DYRK1A Gene - Dual Specificity Tyrosine-Phosphorylation Regulated Kinase 1A

DYRK1A Gene

Introduction

Dyrk1A Gene Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about DYRK1A Gene, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases.

DYRK1A Gene

Introduction

Dyrk1A Gene Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about DYRK1A Gene, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases.

<div class="infobox infobox-gene">
<div class="infobox-header">DYRK1A</div>
<div class="infobox-content">
<table>
<tr><td><strong>Full Name</strong></td><td>Dual Specificity Tyrosine-Phosphorylation Regulated Kinase 1A</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>21q22.13</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td><a href="https://www.ncbi.nlm.nih.gov/gene/1785" target="_blank">1785</a></td></tr>
<tr><td><strong>OMIM</strong></td><td><a href="https://www.omim.org/entry/600855" target="_blank">600855</a></td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000157540</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/Q13627" target="_blank">Q13627</a></td></tr>
<tr><td><strong>Protein</strong></td><td>DYRK1A (Minibrain)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Down Syndrome, [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Autism, Intellectual Disability</td></tr>
</table>
</div>
</div>

Function

The DYRK1A gene encodes Dual Specificity Tyrosine-Phosphorylation Regulated Kinase 1A, a member of the dual-specificity tyrosine-regulated kinase (DYRK) family. DYRK1A is located in the Down syndrome critical region (DSCR) of chromosome 21 and is overexpressed in individuals with trisomy 21 (Down syndrome). The kinase is a serine/threonine kinase that autophosphorylates on a tyrosine residue within its activation loop and subsequently phosphorylates numerous substrate proteins on serine/threonine residues.

DYRK1A is expressed throughout the brain during development and adulthood, with particularly high expression in regions important for learning and memory, including the hippocampus and cerebral cortex.

Key Functions:

• Protein Phosphorylation: Phosphorylates numerous substrates involved in transcription, splicing, translation, and cytoskeletal dynamics
• Synaptic Plasticity: Regulates synaptic protein synthesis and spine morphology
• Cell Cycle Control: Modulates cell cycle progression through phosphorylation of cyclins and CDKs
• Neurodevelopment: Critical for proper brain development and neuronal differentiation
• Learning and Memory: Regulates proteins involved in learning and memory consolidation

Disease Associations

Alzheimer's Disease

• DYRK1A is overexpressed in AD brains (due to trisomy 21 in many AD patients with DS)
• Phosphorylates [tau](/proteins/tau) protein at multiple sites (Thr181, Ser202, Thr205, Thr217, Thr231)
• Promotes [amyloid-beta](/proteins/amyloid-beta) production through [APP](/entities/app-protein) processing
• Contributes to synaptic dysfunction and cognitive decline
• DYRK1A inhibitors (e.g., harmine, leucettine L41) show promise in preclinical AD models

Parkinson's Disease

• DYRK1A phosphorylates [alpha-synuclein](/proteins/alpha-synuclein) at Ser129 (a key modification in Lewy body formation)
• Regulates [LRRK2](/entities/lrrk2) kinase activity
• Involved in dopaminergic neuron function
• Elevated activity may contribute to [alpha-synuclein](/proteins/alpha-synuclein) pathology

Down Syndrome (Trisomy 21)

• Gene triplication causes overexpression (1.5x dosage)
• Contributes to intellectual disability characteristic of DS
• Associated with early-onset Alzheimer-like pathology
• Mouse models (Ts65Dn) show DYRK1A involvement in learning deficits

Autism Spectrum Disorder

• De novo mutations in DYRK1A cause autosomal dominant mental retardation type 7
• Associated with autism spectrum disorders
• Affects synaptic function and social behavior

Expression

DYRK1A is expressed in:

• [Hippocampus](/brain-regions/hippocampus): High expression in CA1-CA3 pyramidal [neurons](/entities/neurons) and dentate gyrus
• [Cortex](/brain-regions/cortex): All cortical layers, particularly pyramidal neurons
• Cerebellum: Purkinje cells and granule cells
• Substantia Nigra: Dopaminergic neurons
• Thalamus: Various nuclei

• Highest during fetal brain development
• Maintained at lower levels in adult brain
• Cell type-specific (neurons > glia)
• Activity-dependent regulation

Key Publications

Therapeutic Targeting

| Approach | Description | Status |
|----------|-------------|--------|
| DYRK1A Inhibitors | Harmine, leucettine L41, INDY | Preclinical/clinical trials |
| Natural Compounds | EGCG (green tea) inhibits DYRK1A | Clinical trials |
| Gene Therapy | siRNA to reduce overexpression | Research |

Background

The study of Dyrk1A Gene Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A 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.

Brain Atlas Resources

Allen Brain Atlas Links

The Allen Brain Atlas provides comprehensive gene expression data across brain regions and cell types.

• [Allen Human Brain Atlas](https://human.brain-map.org/) — Gene expression data across the adult human brain
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — Gene expression in mouse brain
• [Allen Cell Type Atlas](https://celltype.brain-map.org/) — Single-cell transcriptomics data
• [BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/) — Developmental expression data
• [Allen Brain Map Portal](https://portal.brain-map.org/) — Access to all Allen Institute brain data

Gene-Specific Expression Data

Search for expression data on the Allen Brain Atlas:

• [Human Brain Atlas search for this gene](https://human.brain-map.org/microarray/search/show?search_term=DYRK1A)

References

^{[[1]](https://pubmed.ncbi.nlm.nih.gov/20102701/)} DYRK1A and Alzheimer disease. PMID: 20102701(https://pubmed.ncbi.nlm.nih.gov/20102701/)

See Also

• [Tau Pathology Pathway](/mechanisms/tau-pathology)
• [Alpha-Synuclein Aggregation Pathway](/mechanisms/alpha-synuclein-pathology)
• APP Gene
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• Down Syndrome and Neurodegeneration

External Links

• [NCBI Gene: DYRK1A](https://www.ncbi.nlm.nih.gov/gene/1785)
• [UniProt: DYRK1A](https://www.uniprot.org/uniprot/Q13627)
• [OMIM: DYRK1A](https://www.omim.org/entry/600855)
• [GeneCards: DYRK1A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=DYRK1A)

Pathway Diagram

The following diagram shows the key molecular relationships involving DYRK1A Gene - Dual Specificity Tyrosine-Phosphorylation Regulated Kinase 1A discovered through SciDEX knowledge graph analysis: