DYRK2

Summary

DYRK2 (dual specificity tyrosine phosphorylation regulated kinase 2, HGNC:3093) is a protein-coding gene on chromosome 12q15, encoding Dual specificity tyrosine-phosphorylation-regulated kinase 2 (Q92630). Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth.

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.

Source: NCBI Gene 8445 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 68 total
• Druggable target: yes — 30 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006482

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3093
Approved symbol	DYRK2
Name	dual specificity tyrosine phosphorylation regulated kinase 2
Location	12q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127334
Ensembl biotype	protein_coding
OMIM	603496
Entrez	8445

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000319833, ENST00000344096, ENST00000393555, ENST00000537632, ENST00000542503, ENST00000543747, ENST00000908892, ENST00000908893, ENST00000908894, ENST00000908895, ENST00000917019

RefSeq mRNA: 2 — MANE Select: NM_006482 NM_003583, NM_006482

CCDS: CCDS8978, CCDS8979

Canonical transcript exons

ENST00000344096 — 3 exons

Exon	Start	End
ENSE00001730364	67657106	67665406
ENSE00002238390	67648745	67649182
ENSE00003521323	67649797	67649945

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 93.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6228 / max 260.2484, expressed in 1789 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126572	20.4817	1783
126571	1.0266	663
126573	0.1145	25

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	93.88	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.31	gold quality
jejunum	UBERON:0002115	93.07	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.95	gold quality
colonic mucosa	UBERON:0000317	92.77	gold quality
cortical plate	UBERON:0005343	92.44	gold quality
vastus lateralis	UBERON:0001379	92.30	gold quality
quadriceps femoris	UBERON:0001377	91.61	gold quality
pylorus	UBERON:0001166	90.70	gold quality
biceps brachii	UBERON:0001507	90.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.16	gold quality
skeletal muscle tissue	UBERON:0001134	89.87	gold quality
visceral pleura	UBERON:0002401	89.70	gold quality
heart right ventricle	UBERON:0002080	88.95	gold quality
hair follicle	UBERON:0002073	88.89	gold quality
rectum	UBERON:0001052	88.82	gold quality
parietal pleura	UBERON:0002400	88.64	gold quality
saphenous vein	UBERON:0007318	88.63	gold quality
epithelium of nasopharynx	UBERON:0001951	88.44	gold quality
pleura	UBERON:0000977	88.39	gold quality
superficial temporal artery	UBERON:0001614	88.34	gold quality
muscle tissue	UBERON:0002385	88.33	gold quality
palpebral conjunctiva	UBERON:0001812	88.07	gold quality
duodenum	UBERON:0002114	87.88	gold quality
tibia	UBERON:0000979	87.32	gold quality
granulocyte	CL:0000094	87.17	gold quality
right atrium auricular region	UBERON:0006631	87.14	gold quality
cardiac atrium	UBERON:0002081	87.10	gold quality
thymus	UBERON:0002370	87.01	gold quality
deltoid	UBERON:0001476	86.59	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	585.97
E-ANND-3	yes	3.65
E-GEOD-124858	no	197.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

264 targeting DYRK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 34)

• These findings indicate that DYRK2 regulates p53 to induce apoptosis in response to DNA damage. (PMID:17349958)
• A protein kinase, DYRK2, has unexpected role as a scaffold for an E3 ubiquitin ligase complex. (PMID:19287380)
• disease control rate of the DYRK2-positive non-small cell lung cancer patients was significantly different from the DYRK2-negative group (PMID:19596956)
• The data showed that DYRK2 expression is associated with a favorable prognosis in pulmonary adenocarcinoma. (PMID:19818968)
• The findings indicate that ATM controls stability and pro-apoptotic function of DYRK2 in response to DNA damage. (PMID:19965871)
• DYRK2 regulates tumor progression through modulation of c-Jun and c-Myc (PMID:22307329)
• DYRK2-mediated phosphorylation of p53 at Ser46 is impaired under hypoxic conditions, suggesting a molecular mechanism underlying chemotherapy resistance in solid tumors. (PMID:22878263)
• Data indicate that Dyrk2 phosphorylates TERT protein, which is then associated with the EDD-DDB1-VprBP E3 ligase complex for subsequent ubiquitin-mediated TERT protein degradation. (PMID:23362280)
• DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail. (PMID:23791882)
• DYRK2-dependent phosphorylation of pregnane X receptor facilitates its subsequent ubiquitination by UBR5. (PMID:24438055)
• Downregulation of DYRK2 is associated with recurrence in early stage breast cancer. (PMID:25095982)
• DYRK2 may regulate EMT through Snail degradation in ovarian SA and might be a predictive marker for a favorable prognosis in the treatment of this cancer. (PMID:25712377)
• Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin’s Lymphoma (PMID:26341817)
• the downregulated expression of DYRK2 in HCC tumor tissues could promote the proliferation of hepatocellular carcinoma (HCC) cells. In addition, reducing DYRK2 expression was associated with poor prognosis and Oxaliplatin resistance in HCC. (PMID:26804244)
• lower DYRK2 levels were correlated with tumor sites, advanced clinical stages, and shorter survival in the advanced clinical stages. DYRK2 is a novel prognostic biomarker of human colorectal cancer. (PMID:27532268)
• our results delineate a novel mechanism of cancer stem cell regulation by the DYRK2-AR-KLF4 axis. Restoration of the expression and function of DYRK2 is a potential therapeutic strategy against breast cancer stem cells. (PMID:27721402)
• Diminished DYRK2 expression sensitizes hormone receptor-positive breast cancer to everolimus by preventing mTOR degradation. (PMID:27746162)
• Findings indicate direct interaction of dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) with ring finger protein (C3HC4 type) 8 (RNF8) in regulating response to DNA damage. (PMID:28194753)
• Study found that DYRK2 regulates liver metastases of colorectal cancer cells through the activation of EMT, and that patients with low DYRK2-expressing colorectal cancer liver metastases had worse outcomes than those with high DYRK2-expressing metastases. (PMID:28502078)
• The expression level of DYRK2 was positively correlated with glioma pathological grade. (PMID:28677030)
• Results provide evidence that DYRK2 suppresses the proliferation of breast cancer cells and invasion through CDK14 expression. (PMID:29193658)
• found that liver cancer patients with low DYRK2 expression had a significantly shorter overall survival (PMID:30851422)
• DYRK2 is strongly activated in normal or early-stage tumor cells, where they effectively degrade Snail through betaTrCP-mediated ubiquitination, thus suppressing epithelial-mesenchymal transition. (PMID:31209060)
• Especially in tumor cells, accumulating studies have revealed the molecular mechanisms of DYRK2 from the aspect of apoptosis, proliferation, EMT, and stem- ness. Considering in vitro and xenograft studies as well as down-regulation of DYRK2 in tumor specimens, DYRK2 is an important candidate for tumor suppressor. [review] (PMID:31505048)
• DYRK2 phosphorylates NDEL1 S336 to prime the phosphorylation of NDEL1 S332 by GSK3beta. The data suggest the NDEL1 phosphorylation at S336/S332 by the TARA-DYRK2-GSK3beta complex as a novel regulatory mechanism underlying neuronal morphogenesis. (PMID:31815665)
• Impairment of DYRK2 by DNMT1mediated transcription augments carcinogenesis in human colorectal cancer. (PMID:32236621)
• Frequent DYRK2 gene amplification in micropapillary element of lung adenocarcinoma - an implication in progression in EGFR-mutated lung adenocarcinoma. (PMID:33368138)
• Emerging roles of DYRK2 in cancer. (PMID:33376136)
• Combination of DYRK2 and TERT Expression Is a Powerful Predictive Marker for Early-stage Breast Cancer Recurrence. (PMID:35347031)
• Selective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry. (PMID:35439114)
• Dual inhibition of HSF1 and DYRK2 impedes cancer progression. (PMID:36622366)
• FBXW7 tumor suppressor regulation by dualspecificity tyrosine-regulated kinase 2. (PMID:36934104)
• Dual-specificity tyrosine-regulated kinase 2 exerts anti-tumor effects by induction of G1 arrest in lung adenocarcinoma. (PMID:38508285)
• Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase. (PMID:38968120)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dyrk2	ENSDARG00000094646
mus_musculus	Dyrk2	ENSMUSG00000028630
rattus_norvegicus	Dyrk2	ENSRNOG00000007821
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), HIPK3 (ENSG00000110422), CLK4 (ENSG00000113240), DYRK3 (ENSG00000143479), DYRK1A (ENSG00000157540), HIPK4 (ENSG00000160396), HIPK1 (ENSG00000163349), CLK2 (ENSG00000176444), CLK3 (ENSG00000179335)

Protein

Protein identifiers

Dual specificity tyrosine-phosphorylation-regulated kinase 2 — Q92630 (reviewed: Q92630)

All UniProt accessions (4): Q92630, A0A0A0MR56, F5GXG1, F5H5L5

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at ‘Ser-46’, and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at ‘Ser-544’, enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at ‘Ser-641’, and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at ‘Ser-457’, promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro).

Subunit / interactions. Component of an E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 (EDVP complex). Interacts directly with EDD/UBR5, DDB1 and DCAF1. Interacts with SIAH2 and MDM2. Interacts with MAP3K10 and NFATC1. May also interact with CCNL2.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Testis, after the onset of spermatogenesis.

Post-translational modifications. Autophosphorylates cotranslationally on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop, but once mature, does not have any protein tyrosine kinase activity. Phosphorylated at Thr-106 and Ser-442 by ATM in response to genotoxic stress. Under normal conditions, polyubiquitinated in the nucleus by MDM2, leading to its proteasomal degradation. Phosphorylation on Thr-106 and Ser-442 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation. Polyubiquitinated by SIAH2, leading to its proteasomal degradation. Polyubiquitinated by SIAH2 occurs under normal conditions, and is enhanced in response to hypoxia.

Activity regulation. Activated by autophosphorylation on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop. Inhibited by acridine analogs, purvalanol, and barely by harmine. Inhibited by leucettine and leucettine derivatives.

Induction. Accumulates in nucleus upon DNA damage. Induced in both esophageal and lung adenocarcinomas.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92630-1	1	yes
Q92630-2	2

RefSeq proteins (2): NP_003574, NP_006473* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR042521	DYRK	Homologous_superfamily
IPR050494	Ser_Thr_dual-spec_kinase	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.12.1 — dual-specificity kinase (BRENDA: 51 organisms, 125 substrates, 188 inhibitors, 14 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.019–0.1185	7
HISTONE H1	0.006–0.012	5

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (67 total): helix 21, strand 15, modified residue 6, sequence variant 6, turn 5, mutagenesis site 4, binding site 3, chain 1, domain 1, splice variant 1, region of interest 1, sequence conflict 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
5LXC	X-RAY DIFFRACTION	2.15
7DH9	X-RAY DIFFRACTION	2.19
6HDR	X-RAY DIFFRACTION	2.2
3KVW	X-RAY DIFFRACTION	2.28
6HDP	X-RAY DIFFRACTION	2.3
7DH3	X-RAY DIFFRACTION	2.33
7DHK	X-RAY DIFFRACTION	2.34
6K0J	X-RAY DIFFRACTION	2.35
3K2L	X-RAY DIFFRACTION	2.36
7DHN	X-RAY DIFFRACTION	2.38
7DHH	X-RAY DIFFRACTION	2.49
5ZTN	X-RAY DIFFRACTION	2.5
7DJO	X-RAY DIFFRACTION	2.5
7EJV	X-RAY DIFFRACTION	2.5
4AZF	X-RAY DIFFRACTION	2.55
5LXD	X-RAY DIFFRACTION	2.58
7DG4	X-RAY DIFFRACTION	2.58
7DHC	X-RAY DIFFRACTION	2.59
7AKF	X-RAY DIFFRACTION	2.6
7DL6	X-RAY DIFFRACTION	2.65
7DHV	X-RAY DIFFRACTION	2.68
8HLT	X-RAY DIFFRACTION	2.8
7AKH	X-RAY DIFFRACTION	2.85
9MC0	X-RAY DIFFRACTION	2.87
9KQY	X-RAY DIFFRACTION	3.2
7DHO	X-RAY DIFFRACTION	3.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92630-F1	77.04	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 348 (proton acceptor)

Ligand- & substrate-binding residues (3): 228–236; 251; 301–304

Post-translational modifications (6): 381, 382, 442, 449, 30, 106

Mutagenesis-validated functional residues (4):

Position	Phenotype
106	impaired atm-mediated phosphorylation, reduced affinity with mdm2 and altered mdm2-triggered ubiquitination.
189–191	impaired nuclear translocation.
251	abolishes protein serine/threonine kinase activity.
442	impaired atm-mediated phosphorylation, reduced affinity with mdm2 and altered mdm2-triggered ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation

MSigDB gene sets: 379 (showing top): GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, TAATAAT_MIR126, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, MORF_CDK2, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MAHAJAN_RESPONSE_TO_IL1A_DN, BROWNE_HCMV_INFECTION_48HR_DN, HOFMANN_MYELODYSPLASTIC_SYNDROM_RISK_DN, GOBP_POSITIVE_REGULATION_OF_GLYCOGEN_METABOLIC_PROCESS, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN

GO Biological Process (8): protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), smoothened signaling pathway (GO:0007224), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), positive regulation of glycogen biosynthetic process (GO:0045725), negative regulation of calcineurin-NFAT signaling cascade (GO:0070885), regulation of signal transduction by p53 class mediator (GO:1901796), apoptotic process (GO:0006915)

GO Molecular Function (12): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), manganese ion binding (GO:0030145), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), ribonucleoprotein complex (GO:1990904), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of TP53 Activity	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
cellular anatomical structure	4
phosphorylation	1
protein modification process	1
cellular response to stress	1
cell surface receptor signaling pathway	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
glycogen biosynthetic process	1
regulation of glycogen biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of glycogen metabolic process	1
calcineurin-NFAT signaling cascade	1
regulation of calcineurin-NFAT signaling cascade	1
negative regulation of calcineurin-mediated signaling	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1841 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYRK2	DDB1	Q16531	785
DYRK2	DCAF1	Q9Y4B6	737
DYRK2	UBR5	O95071	706
DYRK2	TP53AIP1	Q9HCN2	622
DYRK2	CCDC71	Q8IV32	599
DYRK2	SLC13A5	Q86YT5	582
DYRK2	SP3	Q02447	536
DYRK2	PSMC4	P43686	518
DYRK2	SRSF7	Q16629	516
DYRK2	ANTXR2	P58335	511
DYRK2	GSK3B	P49841	511
DYRK2	NFATC2	Q13469	507
DYRK2	RCAN1	P53805	506
DYRK2	HASPIN	Q8TF76	489
DYRK2	ALK	Q9UM73	466

IntAct

49 interactions, top by confidence:

A	B	Type	Score
DYRK2	DYRK4	psi-mi:“MI:0915”(physical association)	0.570
DYRK4	DYRK2	psi-mi:“MI:0915”(physical association)	0.570
DYRK2	WDR62	psi-mi:“MI:0915”(physical association)	0.560
DYRK2	SP100	psi-mi:“MI:0915”(physical association)	0.560
IKZF1	DYRK2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB9	DYRK2	psi-mi:“MI:0915”(physical association)	0.560
KXD1	DYRK2	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	DYRK2	psi-mi:“MI:0915”(physical association)	0.560
WDR62	DYRK2	psi-mi:“MI:0915”(physical association)	0.560
SP100	DYRK2	psi-mi:“MI:0915”(physical association)	0.560
DYRK2	KXD1	psi-mi:“MI:0915”(physical association)	0.560
DYRK2	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
DYRK2	ZBTB9	psi-mi:“MI:0915”(physical association)	0.560
DYRK2	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
DYRK2	YWHAE	psi-mi:“MI:0915”(physical association)	0.400
SFN	DYRK2	psi-mi:“MI:0915”(physical association)	0.400
DYRK2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
DYRK2	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
RTN1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CLK2	PRPF4	psi-mi:“MI:0914”(association)	0.350
DYRK2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350

BioGRID (225): DYRK2 (Two-hybrid), IKZF1 (Two-hybrid), KXD1 (Two-hybrid), LZTS2 (Two-hybrid), ZBTB9 (Two-hybrid), WDR62 (Two-hybrid), UBE2D1 (Reconstituted Complex), RAD54B (Two-hybrid), DCAF5 (Affinity Capture-MS), DYRK2 (Reconstituted Complex), TBK1 (Affinity Capture-Western), DYRK2 (Affinity Capture-Western), DYRK2 (Affinity Capture-Western), RNF8 (Affinity Capture-Western), DYRK2 (Affinity Capture-MS)

ESM2 similar proteins: A0A194VNL2, A4QXX4, B0WAU8, B0XPE4, G4N6Z6, G4N7X0, G5EFU0, G5EGQ3, H2L099, O24527, O42626, O96013, P0C198, P0CP70, P0CP71, P0CS76, P0CS77, P0DP15, P11837, P32490, P32491, P38679, P48479, Q0UY20, Q16W24, Q17850, Q19469, Q23356, Q2GYV9, Q2ULU3, Q2VWQ3, Q4P5N0, Q4WHP3, Q4WJJ0, Q501Q9, Q5B4Z3, Q5BBL3, Q5U4C9, Q754N7, Q75DK7

Diamond homologs: A4L9P5, A8WJR8, A8X4H1, A8X5H5, B3WFY8, G5EDB2, O14132, O23145, O43781, O55076, O76039, O88850, O88904, P14680, P18265, P18431, P20911, P22518, P24941, P43288, P43289, P48963, P49657, P49759, P49840, P50613, P51136, P51567, P51568, P51952, P83102, Q00526, Q03147, Q04859, Q07538, Q08DZ2, Q09690, Q09815, Q0IJ08, Q10156

SIGNOR signaling

38 interactions.

A	Effect	B	Mechanism
DYRK2	unknown	CARHSP1	phosphorylation
DYRK2	“up-regulates activity”	DPYSL3	phosphorylation
DYRK2	up-regulates	TP53	phosphorylation
DYRK2	down-regulates	JUN	phosphorylation
DYRK2	up-regulates	SIAH2	phosphorylation
DYRK2	“down-regulates quantity by destabilization”	KATNA1	phosphorylation
DYRK2	“up-regulates activity”	EDVP	binding
DYRK2	“down-regulates quantity by destabilization”	CDC25A	phosphorylation
DYRK2	“down-regulates quantity by destabilization”	TBK1	phosphorylation
CDC25A	“down-regulates activity”	DYRK2	dephosphorylation
DYRK2	“up-regulates activity”	HSF1	phosphorylation
DYRK2	“down-regulates quantity by destabilization”	GLI2	phosphorylation
DYRK2	“down-regulates quantity by destabilization”	NOTCH1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Membrane Trafficking	5	8.8×	5e-03
Vesicle-mediated transport	5	8.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein autophosphorylation	5	23.4×	1e-03
protein phosphorylation	5	11.0×	8e-03
protein stabilization	5	10.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

68 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

601 predictions. Top by Δscore:

Variant	Effect	Δscore
12:67649785:C:G	acceptor_gain	1.0000
12:67649178:GACCG:G	donor_gain	0.9900
12:67649180:CCGGT:C	donor_loss	0.9900
12:67649181:CGGTA:C	donor_loss	0.9900
12:67649183:G:GG	donor_gain	0.9900
12:67649183:GTAA:G	donor_loss	0.9900
12:67649184:T:G	donor_loss	0.9900
12:67649784:AC:A	acceptor_gain	0.9900
12:67649784:ACGT:A	acceptor_gain	0.9900
12:67649784:ACGTG:A	acceptor_gain	0.9900
12:67649785:C:CA	acceptor_gain	0.9900
12:67649787:T:TA	acceptor_gain	0.9900
12:67650792:G:GT	donor_gain	0.9900
12:67657085:T:G	acceptor_gain	0.9900
12:67657087:T:G	acceptor_gain	0.9900
12:67657092:T:A	acceptor_gain	0.9900
12:67657096:T:A	acceptor_gain	0.9900
12:67649188:G:GT	donor_gain	0.9800
12:67649700:G:GT	donor_gain	0.9800
12:67649784:A:AG	acceptor_gain	0.9800
12:67649788:G:A	acceptor_gain	0.9800
12:67653629:G:T	donor_gain	0.9800
12:67657086:A:AG	acceptor_gain	0.9800
12:67657099:A:AG	acceptor_gain	0.9800
12:67657102:CCA:C	acceptor_loss	0.9800
12:67657103:CAG:C	acceptor_loss	0.9800
12:67657104:AG:A	acceptor_loss	0.9800
12:67657104:AGATT:A	acceptor_gain	0.9800
12:67657105:G:A	acceptor_loss	0.9800
12:67657105:GATTG:G	acceptor_gain	0.9800

AlphaMissense

3952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:67657517:G:C	D204H	1.000
12:67657569:G:T	R221M	1.000
12:67657592:G:A	G229R	1.000
12:67657592:G:C	G229R	1.000
12:67657592:G:T	G229W	1.000
12:67657593:G:A	G229E	1.000
12:67657593:G:T	G229V	1.000
12:67657598:G:A	G231R	1.000
12:67657598:G:C	G231R	1.000
12:67657598:G:T	G231W	1.000
12:67657599:G:A	G231E	1.000
12:67657599:G:C	G231A	1.000
12:67657599:G:T	G231V	1.000
12:67657601:A:C	S232R	1.000
12:67657603:C:A	S232R	1.000
12:67657603:C:G	S232R	1.000
12:67657604:T:A	F233I	1.000
12:67657604:T:C	F233L	1.000
12:67657604:T:G	F233V	1.000
12:67657605:T:C	F233S	1.000
12:67657605:T:G	F233C	1.000
12:67657606:T:A	F233L	1.000
12:67657606:T:G	F233L	1.000
12:67657607:G:A	G234R	1.000
12:67657607:G:C	G234R	1.000
12:67657607:G:T	G234W	1.000
12:67657608:G:A	G234E	1.000
12:67657608:G:T	G234V	1.000
12:67657613:G:C	V236L	1.000
12:67657613:G:T	V236L	1.000

dbSNP variants (sampled 300 via entrez): RS1000225280 (12:67647477 C>G), RS1000252230 (12:67653159 C>G), RS1000316208 (12:67649566 C>T), RS1000946321 (12:67664681 G>A,T), RS1001100183 (12:67657867 C>T), RS1001175726 (12:67654399 C>A,T), RS1001318511 (12:67648773 C>G), RS1001327793 (12:67660083 T>A,G), RS1001349531 (12:67648899 C>G,T), RS1001375983 (12:67653476 T>C), RS1001397955 (12:67647754 G>C,T), RS1001408912 (12:67653685 G>A), RS1001654677 (12:67659669 A>C,G), RS1001846954 (12:67665332 T>C), RS1002050723 (12:67665501 T>C,G)

Disease associations

OMIM: gene MIM:603496 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003518_36	Daytime sleep phenotypes	9.000000e-06
GCST004791_3	Amyotrophic lateral sclerosis (C9orf72 mutation interaction)	3.000000e-06
GCST004861_12	Itch intensity from mosquito bite	2.000000e-20
GCST004862_200	Itch intensity from mosquito bite adjusted by bite size	6.000000e-07
GCST004862_97	Itch intensity from mosquito bite adjusted by bite size	4.000000e-11
GCST004863_36	Mosquito bite size	1.000000e-12
GCST004865_10	Itch intensity from mosquito bite adjusted by bite size	9.000000e-10
GCST005752_57	Systemic lupus erythematosus	2.000000e-07
GCST009391_801	Metabolite levels	2.000000e-06
GCST010725_21	Malaria	8.000000e-06
GCST010725_35	Malaria	9.000000e-06
GCST012434_5	Peak height velocity	6.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0010396	sphingomyelin 22:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4376 (SINGLE PROTEIN), CHEMBL5739547 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

30 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 379,065 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL140	CURCUMIN	3	93,882
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL4297639	LORECIVIVINT	3	282
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1614713	CC-401	2	389
CHEMBL1721885	SU-014813	2	363
CHEMBL230011	TG100-115	2	1,504
CHEMBL3989870	BERZOSERTIB	2	1,265
CHEMBL445813	AT-7519	2	2,614
CHEMBL4462530	ZEMIRCICLIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL521851	PICTILISIB	2
CHEMBL1908397	KW-2449	1
CHEMBL269538	HARMINE	1
CHEMBL296468	BMS-387032	1
CHEMBL4784318	CIRTUVIVINT	1
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1
CHEMBL574738	AST-487	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Dyrk2 subfamily

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
leucettine L41	Inhibition	9.46	pIC50
compound 5b [PMID: 24900464]	Inhibition	7.22	pIC50
compound 3b [PMID: 23454515]	Inhibition	6.89	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
HS38	IC50	200 nM

ChEMBL bioactivities

643 potent at pChembl≥5 of 649 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CHEMBL5289179
9.00	IC50	1	nM	CHEMBL5084504
8.70	IC50	2	nM	CHEMBL5090676
8.70	IC50	2	nM	CIRTUVIVINT
8.60	IC50	2.5	nM	CURCUMIN
8.52	IC50	3	nM	CHEMBL4460561
8.50	IC50	3.16	nM	CHEMBL3894571
8.40	IC50	4	nM	CHEMBL5077927
8.40	IC50	4	nM	CHEMBL5286478
8.30	IC50	5	nM	CHEMBL5089294
8.30	IC50	5	nM	CURCUMIN
8.22	IC50	6	nM	CHEMBL5094409
8.22	IC50	6	nM	CHEMBL5073976
8.22	IC50	6	nM	CHEMBL5070553
8.10	IC50	8	nM	CHEMBL5091510
8.10	IC50	8	nM	CHEMBL5195216
8.10	IC50	8	nM	CHEMBL5414801
8.06	IC50	8.8	nM	CHEMBL5070553
8.05	IC50	9	nM	CHEMBL5072926
8.05	IC50	9	nM	CHEMBL5088511
8.00	IC50	10	nM	CHEMBL5080497
8.00	IC50	10	nM	CHEMBL4441878
8.00	IC50	10	nM	CHEMBL5422486
8.00	IC50	10	nM	CURCUMIN
7.97	IC50	10.8	nM	CHEMBL2386747
7.96	IC50	11	nM	CHEMBL5181008
7.96	IC50	11	nM	CHEMBL1803085
7.96	IC50	11	nM	CHEMBL5405059
7.89	IC50	13	nM	CHEMBL5095897
7.89	IC50	13	nM	CHEMBL5438158
7.85	IC50	14	nM	CHEMBL5082044
7.85	IC50	14	nM	CHEMBL5083159
7.85	IC50	14	nM	CHEMBL1802358
7.85	IC50	14	nM	CHEMBL5419098
7.85	IC50	14.18	nM	CHEMBL5574295
7.82	IC50	15	nM	CHEMBL5200518
7.82	IC50	15	nM	CHEMBL5272300
7.82	IC50	15	nM	CHEMBL5416942
7.82	IC50	15	nM	CHEMBL5395194
7.81	IC50	15.6	nM	CHEMBL5081787
7.80	IC50	16	nM	CHEMBL3589661
7.80	IC50	16	nM	CHEMBL5278493
7.80	IC50	16	nM	CHEMBL5417147
7.80	IC50	16	nM	CHEMBL5428132
7.76	IC50	17.5	nM	CHEMBL5095897
7.72	IC50	19	nM	CHEMBL1254460
7.70	IC50	20	nM	CHEMBL5073598
7.70	IC50	20	nM	CHEMBL5088687
7.68	IC50	21	nM	CHEMBL5073869
7.66	IC50	22	nM	CHEMBL5071425

PubChem BioAssay actives

635 with measured affinity, of 1622 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[6-[[4-(1,3-benzothiazol-5-yl)-5-fluoropyrimidin-2-yl]amino]-3-pyridinyl]-piperazin-1-ylmethanone;hydrochloride	1947261: Inhibition of hexa His-tagged DYRK2 (72 to 479 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as substrate phosphorylation using 4E-BP1 as substrate in presence of [gamma33-P]ATP incubated for 2 hrs by scintillation counter analysis	ic50	0.0006	uM
4-(3-cyclopentyl-2-methylimidazo[4,5-b]pyridin-5-yl)pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0010	uM
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	1851277: Inhibition of DYRK2 (unknown origin)	ic50	0.0020	uM
4-[2-methyl-4-(1,3-thiazol-5-ylmethoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]pyridin-2-amine	1812162: Inhibition of DYRK2 (unknown origin) by TR FRET assay	ic50	0.0020	uM
Curcumin	1947260: Inhibition of human GST-tagged DYRK2 expressed in Escherichia coli BL21 (DE3) using woodtide as substrate in presence of [gamma33-P]ATP incubated for 30 mins by Scintillation counter analysis	ic50	0.0025	uM
4-(3-cyclopropyl-2-methylimidazo[4,5-b]pyridin-5-yl)pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0030	uM
methyl 9-(2-fluoro-4-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714129: Inhibition of DYRK2 (unknown origin)	ic50	0.0032	uM
4-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0040	uM
[5-[[4-(1,3-benzothiazol-5-yl)-5-fluoropyrimidin-2-yl]amino]-2-pyridinyl]-piperazin-1-ylmethanone;hydrochloride	1947261: Inhibition of hexa His-tagged DYRK2 (72 to 479 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as substrate phosphorylation using 4E-BP1 as substrate in presence of [gamma33-P]ATP incubated for 2 hrs by scintillation counter analysis	ic50	0.0040	uM
4-[3-(3-methoxypropyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0050	uM
4-[3-[2-(furan-2-yl)ethyl]-2-methylimidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0060	uM
4-[2-methyl-3-(2,2,2-trifluoroethyl)imidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0060	uM
4-(3-tert-butyl-2-methylimidazo[4,5-b]pyridin-5-yl)pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0060	uM
4-[2-methyl-4-(thiophen-3-ylmethoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]pyridin-2-amine	1812162: Inhibition of DYRK2 (unknown origin) by TR FRET assay	ic50	0.0080	uM
(4Z)-4-(1,4-benzodioxin-3-ylmethylidene)-2-[4-(4-methylpiperazin-1-yl)anilino]-1H-imidazol-5-one	1871887: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method	ic50	0.0080	uM
(4Z)-4-(2,3-dihydro-1,4-benzodioxin-6-ylmethylidene)-2-[4-(4-methylpiperazin-1-yl)anilino]-1H-imidazol-5-one	2010392: Inhibition of human DYRK2 using RBERIRStide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0080	uM
4-[2-methyl-3-(2-phenoxyethyl)imidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0090	uM
4-[3-(2-cyclohexylethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0090	uM
4-[2-methyl-3-(4,4,4-trifluorobutyl)imidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0100	uM
4-(2-methyl-3-propan-2-ylimidazo[4,5-b]pyridin-5-yl)pyridine-2,6-diamine	1947684: Inhibition of recombinant human DYRK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0100	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3,5,7-trifluoro-1-adamantyl)imino]imidazolidin-4-one	2010392: Inhibition of human DYRK2 using RBERIRStide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0100	uM
methyl 9-(2,4-dichloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714129: Inhibition of DYRK2 (unknown origin)	ic50	0.0108	uM
(4Z)-4-(1,3-benzodioxol-5-ylmethylidene)-2-(4-hydroxyanilino)-1H-imidazol-5-one	1871887: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method	ic50	0.0110	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-hydroxy-1-adamantyl)imino]imidazolidin-4-one	2010392: Inhibition of human DYRK2 using RBERIRStide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0110	uM
(4Z)-4-(1,3-benzodioxol-5-ylmethylidene)-2-(3-fluoro-4-hydroxyanilino)-1H-imidazol-5-one	1871887: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method	ic50	0.0110	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-fluoro-1-adamantyl)imino]imidazolidin-4-one	2010392: Inhibition of human DYRK2 using RBERIRStide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0130	uM
3-(2,7-dimethoxyacridin-9-yl)sulfanylpropan-1-amine	1924114: Inhibition of human DYRK2	ic50	0.0130	uM
(4Z)-2-anilino-4-(1,3-benzodioxol-5-ylmethylidene)-1H-imidazol-5-one	1871887: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method	ic50	0.0140	uM
5-(2-amino-4-pyridinyl)-2-methyl-N-(thiophen-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812156: Inhibition of DYRK2 (unknown origin) by ADP hunter plus assay	ic50	0.0140	uM
5-(2-amino-4-pyridinyl)-2-methyl-N-(thiophen-3-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812156: Inhibition of DYRK2 (unknown origin) by ADP hunter plus assay	ic50	0.0140	uM
cyclopropyl-[4-[6-[[4-[2-(diethylamino)-1,3-benzothiazol-6-yl]-5-fluoropyrimidin-2-yl]amino]pyridine-3-carbonyl]piperazin-1-yl]methanone	2024021: Inhibition of DYRK2 (unknown origin) incubated for 120 mins in presence of 33P-ATP	ic50	0.0140	uM
(2S)-2-[[6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]-2-phenylethanol	2110572: Inhibition of DYRK2 (unknown origin) preincubated with enzyme for 10 mins followed by substrate and ATP addition measured after 60 mins by ADP-Glo reagent based assay	ic50	0.0142	uM
(4Z)-4-[(4-hydroxy-3-methoxyphenyl)methylidene]-2-[4-(4-methylpiperazin-1-yl)anilino]-1H-imidazol-5-one	1871887: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method	ic50	0.0150	uM
[5-[[4-(1,3-benzothiazol-5-yl)-5-fluoropyrimidin-2-yl]amino]-2-pyridinyl]-(4-ethylpiperazin-1-yl)methanone	1947261: Inhibition of hexa His-tagged DYRK2 (72 to 479 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as substrate phosphorylation using 4E-BP1 as substrate in presence of [gamma33-P]ATP incubated for 2 hrs by scintillation counter analysis	ic50	0.0150	uM
1-[4-[6-[[4-[2-(diethylamino)-1,3-benzothiazol-6-yl]-5-fluoropyrimidin-2-yl]amino]pyridine-3-carbonyl]piperazin-1-yl]ethanone	2024021: Inhibition of DYRK2 (unknown origin) incubated for 120 mins in presence of 33P-ATP	ic50	0.0150	uM
(4Z)-4-[(3-hydroxy-4-methoxyphenyl)methylidene]-2-[4-(4-methylpiperazin-1-yl)anilino]-1H-imidazol-5-one	2010392: Inhibition of human DYRK2 using RBERIRStide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0150	uM
(5Z)-2-(2,6-dichlorophenyl)imino-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidin-4-one	1947684: Inhibition of recombinant human DYRK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0156	uM
10-bromo-11H-indolo[3,2-c]quinoline-6-carboxylic acid	1232290: Inhibition of human recombinant DYRK2 expressed in Escherichia coli using RS peptide as substrate	ic50	0.0160	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-methoxy-1-adamantyl)imino]imidazolidin-4-one	2010392: Inhibition of human DYRK2 using RBERIRStide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0160	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2S)-2-hydroxy-2-phenylethyl]iminoimidazolidin-4-one	2010392: Inhibition of human DYRK2 using RBERIRStide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0160	uM
tert-butyl 4-[5-[[4-(1,3-benzothiazol-5-yl)-5-fluoropyrimidin-2-yl]amino]pyridine-2-carbonyl]piperazine-1-carboxylate	1947261: Inhibition of hexa His-tagged DYRK2 (72 to 479 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as substrate phosphorylation using 4E-BP1 as substrate in presence of [gamma33-P]ATP incubated for 2 hrs by scintillation counter analysis	ic50	0.0160	uM
(3E,5E)-3,5-bis[(2-chlorophenyl)methylidene]piperidin-4-one	2144552: Inhibition of human recombinant DYRK2 using KKISGRLSPIMTEQ as substrate incubated for 60 mins in the presence of ATP by ADP-Glo kinase assay	ic50	0.0190	uM
5-(2-amino-4-pyridinyl)-N-[(3-fluoro-2-pyridinyl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812162: Inhibition of DYRK2 (unknown origin) by TR FRET assay	ic50	0.0200	uM
5-(2-aminopyrimidin-4-yl)-N-[(2,6-difluorophenyl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812162: Inhibition of DYRK2 (unknown origin) by TR FRET assay	ic50	0.0200	uM
4-(2,3-dimethyl-1-benzofuran-5-yl)pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0210	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507907: Binding affinity to DYRK2	kd	0.0220	uM
4-[2-methyl-3-[(2S)-2-phenoxypropyl]imidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1820105: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay	ic50	0.0220	uM
(5Z)-5-(1,3-benzodioxol-5-ylmethylidene)-2-(2,5-dimethylphenyl)iminoimidazolidin-4-one	1871887: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method	ic50	0.0220	uM
[6-[[4-(1,3-benzothiazol-5-yl)-5-fluoropyrimidin-2-yl]amino]-3-pyridinyl]-(4-ethylpiperazin-1-yl)methanone	1947261: Inhibition of hexa His-tagged DYRK2 (72 to 479 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as substrate phosphorylation using 4E-BP1 as substrate in presence of [gamma33-P]ATP incubated for 2 hrs by scintillation counter analysis	ic50	0.0220	uM
10-bromo-3-methoxy-11H-indolo[3,2-c]quinoline-6-carboxylic acid	1232290: Inhibition of human recombinant DYRK2 expressed in Escherichia coli using RS peptide as substrate	ic50	0.0230	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
Benzo(a)pyrene	affects methylation	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Formaldehyde	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
multi-kinase inhibitor 108600	decreases activity	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
4-nitrobenzaldehyde	affects binding, decreases activity	1
5-iodotubercidin	decreases activity	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	increases activity, decreases expression	1
((5Z)5-(1,3-benzodioxol-5-yl)methylene-2-phenylamino-3,5-dihydro-4H-imidazol-4-one)	decreases reaction, increases phosphorylation	1
Valsartan	decreases reaction, increases expression	1
Irinotecan	decreases expression	1
Resveratrol	decreases expression, increases expression, affects cotreatment	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases expression	1
Acetaminophen	decreases expression	1
Curcumin	affects binding, decreases activity	1
Demecolcine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1

ChEMBL screening assays

368 unique, capped per target: 362 binding, 3 admet, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003336	Binding	Inhibition of DYRK2 at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL4263639	ADMET	Inhibition of recombinant human Dyrk2 (unknown origin) at 2 uM by Lantha-screen assay	Development of novel 2,4-bispyridyl thiophene-based compounds as highly potent and selective Dyrk1A inhibitors. Part I: Benzamide and benzylamide derivatives. — Eur J Med Chem
CHEMBL5444976	Functional	Affinity Phenotypic Cellular interaction: (MTT assay (cellular toxicity in MDA-MB-231 cells, 72h treatment)) EUB0000008b DYRK2	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1LP	HyCyte KYSE-150 KO-hDYRK2	Cancer cell line	Female
CVCL_SL24	HAP1 DYRK2 (-) 1	Cancer cell line	Male
CVCL_SL25	HAP1 DYRK2 (-) 2	Cancer cell line	Male
CVCL_SL26	HAP1 DYRK2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.