset Parkinson's disease. These conditions share features of progressive motor and cognitive decline, reflecting the protein's essential role in neuronal survival["@shi2011"].

— Phospholipase A2 Group VI

<div class="infobox infobox-gene">
<div class="infobox-header">Gene Information</div>
<div class="infobox-row"><strong>Gene Symbol</strong></div>
<div class="infobox-row">PLA2G6</div>
<div class="infobox-row"><strong>Full Name</strong></div>
<div class="infobox-row">Phospholipase A2 Group VI (iPLA2-VIA)</div>
<div class="infobox-row"><strong>Chromosomal Location</strong></div>
<div class="infobox-row">22q13.1</div>
<div class="infobox-row"><strong>NCBI Gene ID</strong></div>
<div class="infobox-row">[NCBI Gene: 503538](https://www.ncbi.nlm.nih.gov/gene/503538)</div>
<div class="infobox-row"><strong>OMIM</strong></div>
<div class="infobox-row">[OMIM: 603604](https://www.omim.org/entry/603604)</div>
<div class="infobox-row"><strong>Ensembl ID</strong></div>
<div class="infobox-row">ENSG00000156467</div>
<div class="infobox-row"><strong>UniProt ID</strong></div>
<div class="infobox-row">[O60733](https://www.uniprot.org/uniprot/O60733)</div>
<div class="infobox-row"><strong>Associated Diseases</strong></div>
<div class="infobox-row">[Parkinson's Disease](/diseases/parkinsons-disease), [Infantile Neuroaxonal Dystrophy (INAD)](/diseases/infantile-neuroaxonal-dystrophy), [Phospholipase 2G6-Associated Neurodegeneration (PLAN)](/diseases/pla2g6-associated-neurodegeneration), [Ataxia with Oculomotor Apraxia](/diseases/ataxia-oculomotor-apraxia)</div>
</div>

Function

Phospholipase A2 Group VI (PLA2G6) encodes iPLA2-VIA, a calcium-independent phospholipase A2 enzyme that hydrolyzes the sn-2 position of phospholipids to release free fatty acids and lysophospholipids . This enzyme plays crucial roles in membrane remodeling, lipid signaling, and cellular homeostasis.

Key Functions

• Membrane Phospholipid Remodeling: Regulates phospholipid composition and turnover
• Lipid Mediator Synthesis: Produces arachidonic acid and other fatty acids for eicosanoid synthesis
• Mitochondrial Function: Maintains mitochondrial membrane integrity
• [Autophagy](/entities/autophagy): Regulates autophagosome formation and lipid metabolism
• Neuronal Survival: Protects against oxidative stress and mitochondrial dysfunction

Disease Associations

Parkinson's Disease

Rare heterozygous PLA2G6 mutations have been associated with late-onset Parkinson's disease, typically with atypical features . The role of PLA2G6 in sporadic PD remains under investigation.

Infantile Neuroaxonal Dystrophy (INAD)

Biallelic PLA2G6 mutations cause INAD, a progressive neurodegenerative disorder characterized by:

• Onset: Typically in first 2 years of life
• Clinical features: Developmental regression, hypotonia, spasticity, optic atrophy
• MRI findings: Diffuse cerebellar atrophy, iron deposition in globus pallidus
• Prognosis: Progressive, often fatal in childhood

Phospholipase 2G6-Associated Neurodegeneration (PLAN)

This umbrella term includes INAD and milder phenotypes with later onset:

• Ataxia with Oculomotor Apraxia (AOA4): Later onset, slower progression
• Adult-onset dystonia-parkinsonism: Rare presentation

Expression

PLA2G6 is widely expressed:

• Brain: High expression in cerebellum, basal ganglia, cerebral [cortex](/brain-regions/cortex)
• Neurons: Enriched in neurons and glia
• Peripheral tissues: Heart, liver, skeletal muscle
• Subcellular localization: Cytosolic and membrane-associated

Pathogenic Mechanisms

Therapeutic Implications

• Enzyme replacement: Not yet feasible due to size
• Lipid supplementation: May provide symptomatic benefit
• Antioxidant therapy: Targeting oxidative stress
• Gene therapy: AAV-mediated delivery being explored

Key Publications

See Also

• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Infantile Neuroaxonal Dystrophy](/diseases/infantile-neuroaxonal-dystrophy)
• [Phospholipase 2G6-Associated Neurodegeneration](/diseases/pla2g6-associated-neurodegeneration)
• [Neurodegeneration with Brain Iron Accumulation](/diseases/neurodegeneration-iron)
• [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction-ad)
• [Oxidative Stress](/mechanisms/oxidative-stress)

External Links

• [NCBI Gene: PLA2G6](https://www.ncbi.nlm.nih.gov/gene/503538)
• [UniProt: O60733](https://www.uniprot.org/uniprot/O60733)
• [Ensembl: ENSG00000156467](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000156467)
• [Allen Brain Atlas: PLA2G6](https://human.brain-map.org/microarray/search/show?search_term=PLA2G6)

Background

The study of Pla2G6 — Phospholipase A2 Group Vi has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

• [Allen Human Brain Atlas - PLA2G6 Expression](https://human.brain-map.org/microarray/search/show?search_term=PLA2G6)
• [Allen Cell Type Atlas - PLA2G6](https://celltypes.brain-map.org/)
• [BrainSpan - PLA2G6 Developmental Expression](https://brainspan.org/)
• [Allen Mouse Brain Atlas - PLA2G6](https://mouse.brain-map.org/)

References

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [Senescence-Associated Myelin Lipid Remodeling](/hypothesis/h-bb518928) — <span style="color:#ffd54f;font-weight:600">0.51</span> · Target: PLA2G6/PLA2G4A

Pathway Diagram

The following diagram shows the key molecular relationships involving PLA2G6 — Phospholipase A2 Group VI discovered through SciDEX knowledge graph analysis: