DNM1 Gene

DNM1 - Dynamin 1

Introduction

Dnm1 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"> [@antonny2020]
<table> [@dhindsa2015]
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Dynamin 1</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>DNM1</td></tr>
<tr><td><strong>Full Name</strong></td><td>Dynamin 1</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>12p11.21</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[1756](https://www.ncbi.nlm.nih.gov/gene/1756)</td></tr>
<tr><td><strong>OMIM</strong></td><td>602377</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000106976</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q05193](https://www.uniprot.org/uniprot/Q05193)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Epilepsy, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Alzheimer's Disease</td></tr>
</table>
</div>

Overview

...

DNM1 - Dynamin 1

Introduction

Dnm1 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"> [@antonny2020]
<table> [@dhindsa2015]
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Dynamin 1</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>DNM1</td></tr>
<tr><td><strong>Full Name</strong></td><td>Dynamin 1</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>12p11.21</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[1756](https://www.ncbi.nlm.nih.gov/gene/1756)</td></tr>
<tr><td><strong>OMIM</strong></td><td>602377</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000106976</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q05193](https://www.uniprot.org/uniprot/Q05193)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Epilepsy, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Alzheimer's Disease</td></tr>
</table>
</div>

Overview

DNM1 encodes Dynamin 1, a large GTPase essential for synaptic vesicle endocytosis. Dynamin 1 is specifically expressed in [neurons](/entities/neurons) and plays a critical role in clathrin-mediated synaptic vesicle recycling, making it fundamental to maintaining synaptic function[@ferguson2012]. As a member of the dynamin family (DNM1, DNM2, DNM3), dynamin 1 mediates the final step of membrane fission during endocytosis, enabling synaptic vesicles to be recycled for subsequent rounds of neurotransmitter release[@antonny2020].

Gene Structure

• Chromosomal location: 12p11.21
• Genomic size: ~20 kb
• Exons: 22 exons
• Promoter: Neuron-specific expression elements

Protein Structure

Domain Organization

Dynamin 1 is a ~864 amino acid protein with distinct functional domains:

| Domain | Position | Function |
|--------|----------|----------|
| N-terminal GTPase | 1-300 | Catalyzes GTP hydrolysis |
| Middle domain | 300-500 | Protein-protein interactions |
| PH domain | 500-650 | Membrane binding |
| GTPase effector | 650-750 | Oligomer assembly |
| C-terminal proline-rich | 750-864 | Interactions with SH3 domains |

Molecular Mechanism

Vesicle scission: Polymerizes around vesicle neck

GTP hydrolysis: Conformational changes drive membrane fission

Regulation: Phosphorylation/dephosphorylation controls activity

Post-Translational Modifications

• Phosphorylation: Multiple serine/threonine sites
• Ubiquitination: Regulates protein stability
• SUMOylation: Alters subcellular localization

Molecular Function

Synaptic Vesicle Recycling

Dynamin 1 is essential for neuronal function:

Clathrin coat assembly: Initiates vesicle formation

Neck constriction: Polymerizes around vesicle neck

Membrane fission: GTP hydrolysis drives scission

Vesicle release: Coordinated with actin dynamics

GTPase Cycle

• GTP binding: Induces conformational change
• Oligomerization: Forms helical spirals
• GTP hydrolysis: Powers conformational constriction
• Product release: GDP-bound form dissociates

Protein Interactions

• Clathrin: Coat component
• Amphiphysin: BAR domain scaffold
• Endophilins: Curvature-inducing proteins
• Dynamitin: Regulates dynactin complex

Expression Pattern

Tissue Distribution

• Brain: Neuron-specific, very high expression
• Other tissues: Minimal expression

Brain Region Distribution

| Region | Expression Level | Cellular Localization |
|--------|-----------------|---------------------|
| [Hippocampus](/brain-regions/hippocampus) | Very High | All neuronal types |
| Cerebral [Cortex](/brain-regions/cortex) | Very High | Pyramidal cells, interneurons |
| Basal Ganglia | High | Medium spiny neurons |
| Cerebellum | High | Purkinje cells, granule cells |
| Brainstem | Moderate | Motor and sensory neurons |

Role in Disease

Epilepsy

DNM1 mutations cause early-onset epileptic encephalopathy:

• Inheritance: Autosomal dominant, de novo
• Phenotype: Infantile seizures, developmental delay
• Mechanism: Gain-of-function enhances vesicle dynamics
• Treatment: Anti-seizure medications, ketogenic diet[@dhindsa2015]

Alzheimer's Disease

• Pathology: Altered expression in AD brain
• Mechanism: Impaired synaptic vesicle recycling
• [Aβ](/proteins/amyloid-beta) interaction: Colocalization with plaques
• Therapeutic target: Modulators in development

Parkinson's Disease

• Risk variants: GWAS-identified DNM1 variants
• Dopaminergic neurons: Enhanced vulnerability
• Synaptic dysfunction: Contributes to degeneration

Huntington's Disease

• Mutant [HTT](/proteins/htt-protein): Interferes with DNM1 function
• Synaptic pathology: Impaired vesicle recycling
• Therapeutic implications: Restoration strategies

Therapeutic Approaches

Drug Development

• Dynamin inhibitors: Target membrane fission
• GTPase modulators: Modify activity
• Kinase inhibitors: Control phosphorylation

Gene Therapy

• AAV-mediated DNM1 delivery approaches
• Viral vector targeting strategies

Research Directions

Structural studies: High-resolution structures

Therapeutic development: Brain-penetrant inhibitors

Genetics: Variant pathogenicity

Biomarkers: Synaptic dysfunction markers

Animal models: Knockout and transgenic

Animal Models

• Dnm1 knockout: Fatal shortly after birth
• Conditional knockouts: Reveal essential neuronal role
• Transgenic: Disease-associated variants

See Also

• [Dynamin 1 Protein](/dynamin-1-protein)
• [DNM2 Gene](/proteins/dnm2-protein)
• [Dynamin 3](/proteins/dnm3-protein)
• [Clathrin-Mediated Endocytosis](/mechanisms/clathrin-endocytosis)
• [Synaptic Vesicle Recycling](/mechanisms/synaptic-vesicle-recycling)
• [Epilepsy](/diseases/epilepsy)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: DNM1](https://www.ncbi.nlm.nih.gov/gene/1756)
• [UniProt: Q05193](https://www.uniprot.org/uniprot/Q05193)
• [OMIM: 602377](https://www.omim.org/entry/602377)
• [Ensembl: ENSG00000106976](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000106976)
• [Allen Brain Atlas: DNM1](https://human.brain-map.org/microarray/search/show?search_term=DNM1)

Background

The study of Dnm1 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.

References

Ferguson SM, De Camilli P, Dynamin, a membrane-remodelling GTPase (2012)

Antonny B, et al, Membrane fission: a dynamic process (2020)

Dhindsa RS, et al, De novo DNM1 mutations cause early-onset epileptic encephalopathy (2015)