DYRK1A
Chr 21ADdual specificity tyrosine phosphorylation regulated kinase 1A
Also known as: DYRK, DYRK1, HP86, MNB, MNBH, MRD7
This gene encodes a dual-specificity kinase that catalyzes autophosphorylation on serine/threonine and tyrosine residues and regulates cell proliferation and brain development. Mutations cause intellectual developmental disorder, autosomal dominant 7, predominantly through loss-of-function mechanisms. The gene shows extremely high constraint against loss-of-function variants (pLI 1.0, LOEUF 0.21), consistent with haploinsufficiency as the primary pathogenic mechanism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 13 | 0 | 1 | 0 | 14 |
Likely Pathogenic | 5 | 2 | 0 | 0 | 7 |
VUS | 0 | 19 | 2 | 1 | 22 |
Likely Benign | 0 | 4 | 14 | 33 | 51 |
Benign | 0 | 1 | 0 | 1 | 2 |
Conflicting | — | 4 | |||
| Total | 18 | 26 | 17 | 35 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DYRK1A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools