DYRK1A

Summary

DYRK1A (dual specificity tyrosine phosphorylation regulated kinase 1A, HGNC:3091) is a protein-coding gene on chromosome 21q22.13, encoding Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Q13627). Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. It is a selective cancer dependency (DepMap: 10.5% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene. It is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5’ UTR or in the 3’ coding region. These variants encode at least five different isoforms.

Source: NCBI Gene 1859 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 1,185 total — 195 pathogenic, 62 likely-pathogenic
• Phenotypes (HPO): 160
• Druggable target: yes — 48 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 10.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001347721

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3091
Approved symbol	DYRK1A
Name	dual specificity tyrosine phosphorylation regulated kinase 1A
Location	21q22.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157540
Ensembl biotype	protein_coding
OMIM	600855
Entrez	1859

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 23 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000338785, ENST00000398956, ENST00000398960, ENST00000426672, ENST00000455097, ENST00000462274, ENST00000642309, ENST00000643355, ENST00000643551, ENST00000643624, ENST00000643808, ENST00000643854, ENST00000644367, ENST00000644942, ENST00000645424, ENST00000645774, ENST00000646224, ENST00000646351, ENST00000646523, ENST00000646548, ENST00000647188, ENST00000647425, ENST00000647504, ENST00000865096, ENST00000865097, ENST00000865098, ENST00000865099, ENST00000865100, ENST00000919132

RefSeq mRNA: 7 — MANE Select: NM_001347721 NM_001347721, NM_001347722, NM_001347723, NM_001396, NM_101395, NM_130436, NM_130438

CCDS: CCDS13653, CCDS13654, CCDS42925, CCDS42926, CCDS86987

Canonical transcript exons

ENST00000647188 — 12 exons

Exon	Start	End
ENSE00001033275	37493017	37493163
ENSE00001033292	37506099	37506223
ENSE00001033294	37496118	37496258
ENSE00001033299	37486467	37486614
ENSE00001262033	37505283	37505589
ENSE00003459385	37478208	37478300
ENSE00003504646	37472684	37472880
ENSE00003584551	37480638	37480826
ENSE00003636141	37490175	37490461
ENSE00003818253	37366773	37367628
ENSE00003827888	37511911	37526358
ENSE00003829613	37420299	37420384

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.0770 / max 431.3695, expressed in 1812 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189034	8.9364	1710
189039	7.1287	1649
189037	2.4366	971
189033	1.7501	1005
189032	0.9525	657
189040	0.6852	343
189050	0.6799	340
189038	0.3221	119
189041	0.1854	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	97.85	gold quality
biceps brachii	UBERON:0001507	97.80	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.52	gold quality
bronchial epithelial cell	CL:0002328	97.38	gold quality
tibialis anterior	UBERON:0001385	97.33	gold quality
middle temporal gyrus	UBERON:0002771	97.31	gold quality
germinal epithelium of ovary	UBERON:0001304	97.23	gold quality
visceral pleura	UBERON:0002401	97.21	gold quality
trabecular bone tissue	UBERON:0002483	97.15	gold quality
calcaneal tendon	UBERON:0003701	97.14	gold quality
endothelial cell	CL:0000115	97.08	gold quality
deltoid	UBERON:0001476	97.07	gold quality
pleura	UBERON:0000977	96.97	gold quality
caput epididymis	UBERON:0004358	96.92	gold quality
parietal pleura	UBERON:0002400	96.88	gold quality
skin of hip	UBERON:0001554	96.77	gold quality
cauda epididymis	UBERON:0004360	96.76	gold quality
pigmented layer of retina	UBERON:0001782	96.65	gold quality
gluteal muscle	UBERON:0002000	96.65	gold quality
blood vessel layer	UBERON:0004797	96.62	gold quality
tibia	UBERON:0000979	96.60	gold quality
upper leg skin	UBERON:0004262	96.55	gold quality
choroid plexus epithelium	UBERON:0003911	96.46	gold quality
corpus epididymis	UBERON:0004359	96.37	gold quality
cerebellar vermis	UBERON:0004720	96.36	gold quality
vastus lateralis	UBERON:0001379	96.33	gold quality
quadriceps femoris	UBERON:0001377	96.31	gold quality
palpebral conjunctiva	UBERON:0001812	96.24	gold quality
bone marrow	UBERON:0002371	96.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, REST

miRNA regulators (miRDB)

239 targeting DYRK1A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 10.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• DYRK1A protein kinase may play a role in regulating the biogenesis of the splicing speckle compartment (PMID:12799418)
• Overexpression of DYRK1A induces multinucleation through overduplication of the centrosome during interphase. (PMID:12964950)
• characterize cyclin L2 as a highly mobile component of nuclear speckles and suggest that DYRK1A may regulate splicing by phosphorylation of cyclin L2 (PMID:14623875)
• In this review experimental evidence is compiled and discussed which supports the involvement of MNB/DYRK1A in several neuropathologies and cognitive deficits of Down syndrome. (PMID:15068245)
• Although the function of MNB/DYRK1A in intracellular signalling and regulation of cell function is still poorly defined, current evidence in this review suggests that MNB/DYRK1A kinase may play a role in the regulation of gene expression. (PMID:15068246)
• Neurons were the only cells showing the presence of Mnb kinase in both cell nucleus and cytoplasm. Nuclear localization supports the concept that Mnb may be involved in control of gene expression. (PMID:15126119)
• encodes a serine-threonine kinase but despite its potential involvement in the neurobiological alterations associated with Down syndrome (PMID:15694837)
• DYRK1A may play a critical role in Ras-dependent transducing signals that are required for promoting or maintaining neuronal differentiation (PMID:15917294)
• The present observations indicate modifications in the expression of constitutive Dyrk1A in the cytoplasm and nuclei of neurons in various neurodegenerative diseases associated with tau phosphorylation. (PMID:16242644)
• Mnb/Dyrk1A is responsible for in vivo phosphorylation of amphiphysin I at serine-293. (PMID:16733250)
• There is now compelling evidence that the protein products of two genes on chromosome 21, Down syndrome candidate region 1 (DSCR1) and dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), interact functionally. (PMID:16919501)
• Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD. (PMID:17135279)
• in DS subjects, the brain levels of DYRK1A protein were increased approximately 1.5-fold, indicating that this protein is overexpressed in gene dosage-dependent manner. (PMID:17145134)
• DYRK1A autophosphorylates, via an intramolecular mechanism, on Ser-520, this phosphorylation allows the binding of 14-3-3beta, which in turn stimulates the catalytic activity of DYRK1A (PMID:17229891)
• raised Dyrk1a in HPV16 immortalized keratinocytes and cervical lesions may serve as a candidate antiapoptotic factor in the FKHR regulated pathway and initiate immortalization and tumorigenesis gradually (PMID:17294446)
• DYRK does not require tyrosine phosphorylation for activity in vitro. (PMID:17536841)
• DYRK1A has a role in the hyperphosphorylation of Tau and an extra copy of the DYRK1A gene contributes to the early onset of Alzheimer disease (PMID:17906291)
• Over-expression of DYRK1A in Down syndrome may play a role in accelerating Alzheimer’s disease pathogenesis through phosphorylation of beta-amyloid precursor protein (APP). (PMID:18005339)
• Use DYRK1A transgenic mice as a model for partial trisomy 21 and determine changes in brain volume. (PMID:18231969)
• The regulatory effect of E2F1 suggests that DYRK1A may play a role in cell cycle regulation or apoptosis. (PMID:18366763)
• truncating mutations of DYRK1A result in a clinical phenotype including microcephaly. (PMID:18405873)
• Results suggest that DYRK1A increases the transforming potential of HPV16-infected cells because of the greater stability of HPV16E7. (PMID:18468476)
• Dyrk1A-induced tau phosphorylation inhibited its biological activity & promoted self-aggregation. findings suggest novel mechanism by which overexpression of Dyrk1A in Down syndrome brain causes neurofibrillary degeneration via hyperphosphorylation. (PMID:18509201)
• Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration (PMID:18658135)
• DYRK1A interacts and phosphorylates the RTK negative regulator Sprouty-2 (PMID:18678649)
• DYRK1A is involved in nerve degeneration and that overexpression of this kinase may contribute to the early onset of these pathologies in Down syndrome. (PMID:18696092)
• DYRK1A-mediated deregulation of REST is a very early pathological consequence of trisomy 21 with potential to disturb the development of all embryonic lineages. (PMID:18771760)
• Regulation of apoptosis through inhibitory phosphorylation of caspase 9 may play a role in the function of DYRK1A during development and in pathogenesis. (PMID:19016842)
• DYRK1A regulates caspase-9-mediated apoptosis during retina development (PMID:19081073)
• Epigallocatechin gallate is a specific and safe DYRK1A inhibitor (PMID:19242551)
• DYRK1A attenuates Notch signalling in neural cells, constituting a novel mechanism to modulate different developmental processes and contribute to the alterations observed during brain development in animal models of Down syndrome. (PMID:19383720)
• Data show that forced expression of NFATc1 induced DYRK1A expression, suggesting a negative feedback loop. (PMID:19801542)
• Our negative findings in the Spanish population argue against the hypothesis that DYRK1A genetic variations are causally related to Alzheimer’s disease risk (PMID:19995442)
• DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. (PMID:20167603)
• Dyrk1A overexpression inhibits transgenic neural cell proliferation and promotes premature neuronal differentiation in the developing cerebral cortex without affecting cell fate and layer positioning. (PMID:20237271)
• These results reveal a potential regulatory link between Dyrk1A and presenilin 1 in the amyloid beta pathway of Down syndrome and Alzheimer disease brains (PMID:20456003)
• up-regulation of Dyrk1A contributes to altered neuronal proliferation in DS through specific phosphorylation of p53 at Ser-15 and subsequent p21(CIP1) induction. (PMID:20696760)
• Study shows that miR-199b is a direct calcineurin/NFAT target gene that increases in expression in mouse and human heart failure, and targets the nuclear NFAT kinase dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a (Dyrk1a) (PMID:21102440)
• REVIEW: Activation, regulation, and inhibition of DYRK1A (PMID:21126318)
• The inhibitory effect of Dyrk1A on synaptic vesicle endocytosis is confirmed in neuronal cultures derived from transgenic mice overexpressing Dyrk1A at levels found in Down syndrome. (PMID:21135538)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	dyrk1ab	ENSDARG00000023814
danio_rerio	dyrk1aa	ENSDARG00000063570
mus_musculus	Dyrk1a	ENSMUSG00000022897
rattus_norvegicus	Dyrk1a	ENSRNOG00000001662
drosophila_melanogaster	mnb	FBGN0259168
caenorhabditis_elegans		WBGENE00003149
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), HIPK3 (ENSG00000110422), CLK4 (ENSG00000113240), DYRK2 (ENSG00000127334), DYRK3 (ENSG00000143479), HIPK4 (ENSG00000160396), HIPK1 (ENSG00000163349), CLK2 (ENSG00000176444), CLK3 (ENSG00000179335)

Protein

Protein identifiers

Dual specificity tyrosine-phosphorylation-regulated kinase 1A — Q13627 (reviewed: Q13627)

Alternative names: Dual specificity YAK1-related kinase, HP86, Protein kinase minibrain homolog

All UniProt accessions (8): Q13627, A0A2R8Y443, A0A2R8Y6I6, A0A2R8Y6L5, A0A2R8YDF3, A0A2R8YEY4, E7EMI5, N0GVR9

UniProt curated annotations — full annotation on UniProt →

Function. Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Exhibits a substrate preference for proline at position P+1 and arginine at position P-3. Plays an important role in double-strand breaks (DSBs) repair following DNA damage. Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A. May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6. Has pro-survival function and negatively regulates the apoptotic process. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits p53/TP53 activity and apoptosis. Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at ‘Thr-434’.

Subunit / interactions. Interacts with RAD54L2/ARIP4. Interacts with CRY2. Interacts with RANBP9. Interacts with WDR68. Interacts with SIRT1. (Microbial infection) Interacts with human adenovirus 5 E1A protein.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Ubiquitous. Highest levels in skeletal muscle, testis, fetal lung and fetal kidney.

Post-translational modifications. Autophosphorylated on numerous tyrosine residues. Can also autophosphorylate on serine and threonine residues (in vitro).

Disease relevance. Intellectual developmental disorder, autosomal dominant 7 (MRD7) [MIM:614104] A disease characterized by primary microcephaly, severe intellectual disability without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Intellectual disability is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by RANBP9. Inhibited by harmine, leucettamine B and leucettine L41.

Domain organisation. The polyhistidine repeats act as targeting signals to nuclear speckles. The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance its ability to phosphorylate the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II).

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q13627-1	Long	yes
Q13627-2	1
Q13627-3	2
Q13627-4	3
Q13627-5	4

RefSeq proteins (7): NP_001334650, NP_001334651, NP_001334652, NP_001387, NP_567824, NP_569120, NP_569122 (=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
IPR044131	PKc_DYR1A/1B	Domain
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), 4 shown:

• [DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H(+) (RHEA:10216)
• 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 (97 total): helix 19, modified residue 16, strand 12, turn 9, sequence conflict 8, compositionally biased region 7, region of interest 7, splice variant 7, binding site 3, sequence variant 3, mutagenesis site 2, chain 1, domain 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

91 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6S14	X-RAY DIFFRACTION	1.05
6S1H	X-RAY DIFFRACTION	1.05
6S17	X-RAY DIFFRACTION	1.1
6S1B	X-RAY DIFFRACTION	1.3
4YLK	X-RAY DIFFRACTION	1.4
4YLL	X-RAY DIFFRACTION	1.4
6S1J	X-RAY DIFFRACTION	1.41
6A1F	X-RAY DIFFRACTION	1.5
7A4R	X-RAY DIFFRACTION	1.8
7A5D	X-RAY DIFFRACTION	1.8
7O7K	X-RAY DIFFRACTION	1.82
8T2H	X-RAY DIFFRACTION	1.85
7A4O	X-RAY DIFFRACTION	1.9
7A4Z	X-RAY DIFFRACTION	1.9
7A51	X-RAY DIFFRACTION	1.9
7AKA	X-RAY DIFFRACTION	1.9
7AJ4	X-RAY DIFFRACTION	2
7AJ5	X-RAY DIFFRACTION	2
7AJ8	X-RAY DIFFRACTION	2
7AKL	X-RAY DIFFRACTION	2
8C3R	X-RAY DIFFRACTION	2.06
8C3G	X-RAY DIFFRACTION	2.08
7A52	X-RAY DIFFRACTION	2.1
7A5L	X-RAY DIFFRACTION	2.1
7AJ2	X-RAY DIFFRACTION	2.1
7AJV	X-RAY DIFFRACTION	2.1
7AK2	X-RAY DIFFRACTION	2.1
5A4T	X-RAY DIFFRACTION	2.15
6A1G	X-RAY DIFFRACTION	2.15
7AJS	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13627-F1	67.73	0.44

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): 287 (proton acceptor)

Ligand- & substrate-binding residues (3): 165–173; 188; 238–241

Post-translational modifications (16): 14, 111, 140, 145, 159, 177, 219, 310, 319, 321, 402, 449, 529, 538, 748, 758

Mutagenesis-validated functional residues (2):

Position	Phenotype
188	abolished protein kinase activity.
321	mildly reduces kinase activity. does not abolish autophosphorylation on tyrosine residues.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1538133	G0 and Early G1

MSigDB gene sets: 0 (showing top):

GO Biological Process (18): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), protein phosphorylation (GO:0006468), nervous system development (GO:0007399), circadian rhythm (GO:0007623), peptidyl-tyrosine phosphorylation (GO:0018108), negative regulation of microtubule polymerization (GO:0031115), negative regulation of heterochromatin formation (GO:0031452), positive regulation of RNA splicing (GO:0033120), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), positive regulation of DNA-templated transcription (GO:0045893), protein autophosphorylation (GO:0046777), negative regulation of mRNA splicing, via spliceosome (GO:0048025), regulation of amyloid-beta formation (GO:1902003), regulation of neurofibrillary tangle assembly (GO:1902996), double-strand break repair via homologous recombination (GO:0000724), double-strand break repair via nonhomologous end joining (GO:0006303), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (21): transcription coactivator activity (GO:0003713), actin binding (GO:0003779), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), cytoskeletal protein binding (GO:0008092), RNA polymerase II CTD heptapeptide repeat kinase activity (GO:0008353), tubulin binding (GO:0015631), identical protein binding (GO:0042802), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), protein serine kinase activity (GO:0106310), histone H3T45 kinase activity (GO:0140857), splicing factor binding (GO:1990935), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (13): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), nuclear speck (GO:0016607), axon (GO:0030424), dendrite (GO:0030425), ribonucleoprotein complex (GO:1990904), cytoskeleton (GO:0005856), microtubule (GO:0005874), neurofilament (GO:0005883), actin filament (GO:0005884)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitotic G1 phase and G1/S transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
cytoskeletal protein binding	3
protein binding	3
protein serine/threonine kinase activity	3
cellular anatomical structure	3
regulation of mRNA splicing, via spliceosome	2
protein phosphorylation	2
positive regulation of gene expression	2
regulation of DNA-templated transcription	2
double-strand break repair	2
cytoplasm	2
neuron projection	2
polymeric cytoskeletal fiber	2
alternative mRNA splicing, via spliceosome	1
phosphorylation	1
protein modification process	1
system development	1
rhythmic process	1
peptidyl-tyrosine modification	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
negative regulation of protein polymerization	1
microtubule polymerization	1
negative regulation of supramolecular fiber organization	1
regulation of heterochromatin formation	1
heterochromatin formation	1
negative regulation of heterochromatin organization	1
RNA splicing	1
regulation of RNA splicing	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
negative regulation of signal transduction by p53 class mediator	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
mRNA splicing, via spliceosome	1
negative regulation of RNA splicing	1
negative regulation of mRNA processing	1
amyloid-beta formation	1
regulation of amyloid precursor protein catabolic process	1
regulation of inclusion body assembly	1

Protein interactions and networks

STRING

3210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYRK1A	DCAF7	P61962	938
DYRK1A	RCAN1	P53805	874
DYRK1A	NFATC1	O95644	817
DYRK1A	CADPS2	Q86UW7	811
DYRK1A	REST	Q13127	791
DYRK1A	AUTS2	Q8WXX7	788
DYRK1A	GSK3B	P49841	783
DYRK1A	APP	P05067	735
DYRK1A	NRG3	P56975	712
DYRK1A	SLC13A5	Q86YT5	702
DYRK1A	SYNJ1	O43426	696
DYRK1A	NFATC2	Q13469	680
DYRK1A	IQGAP1	P46940	661
DYRK1A	RAD54L2	Q9Y4B4	654
DYRK1A	CCNT1	O60563	651

IntAct

258 interactions, top by confidence:

A	B	Type	Score
DYRK1A	DCAF7	psi-mi:“MI:0915”(physical association)	0.940
KIF24	CCP110	psi-mi:“MI:0914”(association)	0.810
CTBP1	ZEB2	psi-mi:“MI:0914”(association)	0.800
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
FAM117B	DCAF7	psi-mi:“MI:0914”(association)	0.730
DCAF7	DIAPH1	psi-mi:“MI:0914”(association)	0.730
DYRK1A	RB1	psi-mi:“MI:0914”(association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
DCAF7	PFDN6	psi-mi:“MI:2364”(proximity)	0.570
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
DYRK1A	KPRP	psi-mi:“MI:0915”(physical association)	0.560
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
FOXR2	MYC	psi-mi:“MI:0914”(association)	0.530
EP300	DYRK1A	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
FNTB	BLTP3B	psi-mi:“MI:0914”(association)	0.530
FANCD2OS	CNOT1	psi-mi:“MI:0914”(association)	0.530
FAM117B	GAPDHS	psi-mi:“MI:0914”(association)	0.530
DCAF7	CLASP2	psi-mi:“MI:0914”(association)	0.510
IGF2BP1	DYRK1A	psi-mi:“MI:0915”(physical association)	0.500
IGF2BP2	DYRK1A	psi-mi:“MI:0915”(physical association)	0.500
FMR1	DYRK1A	psi-mi:“MI:0915”(physical association)	0.500
DYRK1A	IGF2BP3	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (1441): DYRK1A (Affinity Capture-RNA), DYRK1A (Affinity Capture-RNA), DYRK1A (Reconstituted Complex), Sirt1 (Biochemical Activity), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), DCAF7 (Affinity Capture-Western), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), DYRK1A (Affinity Capture-MS)

ESM2 similar proteins: A8WJR8, A8WYE4, A8X4H1, O45797, O74526, P13185, P13186, P14680, P22211, P22987, P31034, P39073, P46551, P48479, P49657, P49762, P53739, P53894, Q09690, Q0IJ08, Q13627, Q19469, Q23977, Q2TAE3, Q2ULU3, Q4P9T2, Q4WHP3, Q5AP53, Q5U4C9, Q61214, Q63470, Q6C3D7, Q6CR51, Q6FKC6, Q6FP74, Q751F5, Q754N7, Q75D46, Q75DK7, Q7RZD3

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

71 interactions.

A	Effect	B	Mechanism
DYRK1A	up-regulates	RCAN1	phosphorylation
DYRK1A	“down-regulates activity”	FOXO1	phosphorylation
DYRK1A	“down-regulates activity”	FOXO3	phosphorylation
DYRK1A	“up-regulates activity”	DYRK1A	phosphorylation
DYRK1A	down-regulates	AMPH	phosphorylation
DYRK1A	down-regulates	DNM1	phosphorylation
DYRK1A	unknown	SF3B1	phosphorylation
DYRK1A	“down-regulates activity”	AMPH	phosphorylation
DYRK1A	up-regulates	SNCA	phosphorylation
DYRK1A	up-regulates	TP53	phosphorylation
DYRK1A	down-regulates	MAPT	phosphorylation
DYRK1A	unknown	SRSF1	phosphorylation
DYRK1A	down-regulates	SPRY2	phosphorylation
DYRK1A	down-regulates	FOXO1	phosphorylation
DYRK1A	down-regulates	FOXO3	phosphorylation
DYRK1A	down-regulates	FOXO4	phosphorylation
DYRK1A	down-regulates	FOXO6	phosphorylation
DYRK1A	down-regulates	NOTCH1	phosphorylation
DYRK1A	down-regulates	CCND1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	29.2×	1e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	29.2×	1e-05
Activation of BAD and translocation to mitochondria	5	27.6×	1e-04
Activation of BH3-only proteins	5	18.0×	6e-04
Molecules associated with elastic fibres	6	13.4×	6e-04
FOXO-mediated transcription	5	12.2×	2e-03
RHO GTPases activate PKNs	5	11.5×	2e-03
Intrinsic Pathway for Apoptosis	5	10.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
substantia nigra development	6	12.0×	8e-03
receptor-mediated endocytosis	7	8.5×	9e-03
nervous system development	16	4.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1185 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	195
Likely pathogenic	62
Uncertain significance	354
Likely benign	371
Benign	83

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1015236	NM_001347721.2(DYRK1A):c.833A>G (p.Asp278Gly)	Pathogenic
1068692	NM_001347721.2(DYRK1A):c.763A>T (p.Lys255Ter)	Pathogenic
1073604	NC_000021.8:g.(?38844966)(38845202_?)del	Pathogenic
1073605	NC_000021.8:g.(?38844966)(38884854_?)del	Pathogenic
1076837	NM_001347721.2(DYRK1A):c.331C>T (p.Gln111Ter)	Pathogenic
1162312	NM_001347721.2(DYRK1A):c.977del (p.Gly326fs)	Pathogenic
1162313	NM_001347721.2(DYRK1A):c.924+1G>C	Pathogenic
1162314	NM_001347721.2(DYRK1A):c.450del (p.Arg149_Tyr150insTer)	Pathogenic
1162315	NM_001347721.2(DYRK1A):c.1951del (p.Ser651fs)	Pathogenic
1162316	NM_001347721.2(DYRK1A):c.1243del (p.His415fs)	Pathogenic
1162711	NM_001347721.2(DYRK1A):c.1006del (p.Trp336fs)	Pathogenic
1162778	NM_001347721.2(DYRK1A):c.772C>T (p.Gln258Ter)	Pathogenic
1164088	NM_001347721.2(DYRK1A):c.909T>A (p.Cys303Ter)	Pathogenic
1172635	NM_001347721.2(DYRK1A):c.300+846A>G	Pathogenic
1184904	NM_001347721.2(DYRK1A):c.1112del (p.Pro371fs)	Pathogenic
1254755	NM_001347721.2(DYRK1A):c.1190_1193del (p.Lys397fs)	Pathogenic
1275809	NM_001347721.2(DYRK1A):c.1743dup (p.Val582fs)	Pathogenic
1299504	NM_001347721.2(DYRK1A):c.433_439del (p.Lys145fs)	Pathogenic
1320058	NM_001347721.2(DYRK1A):c.637+2dup	Pathogenic
1340074	GRCh37/hg19 21q22.13(chr21:38721309-38803816)x1	Pathogenic
1374418	NM_001347721.2(DYRK1A):c.748_749del (p.Leu250fs)	Pathogenic
1388377	NM_001347721.2(DYRK1A):c.1699C>T (p.Gln567Ter)	Pathogenic
1396925	NM_001347721.2(DYRK1A):c.293_294dup (p.Asn99fs)	Pathogenic
1425863	NM_001347721.2(DYRK1A):c.1158dup (p.Glu387Ter)	Pathogenic
1436085	NM_001347721.2(DYRK1A):c.210dup (p.Arg71fs)	Pathogenic
1457564	NM_001347721.2(DYRK1A):c.267_268dup (p.Asp90fs)	Pathogenic
162152	NM_001347721.2(DYRK1A):c.736C>T (p.Arg246Ter)	Pathogenic
162153	NM_001347721.2(DYRK1A):c.586C>T (p.Arg196Ter)	Pathogenic
162154	NM_001347721.2(DYRK1A):c.594_597delinsGAA (p.Glu199fs)	Pathogenic
162156	NM_001347721.2(DYRK1A):c.918dup (p.Gln307fs)	Pathogenic

SpliceAI

2667 predictions. Top by Δscore:

Variant	Effect	Δscore
21:37472679:TGTAG:T	acceptor_loss	1.0000
21:37472680:GTAGG:G	acceptor_loss	1.0000
21:37472682:A:AG	acceptor_gain	1.0000
21:37472682:AGG:A	acceptor_loss	1.0000
21:37472683:G:GT	acceptor_gain	1.0000
21:37472683:GGA:G	acceptor_gain	1.0000
21:37472879:AGG:A	donor_loss	1.0000
21:37472881:G:GG	donor_gain	1.0000
21:37472881:GTAA:G	donor_loss	1.0000
21:37472882:T:A	donor_loss	1.0000
21:37478206:A:AG	acceptor_gain	1.0000
21:37478207:G:GG	acceptor_gain	1.0000
21:37478207:GA:G	acceptor_gain	1.0000
21:37478297:TGAGG:T	donor_loss	1.0000
21:37478299:AGGTA:A	donor_loss	1.0000
21:37478300:GGTAA:G	donor_loss	1.0000
21:37478301:GT:G	donor_loss	1.0000
21:37478302:T:A	donor_loss	1.0000
21:37480631:A:AG	acceptor_gain	1.0000
21:37480633:TTCA:T	acceptor_loss	1.0000
21:37480635:CAGGT:C	acceptor_loss	1.0000
21:37480636:A:AG	acceptor_gain	1.0000
21:37480636:AG:A	acceptor_gain	1.0000
21:37480637:G:GA	acceptor_gain	1.0000
21:37480637:GG:G	acceptor_gain	1.0000
21:37480637:GGT:G	acceptor_gain	1.0000
21:37480637:GGTT:G	acceptor_gain	1.0000
21:37480637:GGTTT:G	acceptor_gain	1.0000
21:37480823:ACAG:A	donor_loss	1.0000
21:37480824:CAG:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000007525 (21:37429472 A>C), RS1000008440 (21:37390567 G>A), RS1000013447 (21:37396682 A>G), RS1000017060 (21:37377192 T>C), RS1000017242 (21:37448669 A>G), RS1000040732 (21:37464115 T>A), RS1000046182 (21:37505966 C>A,G,T), RS1000069125 (21:37520073 A>C,G), RS1000070665 (21:37511429 T>G), RS1000078077 (21:37391721 C>G,T), RS1000096595 (21:37520321 A>C), RS1000100833 (21:37467469 G>A,C,T), RS1000125703 (21:37512900 T>A), RS1000173080 (21:37468481 A>G), RS1000178898 (21:37479505 CAA>C)

Disease associations

OMIM: gene MIM:600855 | disease phenotypes: MIM:614104

GenCC curated gene-disease

Disease	Classification	Inheritance
DYRK1A-related intellectual disability syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (9): DYRK1A-related intellectual disability syndrome (MONDO:0013578), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), enophthalmos (MONDO:0001210), autism spectrum disorder (MONDO:0005258), microphthalmia (MONDO:0021129), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092), intellectual disability syndrome due to a DYRK1A point mutation (MONDO:0018733)

Orphanet (6): DYRK1A-related intellectual disability syndrome (Orphanet:464306), Non-specific syndromic intellectual disability (Orphanet:528084), Male infertility with spermatogenesis disorder (Orphanet:399775), Intellectual disability syndrome due to a DYRK1A point mutation (Orphanet:464311), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

160 total (30 of 160 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000041	Chordee
HP:0000047	Hypospadias
HP:0000049	Shawl scrotum
HP:0000054	Micropenis
HP:0000107	Renal cyst
HP:0000119	Abnormality of the genitourinary system
HP:0000122	Unilateral renal agenesis
HP:0000125	Pelvic kidney
HP:0000126	Hydronephrosis
HP:0000179	Thick lower lip vermilion
HP:0000185	Cleft soft palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000269	Prominent occiput
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000319	Smooth philtrum
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000411	Protruding ear
HP:0000414	Bulbous nose

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000753_18	Metabolic syndrome	6.000000e-06
GCST000990_1	HIV-1 replication	5.000000e-06
GCST007248_3	Stroke	6.000000e-09
GCST009325_66	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	3.000000e-11
GCST010991_48	Parkinson’s disease	5.000000e-08
GCST011687_9	Systolic blood pressure	3.000000e-08
GCST90002379_169	Basophil count	3.000000e-19
GCST90002380_66	Basophil percentage of white cells	2.000000e-11
GCST90002381_269	Eosinophil count	1.000000e-24
GCST90002382_545	Eosinophil percentage of white cells	4.000000e-15
GCST90002390_683	Mean corpuscular hemoglobin	4.000000e-10
GCST90002396_75	Mean reticulocyte volume	1.000000e-09
GCST90002397_297	Mean spheric corpuscular volume	3.000000e-10
GCST90002398_63	Neutrophil count	4.000000e-12
GCST90002407_179	White blood cell count	5.000000e-15

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0000195	metabolic syndrome
EFO:0004343	waist-hip ratio
EFO:0000180	HIV-1 infection
EFO:0006335	systolic blood pressure
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D015841	Enophthalmos	C11.675.319
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D008850	Microphthalmos	C11.250.566; C16.131.384.666
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2292 (SINGLE PROTEIN), CHEMBL6195513 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195553 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

48 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 314,233 (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
CHEMBL1094636	NIRAPARIB	4	6,433
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2005186	BELUMOSUDIL	4	1,817
CHEMBL2105712	AFATINIB DIMALEATE	4	3,215
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL415049	BARASERTIB	3	2,371
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL4297639	LORECIVIVINT	3	282
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230165	SILMITASERTIB	2
CHEMBL14762	SELICICLIB	2
CHEMBL1614713	CC-401	2
CHEMBL1721885	SU-014813	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL230011	TG100-115	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL3218578	BGT-226 FREE BASE	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Dyrk1 subfamily

Most potent curated ligand interactions (15 total), top 15:

Ligand	Action	Affinity	Parameter
leucettine L41	Inhibition	10.4	pIC50
compound 68 [PMID: 24900699]	Inhibition	9.8	pIC50
compound 72 [WO2013026806]	Inhibition	9.66	pIC50
cirtuvivint	Inhibition	9.0	pIC50
compound 17 [PMID: 23642479]	Inhibition	8.4	pIC50
GNF4877	Inhibition	8.22	pIC50
GNF2133	Inhibition	8.21	pIC50
compound 2-2c [PMID: 32003560]	Inhibition	7.6	pIC50
lorecivivint	Inhibition	7.57	pIC50
compound 3b [PMID: 23454515]	Inhibition	7.55	pIC50
harmine	Inhibition	7.48	pIC50
KH-CB19	Inhibition	7.26	pIC50
ML315	Inhibition	6.55	pIC50
epigallocatechin-3-gallate	Inhibition	6.48	pIC50
(S)-CR8	Inhibition	6.05	pIC50

Binding affinities (BindingDB)

1086 measured of 1214 human assays (1216 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl 9-(2-bromo-4-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.16 nM	US-9446044: DYRK1 inhibitors and uses thereof
4-[[4-methoxy-5-(3-methylbenzotriazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1-methylcyclohexan-1-ol	EC50	0.2 nM	US-20250129104: 7H-PYRROLO[2,3-D]PYRIMIDINES AND PREPARATION AND USES THEREOF
methyl 9-(2,4-dichloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.22 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(2-fluoro-4-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.36 nM	US-9446044: DYRK1 inhibitors and uses thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-2-piperazin-1-ylpyridine-4-carboxamide	EC50	0.4 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methyltriazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[2-(4-methylpiperazin-1-yl)-4-pyridinyl]-5-quinolin-6-yl-7H-pyrrolo[2,3-d]pyrimidin-2-amine	EC50	0.5 nM	US-20250129104: 7H-PYRROLO[2,3-D]PYRIMIDINES AND PREPARATION AND USES THEREOF
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-2-(4-propan-2-ylpiperazin-1-yl)pyridine-4-carboxamide	EC50	0.6 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-hydroxyethyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.6 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-methoxy-5-(3-methylbenzotriazol-5-yl)-N-[(1R,5S)-3-oxabicyclo[3.1.0]hexan-6-yl]-7H-pyrrolo[2,3-d]pyrimidin-2-amine	EC50	0.6 nM	US-20250129104: 7H-PYRROLO[2,3-D]PYRIMIDINES AND PREPARATION AND USES THEREOF
2-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.7 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(4-methylpiperazin-1-yl)-N-[6-(1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.7 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-methoxy-N-(4-methoxycyclohexyl)-5-quinoxalin-6-yl-7H-pyrrolo[2,3-d]pyrimidin-2-amine	EC50	0.7 nM	US-20250129104: 7H-PYRROLO[2,3-D]PYRIMIDINES AND PREPARATION AND USES THEREOF
1-methyl-4-[[5-(3-methylbenzotriazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]cyclohexan-1-ol	EC50	0.7 nM	US-20250129104: 7H-PYRROLO[2,3-D]PYRIMIDINES AND PREPARATION AND USES THEREOF
2-(4-methylpiperazin-1-yl)-N-[6-(1H-pyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(2,7-diazaspiro[3.5]nonan-2-yl)-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-methyl-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-1,3-dihydroisoindole-5-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
6-(4-methylpiperazin-1-yl)-N-[6-(1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]pyridine-3-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-methoxy-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.8 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-pyridin-4-yl-5-quinolin-6-yl-7H-pyrrolo[2,3-d]pyrimidin-2-amine	EC50	0.8 nM	US-20250129104: 7H-PYRROLO[2,3-D]PYRIMIDINES AND PREPARATION AND USES THEREOF
3-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(1-methylpiperidin-4-yl)oxy-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
6-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-3-carboxamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-2-(4-methylpiperazin-1-yl)pyridine-4-carboxamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
3-(1-methylpiperidin-4-yl)oxy-N-[6-(1,3-oxazol-5-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(1-methylpiperidin-4-yl)oxy-N-[6-(1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-(3,3,3-trifluoropropyl)piperidine-4-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(hydroxymethyl)-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(dimethylamino)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-pyrrolidin-1-ylacetyl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-methoxy-N-[(1R,5S)-3-oxabicyclo[3.1.0]hexan-6-yl]-5-pyrazolo[1,5-a]pyridin-5-yl-7H-pyrrolo[2,3-d]pyrimidin-2-amine	EC50	0.9 nM	US-20250129104: 7H-PYRROLO[2,3-D]PYRIMIDINES AND PREPARATION AND USES THEREOF
methyl 9-(2,4-difluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.94 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(4-methylanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.98 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(4-chloro-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.99 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(2,7-diazaspiro[3.5]nonan-2-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
6-(4-methylpiperazin-1-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]pyridine-3-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(4-methylpiperazin-1-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-cyano-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-[(3-fluoroazetidin-1-yl)methyl]-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(oxetan-3-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
3-(1-methylpiperidin-4-yl)oxy-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]benzamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-2-piperidin-4-yloxypyridine-4-carboxamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-fluoro-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]benzamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-[4-(dimethylamino)piperidin-1-yl]-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-2-morpholin-4-ylpyridine-4-carboxamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(4-cyclopropylpiperazin-1-yl)-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)-N-[6-(1,3-oxazol-5-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-[3-(dimethylamino)azetidin-1-yl]-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(4-propan-2-ylpiperazin-1-yl)-N-[6-(1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.17	Kd	0.067	nM	CHEMBL4647659
10.12	Kd	0.075	nM	CHEMBL4644916
10.07	Kd	0.086	nM	CHEMBL5070553
10.05	Kd	0.09	nM	CHEMBL393525
10.00	Kd	0.101	nM	CHEMBL5285332
9.92	Kd	0.12	nM	CHEMBL3688339
9.80	IC50	0.16	nM	CHEMBL2386744
9.80	IC50	0.16	nM	CHEMBL2386770
9.80	Kd	0.16	nM	CHEMBL4647416
9.79	Kd	0.163	nM	CIRTUVIVINT
9.73	Kd	0.188	nM	CHEMBL4441878
9.66	IC50	0.22	nM	CHEMBL2386747
9.66	Kd	0.22	nM	CHEMBL4645393
9.62	Kd	0.24	nM	CHEMBL5093650
9.62	Kd	0.24	nM	CHEMBL4848254
9.60	Kd	0.252	nM	CHEMBL5081787
9.57	IC50	0.27	nM	CHEMBL5575038
9.57	IC50	0.2692	nM	CHEMBL5575038
9.56	Kd	0.276	nM	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-
9.55	Kd	0.283	nM	CHEMBL5289681
9.54	Kd	0.292	nM	CHEMBL5091238
9.52	IC50	0.3	nM	CHEMBL1946917
9.49	IC50	0.32	nM	CHEMBL5575589
9.49	IC50	0.3236	nM	CHEMBL5575589
9.48	IC50	0.33	nM	CHEMBL5569968
9.47	IC50	0.34	nM	CHEMBL5567566
9.47	IC50	0.3388	nM	CHEMBL5567566
9.44	IC50	0.36	nM	CHEMBL2386745
9.44	IC50	0.36	nM	CHEMBL3894571
9.43	IC50	0.37	nM	CHEMBL5572106
9.43	IC50	0.3715	nM	CHEMBL5572106
9.40	EC50	0.4	nM	CHEMBL5895786
9.40	EC50	0.4	nM	CHEMBL5973318
9.40	Ki	0.3981	nM	CHEMBL1980407
9.36	IC50	0.44	nM	CHEMBL5574654
9.36	IC50	0.44	nM	CHEMBL5575553
9.36	IC50	0.44	nM	CHEMBL5569075
9.36	IC50	0.4365	nM	CHEMBL5574654
9.36	IC50	0.4365	nM	CHEMBL5575553
9.36	IC50	0.4365	nM	CHEMBL5569075
9.31	IC50	0.49	nM	CHEMBL5575017
9.31	IC50	0.4898	nM	CHEMBL5575017
9.30	Kd	0.5	nM	CHEMBL4764647
9.30	Kd	0.5	nM	CHEMBL4779510
9.30	Kd	0.5	nM	CHEMBL4783719
9.30	Kd	0.5	nM	CHEMBL4752512
9.30	Kd	0.5	nM	CHEMBL4740866
9.30	Kd	0.5	nM	CHEMBL4796768
9.30	Kd	0.5	nM	CHEMBL4781621
9.30	Kd	0.5	nM	CHEMBL4757202

PubChem BioAssay actives

1945 with measured affinity, of 5156 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
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0001	uM
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-methylsulfonylpiperidine-4-carboxamide	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0001	uM
4-[2-methyl-3-(2,2,2-trifluoroethyl)imidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0001	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1650171: Binding affinity to wild-type human partial length DYRK1A (H129 to S509 residues) expressed in mammalian expression system by Kinomescan method	kd	0.0001	uM
(3R)-1-[3-[[3-amino-6-(2-fluoro-5-propan-2-yloxyphenyl)pyrazine-2-carbonyl]amino]-4-pyridinyl]piperidine-3-carboxylic acid	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0001	uM
N-butyl-6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridine-3-carboxamide	1650171: Binding affinity to wild-type human partial length DYRK1A (H129 to S509 residues) expressed in mammalian expression system by Kinomescan method	kd	0.0001	uM
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0002	uM
5-(2-amino-4-pyridinyl)-N-[(2,6-difluorophenyl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812179: Inhibition of human wild type DYRK1A (H129 to S509) expressed in mammalian cells by DiscoveryX Kinomescan binding assay	kd	0.0002	uM
4-(2-methyl-3-propan-2-ylimidazo[4,5-b]pyridin-5-yl)pyridine-2,6-diamine	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0002	uM
N,N-dimethyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0002	uM
ethyl 4-[[4-(aminomethyl)cyclohexyl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridine-3-carboxylate	1650171: Binding affinity to wild-type human partial length DYRK1A (H129 to S509 residues) expressed in mammalian expression system by Kinomescan method	kd	0.0002	uM
ethyl 6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridine-3-carboxylate	1650171: Binding affinity to wild-type human partial length DYRK1A (H129 to S509 residues) expressed in mammalian expression system by Kinomescan method	kd	0.0002	uM
methyl 9-(2,4-dichloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714121: Inhibition of human DYRK1A using [33P]-ATP incubated for 120 mins	ic50	0.0002	uM
methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748670: Inhibition of recombinant DYRK1A (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0002	uM
1-(2-methylpropyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0003	uM
(5Z)-2-(2,6-dichlorophenyl)imino-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidin-4-one	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0003	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024540: Binding affinity to human DYRK1A assessed as dissociation constant	kd	0.0003	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one	1947696: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	0.0003	uM
N-(2-fluoro-4-methoxyphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0003	uM
1-phenyl-2-[[6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]ethanol	2110526: Inhibition of DYRK1A (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	0.0003	uM
(1R)-2-[[6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]-1-phenylethanol	2110526: Inhibition of DYRK1A (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	0.0003	uM
(1R)-1-phenyl-2-[[6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]ethanol	2110526: Inhibition of DYRK1A (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	0.0003	uM
3,10-dihydroxy-7H-chromeno[3,4-b]indol-6-one	1928796: Inhibition of DYRK1A (unknown origin)	ic50	0.0003	uM
(2S)-2-phenyl-2-[[6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]ethanol	2110526: Inhibition of DYRK1A (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	0.0004	uM
N-(2,4-difluorophenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0004	uM
N-(2,4-dichlorophenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0004	uM
N-[(1R)-1-(3-fluorophenyl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0004	uM
methyl 9-(2-fluoro-4-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714121: Inhibition of human DYRK1A using [33P]-ATP incubated for 120 mins	ic50	0.0004	uM
methyl 9-(4-fluoro-2-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748670: Inhibition of recombinant DYRK1A (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0004	uM
6-(7-fluoro-6-pyridin-4-ylbenzimidazol-1-yl)pyridine-3-carboxamide	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
4-[[4-(2-methyl-5-pyridin-4-ylimidazo[4,5-b]pyridin-3-yl)phenyl]methyl]morpholine	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
4-(5-pyridin-4-ylimidazo[4,5-b]pyridin-3-yl)benzoic acid	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
1-(1,3-benzodioxol-5-yl)-7-fluoro-6-pyridin-4-ylbenzimidazole	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
4-[4-[5-(1-cyclopropylpyrazol-4-yl)-2-methylimidazo[4,5-b]pyridin-3-yl]-2-fluorophenyl]morpholine	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
methyl 4-(7-fluoro-6-pyridin-4-ylbenzimidazol-1-yl)benzoate	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
3-(1,3-benzodioxol-5-yl)-5-pyridin-4-ylimidazo[4,5-b]pyridine	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
7-(2-methyl-5-pyridin-4-ylimidazo[4,5-b]pyridin-3-yl)-4H-1,4-benzoxazin-3-one	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
1-[(1R,5S)-6-(2-methyl-5-pyridin-4-ylimidazo[4,5-b]pyridin-3-yl)-3-azabicyclo[3.1.0]hexan-3-yl]ethanone	1724882: Binding affinity to DYRK1A (unknown origin)	kd	0.0005	uM
N-[(1R)-1-phenylethyl]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0005	uM
N-phenyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0005	uM
ethyl 6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-(dimethylcarbamoyl)cyclohexyl]amino]-1,5-naphthyridine-3-carboxylate	1650171: Binding affinity to wild-type human partial length DYRK1A (H129 to S509 residues) expressed in mammalian expression system by Kinomescan method	kd	0.0006	uM
2-phenyl-2-[[6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]ethanol	2110526: Inhibition of DYRK1A (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	0.0006	uM
N-benzyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0006	uM
2,2-dimethyl-3-[[6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]propanoic acid	2110526: Inhibition of DYRK1A (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	0.0006	uM
N-[(1R)-1-(2-fluorophenyl)ethyl]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0006	uM
N-(2-phenylethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0006	uM
(2S)-2-[[6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]-2-phenylethanol	2110526: Inhibition of DYRK1A (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	0.0007	uM
(1S)-1-phenyl-2-[[6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]ethanol	2110526: Inhibition of DYRK1A (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	0.0007	uM
1-[6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]piperidine-4-carboxylic acid	2110526: Inhibition of DYRK1A (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	0.0008	uM
N-(oxan-4-ylmethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-amine	2110526: Inhibition of DYRK1A (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	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	2
Harmine	affects binding, decreases reaction, increases phosphorylation, decreases activity	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
glycyrin	decreases activity	1
licocoumarone	affects binding, decreases activity	1
multi-kinase inhibitor 108600	decreases activity, decreases expression, decreases phosphorylation	1
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
coumarin	increases phosphorylation	1
5-iodotubercidin	decreases activity	1
epigallocatechin gallate	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
licochalcone A	decreases activity	1
CGP 52608	affects binding, increases reaction	1
SU 6656	decreases activity	1
pyrazolanthrone	decreases activity	1
6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine	decreases activity	1
abrine	increases expression	1
jinfukang	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
Irinotecan	decreases expression	1
Resveratrol	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases response to substance	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1

ChEMBL screening assays

866 unique, capped per target: 855 binding, 7 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003335	Binding	Inhibition of DYRK1A at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1614148	Functional	PUBCHEM_BIOASSAY: Assay for Inhibitors of Dual-Specificity Tyrosine-(Y)-Phosphorylation Regulated Kinase 1A (Kinase-Glo assay). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1770, AID1997, AID488872, AID48888	PubChem BioAssay data set
CHEMBL4014112	ADMET	Inhibition of recombinant human DYRK1A expressed in insect cells using RRRFRPASPLRGPPK peptide as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting	Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a New Class of Autophagy Inducers. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 induced pluripotent stem cell, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5EX	FDCHi005-A	Induced pluripotent stem cell	Male
CVCL_A5EY	FDCHi005-B	Induced pluripotent stem cell	Male
CVCL_B2W5	Abcam HEK293T DYRK1A KO	Transformed cell line	Female
CVCL_D1S7	Abcam U-87MG DYRK1A KO	Cancer cell line	Male
CVCL_D6HX	FDCHi012-A	Induced pluripotent stem cell	Female
CVCL_E0CA	Ubigene HeLa DYRK1A KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders