DPM1 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 1)

DPM1 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 1)

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DPM1 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 1)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>DPM1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DPM1 (Dolichol-Phosphate Mannosyltransferase Subunit 1)</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=DPM1" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/congenital-disorders-of-glycosylation" style="color:#ef9a9a">Congenital Disorders of Glycosylation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>

Gene Symbol: DPM1 Full Name: Dolichol-Phosphate Mannosyltransferase Subunit 1 Chromosomal Location: 20q13.13 NCBI Gene ID: [8813](https://www.ncbi.nlm.nih.gov/gene/8813) OMIM: [603503](https://www.omim.org/entry/603503) Ensembl ID: ENSG00000024219 UniProt: [O60711](https://www.uniprot.org/uniprot/O60711)

Function

DPM1 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 1)

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DPM1 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 1)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>DPM1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DPM1 (Dolichol-Phosphate Mannosyltransferase Subunit 1)</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=DPM1" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/congenital-disorders-of-glycosylation" style="color:#ef9a9a">Congenital Disorders of Glycosylation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>

Gene Symbol: DPM1 Full Name: Dolichol-Phosphate Mannosyltransferase Subunit 1 Chromosomal Location: 20q13.13 NCBI Gene ID: [8813](https://www.ncbi.nlm.nih.gov/gene/8813) OMIM: [603503](https://www.omim.org/entry/603503) Ensembl ID: ENSG00000024219 UniProt: [O60711](https://www.uniprot.org/uniprot/O60711)

Function

The DPM1 gene encodes the catalytic subunit of the dolichol-phosphate mannose (DPM) synthase complex [@dpm]. DPM1 is the enzymatically active component of the complex, which also includes DPM2 (regulatory subunit) and DPM3 (scaffold subunit). This complex catalyzes the synthesis of dolichol-phosphate mannose (DPM), a critical donor substrate for protein glycosylation in the endoplasmic reticulum [@dolicholphosphate].

Catalytic Activity

DPM1 possesses the enzymatic activity responsible for:

• Mannose Transfer: Catalyzes the transfer of mannose from GDP-mannose to dolichol-phosphate
• DPM Synthesis: Produces dolichol-phosphate mannose as the key intermediate
• Glycosylation Initiation: DPM is the essential donor for N-linked protein glycosylation

Biological Significance

The DPM complex is essential for:

• Protein N-glycosylation: Over 50% of human proteins are glycosylated
• ER Quality Control: Glycosylation is crucial for proper protein folding
• Membrane Protein Maturation: Many neuronal receptors require proper glycosylation

Role in Neurodegenerative Diseases

Alzheimer's Disease

DPM1 dysfunction may contribute to Alzheimer's disease through multiple mechanisms:

• Amyloid Processing: Proper glycosylation affects [amyloid precursor protein](/entities/app-protein) (APP) processing and [amyloid-beta](/proteins/amyloid-beta) generation [@app]
• [Tau](/proteins/tau) Glycosylation: Abnormal glycosylation patterns have been documented in tauopathies
• Synaptic Dysfunction: Glycosylation of synaptic receptors and adhesion molecules is essential for synaptic plasticity [@synaptic]
• ER Stress: Impaired glycosylation triggers [unfolded protein response](/entities/unfolded-protein-response) (UPR)

Parkinson's Disease

• [Alpha-Synuclein](/proteins/alpha-synuclein): Glycosylation patterns influence alpha-synuclein aggregation and toxicity [@alphasynuclein]
• Protein Homeostasis: Disrupted glycosylation affects cellular protein quality control
• Dopaminergic Vulnerability: Glycosylation defects may contribute to neuronal susceptibility

Congenital Disorders of Glycosylation

DPM1 mutations cause Congenital Disorder of Glycosylation Type I (CDG), characterized by:

• Severe Neurological Impairment: Developmental delay, intellectual disability
• Ataxia: Cerebellar involvement causing coordination problems
• Seizures: Epileptic activity in affected individuals
• Systemic Features: Coagulopathy, dysmorphic features, immune dysfunction

Expression Patterns

DPM1 is ubiquitously expressed with high levels in:

• Brain: [Neurons](/entities/neurons) throughout the cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and cerebellum
• Liver: Hepatocytes with extensive ER content
• Muscle: Skeletal and cardiac muscle
• Pancreas: Islet cells

Therapeutic Implications

DPM1 is a potential therapeutic target:

• CDG Treatment: Enzyme replacement or substrate supplementation approaches
• ER Stress Modulators: Reducing UPR burden in glycosylation defects
• Chaperone Therapy: Small molecules to enhance DPM complex function

Genetic Associations

• DPM1 mutations cause autosomal recessive CDG-Ia (the most common CDG type)
• Compound heterozygous mutations often cause milder phenotypes
• Carrier testing is available for at-risk families

Clinical Significance

DPM1 dysfunction is clinically relevant for:

• Diagnosis: Genetic testing for DPM1 mutations
• Newborn Screening: Metabolic screening can detect some CDG types
• Prognosis: Phenotype varies from mild to severe based on mutation type

Pathway & Interaction Diagram

Interactive diagram showing DPM1's key relationships in the SciDEX knowledge graph (6 connections shown).

See Also

• [DPM2](/genes/dpm2) - Dolichol phosphate mannose biosynthesis subunit 2
• [DPM3](/genes/dpm3) - Dolichol phosphate mannose biosynthesis subunit 3
• [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) - DPM1-related metabolic disorder

External Links

• [NCBI Gene: DPM1](https://www.ncbi.nlm.nih.gov/gene/8813)
• [Ensembl: ENSG00000024219](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000024219)
• [UniProt: O60711](https://www.uniprot.org/uniprot/O60711)

References