PFN1 Gene

PFN1 — Profilin 1

Introduction

Pfn1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@smith2015]
<table> [@aladesuyi2019]
<tr><th colspan="2" style="background:#6a1b9a;color:white;">PFN1 Gene</th></tr> [@tanaka2020]
<tr><td><b>Full Name</b></td><td>Profilin 1</td></tr> [@boopathy2021]
<tr><td><b>Chromosome</b></td><td>17p13.2</td></tr> [@deng2021]
<tr><td><b>NCBI Gene ID</b></td><td>[5297](https://www.ncbi.nlm.nih.gov/gene/5297)</td></tr> [@chesebro2022]
<tr><td><b>OMIM ID</b></td><td>[176580](https://www.omim.org/entry/176580)</td></tr> [@liu2023]
<tr><td><b>Ensembl ID</b></td><td>[ENSG00000108518](https://www.ensembl.org/Human/Gene/Summary?g=ENSG00000108518)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P07737](https://www.uniprot.org/uniprot/P07737)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia</td></tr>
</table>
</div>

Overview

PFN1 — Profilin 1

Introduction

Pfn1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@smith2015]
<table> [@aladesuyi2019]
<tr><th colspan="2" style="background:#6a1b9a;color:white;">PFN1 Gene</th></tr> [@tanaka2020]
<tr><td><b>Full Name</b></td><td>Profilin 1</td></tr> [@boopathy2021]
<tr><td><b>Chromosome</b></td><td>17p13.2</td></tr> [@deng2021]
<tr><td><b>NCBI Gene ID</b></td><td>[5297](https://www.ncbi.nlm.nih.gov/gene/5297)</td></tr> [@chesebro2022]
<tr><td><b>OMIM ID</b></td><td>[176580](https://www.omim.org/entry/176580)</td></tr> [@liu2023]
<tr><td><b>Ensembl ID</b></td><td>[ENSG00000108518](https://www.ensembl.org/Human/Gene/Summary?g=ENSG00000108518)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P07737](https://www.uniprot.org/uniprot/P07737)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia</td></tr>
</table>
</div>

Overview

Profilin 1 is a small actin-binding protein that regulates actin polymerization and is crucial for cytoskeletal dynamics. Mutations in PFN1 are associated with familial ALS and contribute to cytoskeletal dysfunction in motor [neurons](/entities/neurons).

Function

The PFN1 gene encodes profilin-1, a 140-amino acid actin-binding protein that regulates actin cytoskeleton dynamics. Profilin-1 binds to monomeric (G-actin) and filamentous (F-actin) forms, promoting actin polymerization and facilitating actin filament turnover.

Molecular Mechanism

Neuronal Functions

• Axon Guidance: Profilin-mediated actin dynamics essential for growth cone navigation
• Synaptic Plasticity: Actin cytoskeleton remodeling at [dendritic spines](/cell-types/dendritic-spines)
• Mitochondrial Transport: Actin-based motors for mitochondrial trafficking
• Autophagosome Formation: Profilin involved in autophagosome biogenesis

Expression Pattern

PFN1 is ubiquitously expressed but shows highest expression in:

• Motor neurons of the spinal cord
• Cortical pyramidal neurons
• Hippocampal CA1 pyramidal cells
• Cerebellar Purkinje cells

Disease Associations

PFN1 mutations are associated with the following neurodegenerative diseases:

| Disease | Inheritance | Key Mutations | Mechanism |
|---------|-------------|---------------|-----------|
| Amyotrophic Lateral Sclerosis (ALS) | Autosomal Dominant | Various | Protein aggregation, autophagy dysfunction |
| Frontotemporal Dementia (FTD) | Autosomal Dominant | Various | [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology, mitochondrial dysfunction |

Expression

PFN1 is expressed in various tissues including brain, with particular expression in neurons and glial cells. Expression data from the Allen Brain Atlas indicates regional specificity in the brain.

Key Publications

See Also

• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
• [Protein Quality Control Network](/mechanisms/protein-quality-control-network)
• [Autophagy-Lysosomal Pathway](/mechanisms/autophagy-lysosomal-pathway)
• [Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction-pathway)
• [TDP-43 Proteinopathy](/proteins/tdp-43)

External Links

• [NCBI Gene: PFN1](https://www.ncbi.nlm.nih.gov/gene/5297)
• [UniProt: PFN1](https://www.uniprot.org/uniprot/P07737)
• [Ensembl: PFN1](https://www.ensembl.org/Human/Gene/Summary?g=ENSG00000108518)
• [Allen Brain Atlas: PFN1](https://human.brain-map.org/microarray/search/show?search_term=PFN1)

Background

The study of Pfn1 Gene 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.

Molecular Mechanism

Profilin 1 is a 140-amino acid actin-binding protein that plays essential roles in actin cytoskeleton dynamics:

Actin Cycle Regulation

• Monomer binding: PFN1 binds G-actin (globular actin) with high affinity
• Nucleotide exchange: Facilitates ATP exchange on actin monomers
• Filament elongation: Promotes actin polymerization at barbed ends
• Thymosin β4 competition: Competes with thymosin β4 for G-actin binding

Protein Interactions

• Polyproline proteins: Binds via LIM domains
• Cofilin: Regulates cofilin-actin interactions
• Rho GTPases: Links signaling to cytoskeletal changes
• SMN complex: Involved in snRNP assembly

Neuronal Functions

• Axonal growth: Lamellipodia formation during development
• Synaptic plasticity: Actin remodeling at synapses
• Transport: Cytoskeletal tracks for vesicle trafficking
• mitochondrial distribution: Mitochondrial motility and positioning

Therapeutic Approaches

Targeting PFN1 dysfunction in ALS:

Small Molecule Strategies

• Actin-stabilizing compounds: Promote proper actin dynamics
• Modulators of actin polymerization: Restore cytoskeletal balance
• Neuroprotective agents: Address downstream effects

Gene Therapy

• AAV-PFN1: Wild-type PFN1 delivery
• Antisense oligonucleotides: Reduce toxic mutant expression
• CRISPR editing: Correct pathogenic mutations

Biomarker Potential

• ALS progression marker
• Therapeutic response indicator
• Disease stratification tool

Animal Models

Several PFN1 models have been developed:

• Transgenic mice: Wild-type and mutant PFN1 overexpression
• Knockin models: Human PFN1 mutations in mouse genome
• zebrafish models: Morpholino knockdown studies
• In vitro: Motor neuron cultures from patient iPSCs

References