DPM3 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 3)

DPM3 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 3)

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DPM3 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 3)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>DPM3</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DPM3 (Dolichol-Phosphate Mannosyltransferase Subunit 3)</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=DPM3" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">4 edges</a></td>
</tr>
</table>

Gene Symbol: DPM3 Full Name: Dolichol-Phosphate Mannosyltransferase Subunit 3 Chromosomal Location: 1q22 NCBI Gene ID: [54344](https://www.ncbi.nlm.nih.gov/gene/54344) OMIM: [605066](https://www.omim.org/entry/605066) Ensembl ID: ENSG00000133030 UniProt: [Q9BXS5](https://www.uniprot.org/uniprot/Q9BXS5)

Function

DPM3 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 3)

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DPM3 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 3)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>DPM3</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DPM3 (Dolichol-Phosphate Mannosyltransferase Subunit 3)</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=DPM3" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">4 edges</a></td>
</tr>
</table>

Gene Symbol: DPM3 Full Name: Dolichol-Phosphate Mannosyltransferase Subunit 3 Chromosomal Location: 1q22 NCBI Gene ID: [54344](https://www.ncbi.nlm.nih.gov/gene/54344) OMIM: [605066](https://www.omim.org/entry/605066) Ensembl ID: ENSG00000133030 UniProt: [Q9BXS5](https://www.uniprot.org/uniprot/Q9BXS5)

Function

The DPM3 gene encodes the third subunit of the dolichol-phosphate mannose (DPM) synthase complex, which is essential for protein N-glycosylation and glycolipid biosynthesis [@dolicholphosphate]. DPM3 plays a crucial role in maintaining the proper function of the DPM complex, which consists of DPM1 (catalytic subunit), DPM2 (regulatory subunit), and DPM3 (scaffold subunit) [@dpm].

Dolichol-Phosphate Mannose Synthesis

The DPM synthase complex catalyzes the synthesis of dolichol-phosphate mannose (DPM), a critical donor substrate for:

• N-linked Protein Glycosylation: Transfer of mannose to nascent polypeptides in the endoplasmic reticulum
• Glycolipid Biosynthesis: Synthesis of glycosylphosphatidylinositol (GPI) anchors
• C-mannosylation: Rare type of protein glycosylation

Neurological Function

Proper glycosylation is essential for neuronal function:

• Synaptic Proteins: Many synaptic receptors and adhesion molecules require proper glycosylation
• Ion Channel Function: Glycosylation affects ion channel trafficking and function
• Neuronal Development: Glycosylation patterns influence neuronal migration and connectivity

Role in Neurodegenerative Diseases

Alzheimer's Disease

DPM3 and the glycosylation pathway have been implicated in Alzheimer's disease:

• APP Processing: Glycosylation affects [amyloid precursor protein](/entities/app-protein) (APP) processing and [amyloid-beta](/proteins/amyloid-beta) production [@glycosylation]
• [Tau](/proteins/tau) Glycosylation: Abnormal glycosylation patterns have been observed in tauopathies
• Synaptic Glycoproteins: Disrupted glycosylation of synaptic proteins may contribute to synaptic loss
• ER Stress: Impaired glycosylation can trigger [unfolded protein response](/entities/unfolded-protein-response) (UPR)

Parkinson's Disease

• [Alpha-Synuclein](/proteins/alpha-synuclein) Glycosylation: Glycosylation patterns may affect alpha-synuclein aggregation and toxicity [@alphasynuclein]
• Dopaminergic Neuron Vulnerability: Glycosylation defects may contribute to dopaminergic neuron susceptibility
• ER Homeostasis: Disrupted protein quality control mechanisms

Congenital Disorders of Glycosylation

DPM3 mutations cause Congenital Disorder of Glycosylation Type Ie (CDG-Ie), characterized by:

• Neurological Impairment: Developmental delay, intellectual disability, ataxia
• Seizures: Epileptic episodes in affected individuals
• Muscular Issues: Hypotonia, muscular dystrophy-like features
• Cardiomyopathy: Some patients develop cardiac complications

Expression Patterns

DPM3 is ubiquitously expressed with highest levels in:

• Brain: Particularly in [neurons](/entities/neurons) of the cerebral [cortex](/brain-regions/cortex) and [hippocampus](/brain-regions/hippocampus)
• Muscle: Skeletal muscle and cardiac tissue
• Liver: High expression in hepatocytes
• ER-rich cells: Cells with extensive endoplasmic reticulum

Therapeutic Implications

Targeting the glycosylation pathway may have therapeutic potential:

• Chaperone Therapy: Small molecules that enhance DPM complex function
• Gene Therapy: AAV-mediated DPM3 delivery for CDG patients
• ER Stress Modulators: Reducing UPR burden in glycosylation defects

Genetic Associations

• DPM3 mutations cause autosomal recessive CDG-Ie
• Polymorphisms may affect glycosylation efficiency
• Gene-dosage effects in neurodegenerative disease

Clinical Significance

DPM3 dysfunction has clinical relevance for:

• CDG Diagnosis: Genetic testing for DPM3 mutations
• Therapeutic Monitoring: Assessing glycosylation efficiency
• Biomarker Development: Glycosylation patterns as disease markers

See Also

• [DPM1](/genes/dpm1) - Dolichol phosphate mannose biosynthesis subunit 1
• [DPM2](/genes/dpm2) - Dolichol phosphate mannose biosynthesis subunit 2
• [Alzheimer's Disease](/diseases/alzheimers-disease) - Related to glycosylation defects
• [Parkinson's Disease](/diseases/parkinsons-disease) - Protein glycosylation in neurodegeneration
• [Congenital Disorders of Glycosylation](/diseases/congenital-disorders-of-glycosylation) - DPM-related metabolic disorder

External Links

• [NCBI Gene: DPM3](https://www.ncbi.nlm.nih.gov/gene/54344)
• [Ensembl: ENSG00000133030](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000133030)
• [UniProt: Q9BXS5](https://www.uniprot.org/uniprot/Q9BXS5)

References