DPM1 Gene (Dolichol-Phosphate Mannosyltransferase Subunit 1)
Overview <table class="infobox infobox-gene">
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">
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-phosphateDPM Synthesis : Produces dolichol-phosphate mannose as the key intermediateGlycosylation Initiation : DPM is the essential donor for N-linked protein glycosylationBiological Significance The DPM complex is essential for:
Protein N-glycosylation : Over 50% of human proteins are glycosylatedER Quality Control : Glycosylation is crucial for proper protein foldingMembrane Protein Maturation : Many neuronal receptors require proper glycosylationRole 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 tauopathiesSynaptic 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 controlDopaminergic Vulnerability : Glycosylation defects may contribute to neuronal susceptibilityCongenital Disorders of Glycosylation DPM1 mutations cause Congenital Disorder of Glycosylation Type I (CDG), characterized by:
Severe Neurological Impairment : Developmental delay, intellectual disabilityAtaxia : Cerebellar involvement causing coordination problemsSeizures : Epileptic activity in affected individualsSystemic Features : Coagulopathy, dysmorphic features, immune dysfunctionExpression 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 cerebellumLiver : Hepatocytes with extensive ER contentMuscle : Skeletal and cardiac musclePancreas : Islet cellsTherapeutic Implications DPM1 is a potential therapeutic target:
CDG Treatment : Enzyme replacement or substrate supplementation approachesER Stress Modulators : Reducing UPR burden in glycosylation defectsChaperone Therapy : Small molecules to enhance DPM complex functionGenetic 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 mutationsNewborn Screening : Metabolic screening can detect some CDG typesPrognosis : Phenotype varies from mild to severe based on mutation typePathway & Interaction Diagram Interactive diagram showing DPM1's key relationships in the SciDEX knowledge graph (6 connections shown).
Mermaid diagram (expand to render)
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
Unknown, DPM1 catalytic subunit function (n.d.)
Unknown, Dolichol-phosphate mannose synthesis (n.d.)
Unknown, APP glycosylation in Alzheimer's disease (n.d.)
Unknown, Synaptic protein glycosylation (n.d.)
Unknown, Alpha-synuclein post-translational modifications (n.d.) Show full description