DYRK1A - a gene dose paradox.
6 affiliations
- 1Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia.
- 2Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 3Department of Pathophysiology, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia.
- 4Varaždin General Hospital, Varaždin, Croatia.
- 5ARUK-UCL Drug Discovery Institute, Faculty of Brain Sciences, University College London, London, United Kingdom.
- 6Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United Kingdom.
Abstract
The DYRK1A (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) gene is located on human chromosome 21 (HSA21) within the Down Syndrome Critical Region (DSCR). As a protein kinase, DYRK1A is involved in the regulation of the cell cycle, cell growth, transcription, and cellular communication. It also plays essential roles in embryonic and neuronal development, and in disease pathogenesis. Dysregulation of DYRK1A has been associated with several human disorders, including DYRK1A syndrome, caused by DYRK1A haploinsufficiency (i.e., one functional copy of the gene) and Down syndrome (DS), caused by trisomy 21 (i.e., three functional copies of the gene). DYRK1A is an extremely dosage-sensitive gene and is considered one of the "Goldilocks" genes, for which both increased and decreased gene dosage can lead to pathological phenotypes. Interestingly, these two syndromes share several overlapping clinical features. This apparent paradox represents/highlights a major gap in our current understanding of DYRK1A function and raises important biological questions. In this review, we summarise the most important findings related to both DYRK1A syndrome and Down syndrome, as well as the available human cellular and animal models that provide valuable platforms for future research. To obtain a comprehensive understanding of DYRK1A role, it is necessary to integrate data from multiple experimental systems and sources. Such an integrated approach will facilitate the identification of novel therapeutic targets and support the development of treatments that may ultimately advance to clinical trials.
Related
- APOE ε4 gene dose drives a canonical and predictable topography of amyloid deposition.
- Early dose stratification 4 h after ionizing radiation exposure using a peripheral blood transcriptional gene panel
- Chicoric acid-rich extract of Cichorium intybus seeds (CAREOCI) preserves pancreatic β-cell function under glucotoxic stress through modulation of MAFA, DYRK1A, cell cycle, apoptosis, and mitochondrial dysfunction
- Productivity Paradox of the AI-Augmented Inbox
- The LAI–Oral Antipsychotic Efficacy–Effectiveness Paradox in Schizophrenia
BibTeX
@article{plecas2026dyrk1a,
title = {{DYRK1A - a gene dose paradox.}},
author = {Ante Plećaš and Gillian Gough and Sandra Kunštek and Mirna Babić and Aoife Murray and Dean Nižetić and Ivan Alić},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1963992},
url = {https://europepmc.org/article/MED/42909264},
note = {CC BY},
}
RIS
TY - JOUR
TI - DYRK1A - a gene dose paradox.
AU - Ante Plećaš
AU - Gillian Gough
AU - Sandra Kunštek
AU - Mirna Babić
AU - Aoife Murray
AU - Dean Nižetić
AU - Ivan Alić
PY - 2026
DA - 2026/10/07
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1963992
UR - https://europepmc.org/article/MED/42909264
AB - The DYRK1A (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) gene is located on human chromosome 21 (HSA21) within the Down Syndrome Critical Region (DSCR). As a protein kinase, DYRK1A is involved in the regulation of the cell cycle, cell growth, transcription, and cellular communication. It also plays essential roles in embryonic and neuronal development, and in disease pathogenesis. Dysregulation of DYRK1A has been associated with several human disorders, including DYRK1A syndrome, caused by DYRK1A haploinsufficiency (i.e., one functional copy of the gene) and Down syndrome (DS), caused by trisomy 21 (i.e., three functional copies of the gene). DYRK1A is an extremely dosage-sensitive gene and is considered one of the "Goldilocks" genes, for which both increased and decreased gene dosage can lead to pathological phenotypes. Interestingly, these two syndromes share several overlapping clinical features. This apparent paradox represents/highlights a major gap in our current understanding of DYRK1A function and raises important biological questions. In this review, we summarise the most important findings related to both DYRK1A syndrome and Down syndrome, as well as the available human cellular and animal models that provide valuable platforms for future research. To obtain a comprehensive understanding of DYRK1A role, it is necessary to integrate data from multiple experimental systems and sources. Such an integrated approach will facilitate the identification of novel therapeutic targets and support the development of treatments that may ultimately advance to clinical trials.
SN - 2296-634X
ER -