DYRK2

Chr 12

dual specificity tyrosine phosphorylation regulated kinase 2

NCBI Gene: 8445ENSG00000127334UniProt: Q92630

DYRK2 belongs to a family of protein kinases whose members are presumed to be involved in cellular growth and/or development. The family is defined by structural similarity of their kinase domains and their capability to autophosphorylate on tyrosine residues. DYRK2 has demonstrated tyrosine autophosphorylation and catalyzed phosphorylation of histones H3 and H2B in vitro. Two isoforms of DYRK2 have been isolated. The predominant isoform, isoform 1, lacks a 5' terminal insert. [provided by RefSeq, Jul 2008]

77
ClinVar variants
10
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DYRK2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 64 VUS of 77 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.17LOEUF
pLI 0.998
Z-score 3.88
OE 0.00 (0.00–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.95Z-score
OE missense 0.71 (0.64–0.78)
246 obs / 348.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.64–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 0 / 17.6Missense obs/exp: 246 / 348.6Syn Z: 0.36

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS64
Likely Benign2
Benign1
10
Pathogenic
64
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
63
1
0
64
Likely Benign
0
0
0
2
2
Benign
0
0
0
1
1
Total06311377

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DYRK2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The diverse functions of DYRK2 in response to cellular stress.
Kawamura A et al.·Histol Histopathol
2024Review
DYRK2 controls a key regulatory network in chronic myeloid leukemia stem cells.
Park CS et al.·Exp Mol Med
2020Review
DYRK2 downregulation in colorectal cancer leads to epithelial-mesenchymal transition induction and chemoresistance.
Wu C et al.·Sci Rep
2022
Curcuminoids WM03 inhibits ovarian cancer cisplatin-resistant cells proliferation and reverses cisplatin resistance by targeting DYRK2.
Zhang MJ et al.·Phytomedicine
2025
2-Aminobenzothiazoles in anticancer drug design and discovery.
Huang G et al.·Bioorg Chem
2023Review
A novel cardiomyopathy phenotype linked to a CHD7 missense variant.
Park IY et al.·Sci Rep
2025
Kinase DYRK2 acts as a regulator of autophagy and an indicator of favorable prognosis in gastric carcinoma.
Zhang X et al.·Colloids Surf B Biointerfaces
2022
Forced expression of DYRK2 exerts anti-tumor effects via apoptotic induction in liver cancer.
Yokoyama-Mashima S et al.·Cancer Lett
2019
DYRK2 regulates epithelial-mesenchymal-transition and chemosensitivity through Snail degradation in ovarian serous adenocarcinoma.
Yamaguchi N et al.·Tumour Biol
2015
Preclinical Efficacy of TSL2109 in Prostate Cancer Treatment and Overcoming Enzalutamide Resistance.
Yuan K et al.·J Med Chem
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A physics-informed graph neural network to approximate docking-based binding affinity for DYRK2 in Alzheimer's drug repurposing.
Gider V et al.·Sci Rep
2026🔓 Open Access
The dual fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis.
Suanes-Cobos L et al.·Cancer Metastasis Rev
2026🔓 Open Access
A novel feedback loop between DYRK2 and USP28 regulates cancer homeostasis and DNA damage signaling.
Suanes-Cobos L et al.·Cell Death Differ
2026🔓 Open Access
Benzamide Derivatives of Thioacridine as DYRK2 and DYRK3 Dual Inhibitors.
Roussel J et al.·ChemMedChem
2025
Identification of DYRK2 and TRIM32 as keloids programmed cell death-related biomarkers: insights from bioinformatics and machine learning in multiple cohorts.
Yang X et al.·Comput Methods Biomech Biomed Engin
2025Cohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools