DYRK1A: Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A
A key regulator of neurodevelopment, cell proliferation, and Down syndrome pathophysiology.
Gene Information Card
| Symbol | DYRK1A |
|---|---|
| Full Name | Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.13 |
| NCBI Gene ID | 1859 ncbi.nlm.nih.gov/gene/1859 |
| Ensembl ID | ENSG00000157540 |
| UniProt ID | Q13627 |
| OMIM ID | 600855 |
| HGNC ID | 3091 |
| Aliases | DYRK, DYRK1, HP86, MNB, MNBH, DYRK1A1 |
Description
DYRK1A encodes a dual-specificity kinase that phosphorylates serine, threonine, and tyrosine residues. It is a key regulator of cell proliferation, neurogenesis, and synaptic plasticity. Overexpression due to trisomy 21 contributes to Down syndrome phenotypes, while loss-of-function mutations cause DYRK1A-related intellectual disability syndrome (MRD7). DYRK1A also plays roles in cancer, Alzheimer disease, and diabetes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Down syndrome | Overexpression (gene dosage effect) leads to altered neurodevelopment, cognitive impairment, and increased risk of Alzheimer disease. | OMIM #190685; PMID: 27545674 |
| DYRK1A-related intellectual disability syndrome (MRD7) | Heterozygous loss-of-function mutations (nonsense, frameshift, missense) cause microcephaly, intellectual disability, autism, and seizures. | OMIM #614104; PMID: 26166481 |
| Alzheimer disease | DYRK1A phosphorylates tau and APP, promoting amyloid-beta production and tau pathology. | PMID: 22751012 |
| Acute myeloid leukemia (AML) | DYRK1A overexpression in AML cells promotes proliferation; inhibition induces differentiation. | PMID: 23327922 |
| Pancreatic cancer | DYRK1A overexpression correlates with poor prognosis; regulates cell cycle and apoptosis. | PMID: 29065170 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Testis | 8.2 | Medium |
| Heart | 6.1 | Medium |
| Liver | 3.4 | Low |
| Kidney | 4.8 | Medium |
| Pancreas | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used for neurodevelopmental studies |
| HEK293 (embryonic kidney) | 9.7 | Moderate expression; common overexpression model |
| K562 (leukemia) | 7.2 | Moderate expression; relevant for AML studies |
| HepG2 (hepatocellular carcinoma) | 4.5 | Low expression |
| MCF7 (breast cancer) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37*) | Nonsense | Rare | Loss of function; associated with MRD7 |
| c.632delC (p.Pro211Leufs*2) | Frameshift | Rare | Loss of function; associated with MRD7 |
| c.755G>A (p.Arg252His) | Missense | Rare | Loss of function; impaired kinase activity; MRD7 |
| c.1024A>G (p.Thr342Ala) | Missense | Rare | Loss of function; reduced autophosphorylation; MRD7 |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein production; MRD7 |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that reduce or abolish kinase activity or protein stability cause DYRK1A haploinsufficiency, leading to MRD7 (microcephaly, intellectual disability, autism).
Gain of Function (GOF)
Not well documented; overexpression in Down syndrome is due to gene dosage, not activating mutations. No recurrent gain-of-function mutations reported in COSMIC or ClinVar.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for DYRK1A. All reported pathogenic variants are loss-of-function with haploinsufficiency mechanism.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DYRK1A phosphorylates tau (MAPT) – Alzheimer disease pathway
• DYRK1A regulates NFAT signaling – cell proliferation and differentiation
• DYRK1A modulates NOTCH signaling – neurogenesis
• DYRK1A interacts with REST – neuronal gene silencing
• DYRK1A phosphorylates cyclin D1 (CCND1) – cell cycle control
Protein Summary
DYRK1A is a 763-amino-acid dual-specificity kinase with a conserved kinase domain and a nuclear localization signal. It autophosphorylates on tyrosine residues for activation and subsequently phosphorylates serine/threonine substrates. The protein is predominantly nuclear and regulates transcription factors (e.g., NFAT, CREB, STAT3), cell cycle proteins (e.g., cyclin D1, p27), and synaptic proteins (e.g., PSD-95). DYRK1A is essential for brain development, and its dysregulation is central to Down syndrome and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DYRK1A Knockout HEK293 Cell Line | EDJ-KQ4490 | Human | 1859 | Details Get a Quote |
| DYRK1A Knockout HeLa Cell Line | EDJ-KQ17942 | Human | 1859 | Details Get a Quote |
| DYRK1A Knockout A-549 Cell Line | EDJ-KQ27065 | Human | 1859 | Details Get a Quote |
| DYRK1A Knockout HCT 116 Cell Line | EDJ-KQ27066 | Human | 1859 | Details Get a Quote |
