VRK1

Summary

VRK1 (VRK serine/threonine kinase 1, HGNC:12718) is a protein-coding gene on chromosome 14q32.2, encoding Serine/threonine-protein kinase VRK1 (Q99986). Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response. It is a selective cancer dependency (DepMap: 46.9% of cell lines).

This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely expressed in human tissues and has increased expression in actively dividing cells, such as those in testis, thymus, fetal liver, and carcinomas. Its protein localizes to the nucleus and has been shown to promote the stability and nuclear accumulation of a transcriptionally active p53 molecule and, in vitro, to phosphorylate Thr18 of p53 and reduce p53 ubiquitination. This gene, therefore, may regulate cell proliferation. This protein also phosphorylates histone, casein, and the transcription factors ATF2 (activating transcription factor 2) and c-JUN.

Source: NCBI Gene 7443 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia type 1A (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 616 total — 47 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 79
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 46.9% of screened cell lines
• MANE Select transcript: NM_003384

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12718
Approved symbol	VRK1
Name	VRK serine/threonine kinase 1
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100749
Ensembl biotype	protein_coding
OMIM	602168
Entrez	7443

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 45 protein_coding, 27 nonsense_mediated_decay, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000216639, ENST00000435624, ENST00000495064, ENST00000553683, ENST00000555067, ENST00000555351, ENST00000555402, ENST00000557222, ENST00000557352, ENST00000679365, ENST00000679452, ENST00000679462, ENST00000679506, ENST00000679533, ENST00000679650, ENST00000679727, ENST00000679736, ENST00000679758, ENST00000679770, ENST00000679816, ENST00000679843, ENST00000679903, ENST00000679918, ENST00000679941, ENST00000679977, ENST00000680007, ENST00000680084, ENST00000680222, ENST00000680319, ENST00000680335, ENST00000680339, ENST00000680348, ENST00000680384, ENST00000680387, ENST00000680509, ENST00000680526, ENST00000680538, ENST00000680683, ENST00000680724, ENST00000680756, ENST00000680849, ENST00000680851, ENST00000680922, ENST00000680993, ENST00000681061, ENST00000681077, ENST00000681101, ENST00000681176, ENST00000681195, ENST00000681249, ENST00000681344, ENST00000681355, ENST00000681363, ENST00000681419, ENST00000681474, ENST00000681493, ENST00000681524, ENST00000681538, ENST00000681598, ENST00000681677, ENST00000681695, ENST00000681778, ENST00000681785, ENST00000867448, ENST00000867449, ENST00000915471, ENST00000915472, ENST00000915473, ENST00000915474, ENST00000915475, ENST00000915476, ENST00000915477, ENST00000915478, ENST00000915479, ENST00000915480, ENST00000915481, ENST00000915482, ENST00000915483, ENST00000915484, ENST00000966951

RefSeq mRNA: 3 — MANE Select: NM_003384 NM_001411051, NM_001411053, NM_003384

CCDS: CCDS91928, CCDS91929, CCDS9947

Canonical transcript exons

ENST00000216639 — 13 exons

Exon	Start	End
ENSE00000660234	96852831	96852939
ENSE00000660236	96855224	96855356
ENSE00000660237	96856130	96856250
ENSE00000660238	96856528	96856586
ENSE00000870332	96853074	96853166
ENSE00001203552	96797382	96797447
ENSE00001203554	96881177	96881609
ENSE00003484527	96847257	96847344
ENSE00003513172	96846095	96846164
ENSE00003516476	96876030	96876120
ENSE00003610936	96837762	96837817
ENSE00003629800	96833467	96833631
ENSE00003656903	96860557	96860735

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 95.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.1207 / max 585.5837, expressed in 1760 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141348	21.1207	1760

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.47	gold quality
bone marrow	UBERON:0002371	94.35	gold quality
secondary oocyte	CL:0000655	94.28	gold quality
ganglionic eminence	UBERON:0004023	94.26	gold quality
left testis	UBERON:0004533	94.18	gold quality
ventricular zone	UBERON:0003053	94.13	gold quality
right testis	UBERON:0004534	94.08	gold quality
trabecular bone tissue	UBERON:0002483	94.00	gold quality
embryo	UBERON:0000922	93.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.71	gold quality
bone element	UBERON:0001474	93.27	gold quality
testis	UBERON:0000473	93.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.19	gold quality
bone marrow cell	CL:0002092	92.61	gold quality
cortical plate	UBERON:0005343	91.66	gold quality
calcaneal tendon	UBERON:0003701	89.67	gold quality
bronchial epithelial cell	CL:0002328	88.11	gold quality
endometrium epithelium	UBERON:0004811	87.90	gold quality
mucosa of transverse colon	UBERON:0004991	87.12	gold quality
rectum	UBERON:0001052	86.57	gold quality
hair follicle	UBERON:0002073	86.10	gold quality
epithelium of bronchus	UBERON:0002031	85.94	gold quality
epithelium of nasopharynx	UBERON:0001951	85.78	gold quality
amniotic fluid	UBERON:0000173	85.76	gold quality
nasopharynx	UBERON:0001728	85.76	gold quality
monocyte	CL:0000576	85.69	gold quality
leukocyte	CL:0000738	85.62	gold quality
mononuclear cell	CL:0000842	85.54	gold quality
tendon	UBERON:0000043	85.34	gold quality
lymph node	UBERON:0000029	85.31	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.74
E-MTAB-6678	yes	4.97
E-GEOD-150728	no	4359.23
E-HCAD-6	no	383.28
E-CURD-55	no	149.87
E-CURD-112	no	2.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, TP53

miRNA regulators (miRDB)

30 targeting VRK1, 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-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-496	98.66	69.80	931
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-6777-3P	95.35	64.30	699

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 46.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• can perform the functions of B1 kinase required for vaccinia virus genome replication, most likely due to overlapping specificity for cellular and/or viral substrates (PMID:14747564)
• VRK1 phosphorylates ATF2 and is an element of a novel signaling pathway that regulates gene transcription. (PMID:15105425)
• c-Jun is phosphorylated by the human vaccinia-related kinase 1 (VRK1) and cooperates with the N-terminal kinase of c-Jun (JNK) (PMID:15378002)
• VRK1 is the first step in a new pathway regulating p53 activity during cell proliferation (PMID:15542844)
• VRK1 might play a role in cell cycle regulation and is likely to represent the beginning of a new control mechanism of cell cycle, particularly late in the G1-S phase. (PMID:16547155)
• As the amount of p53 protein increases, there is a downregulation of the VRK1 protein level independent of its promoter. (PMID:16782868)
• The different reactivity of the VRK1 protein indicates that this protein has a subcellular localization that can be regulated, thus adding an additional level of regulatory complexity to the VRK1 protein. (PMID:17617371)
• accumulation of VRK1 in tumours with mutant p53 could result in stimulation of other signalling pathways (PMID:17689819)
• These findings collectively support a role of VRK1 as a novel mitotic histone H3 kinase in mammals. (PMID:17938195)
• Small interference RNAs specific for Vrk1, was identified that reproducibly reduce viral RNA and viral protein levels in hepatitis C virus replicon-bearing cells. (PMID:17951261)
• vrk1 gene mutation can be excluded in 2 Chinese pedigrees of the first and second branchial arch syndrome. (PMID:18257281)
• VRK1 is an immediate early response gene required for entry in G1 (PMID:18286197)
• the downregulation of VRK1 protein levels, as a consequence of p53 accumulation, is thus dependent on the levels of the p300/CBP protein available for transcriptional complexes (PMID:18612383)
• Ran is a novel negative regulator of nuclear VRK1 and VRK2 kinase activity, which may vary in different subcellular localizations generating an asymmetric intracellular distribution of kinase activity depending on local protein interactions. (PMID:18617507)
• Results show that VRK1 activates CREB and regulates cell cycle progression in the DNA replication period by inducing cyclin D1 (CCND1) expression. (PMID:18713830)
• The Plk3-VRK1 kinase module might represent two consecutive steps of a signaling cascade that participates in the regulation of Golgi fragmentation. (PMID:19103756)
• Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. (PMID:19646678)
• VRK1 downregulation is necessary to modulate the block in cell cycle progression induced by p53 as part of its DNA damage response. (PMID:21386980)
• NMR solution structure of a catalytically active form of human VRK1 (PMID:21543316)
• VRK1 interacts and phosphorylates coilin, a protein regulating the assembly of Cajal bodies in the nucleus. (PMID:21920476)
• direct interaction and binding features between VRK1 and macroH2A1.2 (PMID:22194607)
• Data show that vaccinia-related kinase 1 (VRK1) in resting cells plays an important role in the formation of ionizing radiation-induced foci that assemble on the 53BP1 scaffold protein during the DNA damage response. (PMID:22621922)
• Data from molecular dynamic simulations suggest that bivalent cations play key structural roles in stabilization of VRK1/VRK2; bivalent cations have no obvious effects on VRK3. These kinases are targets in search for antineoplastic agents. [REVIEW] (PMID:23082977)
• MKP2 is a negative regulator of VRK1-mediated histone H3 phosphorylation. (PMID:23223570)
• This study identification of disease-causing alleles in 3 children from 2 unrelated families with Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly. (PMID:24126608)
• VRK1 deficiency disrupts nuclear envelope morphology and leads to BAF retention on mitotic chromosomes. (PMID:24430874)
• The VRK1-p53 basal complex is an early-warning system for immediate cellular responses to DNA damage. (PMID:24492002)
• VRK1 can contribute to make these tumors more resistant to DNA damage-based therapies, such as ionizing radiation or doxorubicin, which is consistent with its association to a poor prognosis in ER positive breast cancer. (PMID:24731990)
• VRK1 deficiency in human and mouse leads to downregulation of amyloid-beta precursor protein (APP). APP overexpression rescues the phenotype caused by Vrk1 knockdown, suggesting that VRK1 affects neuronal migration through an APP-dependent mechanism. (PMID:25609612)
• VRK1 is a novel chromatin component that reacts to its alterations and participates very early in DNA damage response, functioning by itself or in cooperation with Ataxia Telangiectasia Mutated Proteins. (PMID:25923214)
• VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics. (PMID:26068304)
• VRK1 may act as a tumor promoter by controlling the level of cell cycle regulators associated with G1/S transition and could potentially serve as a therapeutic target and/or prognostic biomarker for HCC. (PMID:26375549)
• we conclude that VRK1 may be a candidate prognostic biomarker as well as a potential therapeutical target of hepatocellular carcinoma (PMID:26706601)
• VRK1 regulation of NBS1 contributes to the stability of the repair complex and permits the sequential steps in DNA damage response. (PMID:26869104)
• VRK1 was lowly expressed in adherent MM cells and highly expressed in suspended cells. In addition, VRK1 was positively correlated with the proliferation of MM cells by regulating the expression of cell cycle-related protein, such as cyclinD1, CDK2 and p27(kip1). (PMID:27319807)
• Block the activation of the VRK1 promoter by Sox2. (PMID:27334688)
• VRK1 AND VRK2 expression are predictive of tumor response to neoadjuvant chemoradiation therapy in rectal adenocarcinoma. (PMID:27456229)
• VRK1 and BANF1 yielded AUCs of 0.790 and 0.735, respectively. (PMID:28298069)
• Structural characterization of human vaccinia-related kinases, VRK1 and VRK2, bound to small-molecule inhibitors, has been reported. (PMID:28790404)
• this study not only provides a resource for investigating the unidentified functions of VRK1/VRK3, but also an insight into the regulatory roles of VRK1/VRK3 in biological processes. (PMID:28927264)

Cross-species orthologs

68 orthologs

Organism	Symbol	Gene ID
danio_rerio	vrk1	ENSDARG00000018006
mus_musculus	Vrk1	ENSMUSG00000021115
rattus_norvegicus	Vrk1	ENSRNOG00000005274
drosophila_melanogaster	ball	FBGN0027889
drosophila_melanogaster	CG9962	FBGN0031441
caenorhabditis_elegans		WBGENE00007049
caenorhabditis_elegans		WBGENE00007269
caenorhabditis_elegans		WBGENE00007305
caenorhabditis_elegans		WBGENE00007335
caenorhabditis_elegans		WBGENE00007448
caenorhabditis_elegans		WBGENE00007777
caenorhabditis_elegans		WBGENE00007791
caenorhabditis_elegans		WBGENE00008088
caenorhabditis_elegans		WBGENE00008423
caenorhabditis_elegans		WBGENE00008464
caenorhabditis_elegans	F10G8.2	WBGENE00008662
caenorhabditis_elegans		WBGENE00008883
caenorhabditis_elegans		WBGENE00009324
caenorhabditis_elegans		WBGENE00009402
caenorhabditis_elegans		WBGENE00010555
caenorhabditis_elegans		WBGENE00010692
caenorhabditis_elegans		WBGENE00010874
caenorhabditis_elegans		WBGENE00011283
caenorhabditis_elegans		WBGENE00012169
caenorhabditis_elegans		WBGENE00012637
caenorhabditis_elegans		WBGENE00012731
caenorhabditis_elegans		WBGENE00013868
caenorhabditis_elegans		WBGENE00014007
caenorhabditis_elegans		WBGENE00015893
caenorhabditis_elegans		WBGENE00016111
caenorhabditis_elegans	C34B2.3	WBGENE00016388
caenorhabditis_elegans		WBGENE00016513
caenorhabditis_elegans		WBGENE00016541
caenorhabditis_elegans		WBGENE00016673
caenorhabditis_elegans		WBGENE00016765
caenorhabditis_elegans	C55B7.10	WBGENE00016946
caenorhabditis_elegans		WBGENE00016963
caenorhabditis_elegans		WBGENE00017050
caenorhabditis_elegans		WBGENE00017714
caenorhabditis_elegans		WBGENE00017725
caenorhabditis_elegans		WBGENE00017803
caenorhabditis_elegans		WBGENE00017895
caenorhabditis_elegans	F33D11.7	WBGENE00018004
caenorhabditis_elegans		WBGENE00018122
caenorhabditis_elegans		WBGENE00018123
caenorhabditis_elegans		WBGENE00018202
caenorhabditis_elegans		WBGENE00018203
caenorhabditis_elegans		WBGENE00018745
caenorhabditis_elegans		WBGENE00018839
caenorhabditis_elegans		WBGENE00019086
caenorhabditis_elegans		WBGENE00019119
caenorhabditis_elegans		WBGENE00019459
caenorhabditis_elegans		WBGENE00019556
caenorhabditis_elegans		WBGENE00019561
caenorhabditis_elegans		WBGENE00019562
caenorhabditis_elegans		WBGENE00019642
caenorhabditis_elegans	kin-35	WBGENE00019769
caenorhabditis_elegans		WBGENE00020071
caenorhabditis_elegans		WBGENE00020072
caenorhabditis_elegans		WBGENE00020223
caenorhabditis_elegans		WBGENE00020580
caenorhabditis_elegans	W09C3.1	WBGENE00021109
caenorhabditis_elegans	Y47G6A.13	WBGENE00021639
caenorhabditis_elegans	Y65B4A.9	WBGENE00022032
caenorhabditis_elegans		WBGENE00022102
caenorhabditis_elegans	Y71F9AL.2	WBGENE00022108
caenorhabditis_elegans		WBGENE00022705
caenorhabditis_elegans		WBGENE00022707

Paralogs (12): VRK2 (ENSG00000028116), CDC7 (ENSG00000097046), VRK3 (ENSG00000105053), CSNK1A1 (ENSG00000113712), TTBK2 (ENSG00000128881), CSNK1G2 (ENSG00000133275), CSNK1D (ENSG00000141551), TTBK1 (ENSG00000146216), CSNK1G3 (ENSG00000151292), CSNK1G1 (ENSG00000169118), CSNK1A1L (ENSG00000180138), CSNK1E (ENSG00000213923)

Protein

Protein identifiers

Serine/threonine-protein kinase VRK1 — Q99986 (reviewed: Q99986)

Alternative names: Vaccinia-related kinase 1

All UniProt accessions (38): Q99986, A0A7P0T814, A0A7P0T824, A0A7P0T832, A0A7P0T833, A0A7P0T838, A0A7P0T8M0, A0A7P0T8N0, A0A7P0T8Z5, A0A7P0T925, A0A7P0T952, A0A7P0T977, A0A7P0T9B1, A0A7P0T9C6, A0A7P0T9E5, A0A7P0T9I1, A0A7P0T9T1, A0A7P0TA07, A0A7P0TA16, A0A7P0TA65, A0A7P0TAA6, A0A7P0TAI5, A0A7P0TAS8, A0A7P0TB08, A0A7P0TB15, A0A7P0TB37, A0A7P0TBB8, A0A7P0TBE4, A0A7P0TBI6, A0A7P0Z3Z7, A0A7P0Z445, A0A7P0Z462, A0A7P0Z4A4, A0A7P0Z4C8, A0A7P0Z4P9, H0YJ50, H0YJF7, H0YJJ9

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response. Controls chromatin organization and remodeling by mediating phosphorylation of histone H3 on ‘Thr-4’ and histone H2AX (H2aXT4ph). It also phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chromatin and histone acetyltransferase activity. Is involved in the regulation of cell cycle progression of neural progenitors, and is required for proper cortical neuronal migration. Is involved in neurite elongation and branching in motor neurons, and has an essential role in Cajal bodies assembly, acting through COIL phosphorylation and the control of coilin degradation. Involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, it is required to induce Golgi fragmentation. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm. Phosphorylates TP53BP1 and p53/TP53 on ‘Thr-18’, preventing the interaction between p53/TP53 and MDM2. Phosphorylates ATF2 which activates its transcriptional activity. Phosphorylates JUN.

Subunit / interactions. Interacts with HDAC1, KAT2B, SETDB1, KDM3A and KDM4A. Associates with the nucleosome through interactions with nucleosome DNA, histone H2A and histone H2B; the interaction with H2A and H2B is mediated by the nucleosome acidic patch, a cluster of negatively charged residues of H2A and H2B forming a cleft within the nucleosome core. (Microbial infection) Interacts with vaccinia protein B12; this interaction inhibits the repressive activity of the vaccinia virus B12 pseudokinase on viral replication factory formation.

Subcellular location. Nucleus. Cytoplasm. Cajal body.

Tissue specificity. Widely expressed. Highly expressed in fetal liver, testis and thymus.

Post-translational modifications. Autophosphorylated at various serine and threonine residues. Autophosphorylation does not impair its ability to phosphorylate p53/TP53. Phosphorylation by PLK3 leads to induction of Golgi fragmentation during mitosis.

Disease relevance. Pontocerebellar hypoplasia 1A (PCH1A) [MIM:607596] A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH1A is an autosomal recessive form characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and spinal cord anterior horn cells degeneration resembling infantile spinal muscular atrophy. Additional features include muscle hypotonia, congenital contractures and respiratory insufficiency that is evident at birth. The disease is caused by variants affecting the gene represented in this entry. Neuronopathy, distal hereditary motor, autosomal recessive 10 (HMNR10) [MIM:620542] A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. HMNR10 is a slowly progressive form characterized by distal muscle weakness and atrophy predominantly affecting the lower limbs, and resulting in gait abnormalities. Upper limb involvement is seen in some patients. HMNR10 has mostly juvenile or adult onset, although symptoms may manifest in infancy or childhood in some patients. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Active in presence of Mn(2+), Mg(2+) and Zn(2+), but is not functional with Ca(2+) or Cu(2+). Has a higher affinity for Mn(2+) than for Mg(2+). RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3.

Similarity. Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.

RefSeq proteins (3): NP_001397980, NP_001397982, NP_003375* (*=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
IPR050235	CK1_Ser-Thr_kinase-like	Family

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• 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 (77 total): strand 16, mutagenesis site 15, sequence variant 14, helix 14, modified residue 4, turn 4, region of interest 2, compositionally biased region 2, binding site 2, chain 1, domain 1, cross-link 1, active site 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
7M10	X-RAY DIFFRACTION	1.15
6BRU	X-RAY DIFFRACTION	1.8
6BU6	X-RAY DIFFRACTION	1.8
6BP0	X-RAY DIFFRACTION	1.9
6BTW	X-RAY DIFFRACTION	1.9
5UVF	X-RAY DIFFRACTION	2
6CNX	X-RAY DIFFRACTION	2
6VXU	X-RAY DIFFRACTION	2
9ZKG	X-RAY DIFFRACTION	2.06
6AC9	X-RAY DIFFRACTION	2.07
6CMM	X-RAY DIFFRACTION	2.1
6DD4	X-RAY DIFFRACTION	2.1
6CQH	X-RAY DIFFRACTION	2.15
6NPN	X-RAY DIFFRACTION	2.2
6CSW	X-RAY DIFFRACTION	2.25
8V42	X-RAY DIFFRACTION	2.3
3OP5	X-RAY DIFFRACTION	2.4
5UKF	X-RAY DIFFRACTION	2.4
6CFM	X-RAY DIFFRACTION	2.45
6VZH	X-RAY DIFFRACTION	2.55
7TAN	ELECTRON MICROSCOPY	3
8F8Y	X-RAY DIFFRACTION	3.06
2KTY	SOLUTION NMR
2KUL	SOLUTION NMR
2LAV	SOLUTION NMR
2RSV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99986-F1	85.37	0.75

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): 177 (proton acceptor)

Ligand- & substrate-binding residues (2): 43–51; 71

Post-translational modifications (5): 355, 376, 378, 71, 342

Mutagenesis-validated functional residues (15):

Position	Phenotype
14	does not abolish autophosphorylation.
102	does not abolish autophosphorylation.
125	does not abolish autophosphorylation.
150	does not abolish autophosphorylation.
158	does not abolish autophosphorylation.
179	does not affect phosphorylation at s-342.
179	loss of kinase activity. unable to phosphorylate coil, h3, h2ax, tp53, tp53bp1 and atf2.
239	does not abolish autophosphorylation.
305	does not abolish autophosphorylation.
312	does not abolish autophosphorylation.
342	abolishes phosphorylation by plk3 and induction of golgi fragmentation during mitosis. strongly reduced autophosphorylat
353	strongly reduced autophosphorylation.
355	does not abolish autophosphorylation.
387–393	abolishes interaction with nucleosome. decreased histone h3 phosphorylation.
390	does not abolish autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation

MSigDB gene sets: 420 (showing top): HORIUCHI_WTAP_TARGETS_DN, GOBP_MEMBRANE_DISASSEMBLY, GOLDRATH_IMMUNE_MEMORY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEUROGENESIS, GNF2_MCM5, GNF2_RRM1, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, SCHUHMACHER_MYC_TARGETS_UP, GNF2_ANP32B, GNF2_SMC4L1, GOBP_PROTEIN_LOCALIZATION_TO_CHROMATIN, GOBP_NUCLEUS_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME

GO Biological Process (13): chromatin remodeling (GO:0006338), protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), mitotic nuclear membrane disassembly (GO:0007077), signal transduction (GO:0007165), Cajal body organization (GO:0030576), neuron projection development (GO:0031175), protein autophosphorylation (GO:0046777), cell division (GO:0051301), Golgi disassembly (GO:0090166), positive regulation of protein localization to chromatin (GO:0120187), regulation of neuron migration (GO:2001222), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (14): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), kinase activity (GO:0016301), protein kinase binding (GO:0019901), nucleosomal DNA binding (GO:0031492), histone H3S10 kinase activity (GO:0035175), histone binding (GO:0042393), histone H3T3 kinase activity (GO:0072354), protein serine kinase activity (GO:0106310), histone H2AX kinase activity (GO:0141003), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi stack (GO:0005795), cytosol (GO:0005829), Cajal body (GO:0015030), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Mitotic Prophase	1
Nuclear Envelope (NE) Reassembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cellular process	2
protein kinase activity	2
protein serine/threonine kinase activity	2
histone H3 kinase activity	2
nuclear lumen	2
chromatin organization	1
phosphorylation	1
protein modification process	1
cellular response to stress	1
mitotic cell cycle	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
nuclear body organization	1
neuron development	1
plasma membrane bounded cell projection organization	1
protein phosphorylation	1
Golgi organization	1
Golgi inheritance	1
organelle disassembly	1
protein localization to chromatin	1
positive regulation of protein localization	1
regulation of protein localization to chromatin	1
neuron migration	1
regulation of cell migration	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
kinase binding	1
chromatin DNA binding	1

Protein interactions and networks

STRING

2476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VRK1	BDKRB1	P46663	852
VRK1	TSEN54	Q7Z6J9	776
VRK1	RARS2	Q5T160	775
VRK1	BANF1	O75531	742
VRK1	BANF2	Q9H503	742
VRK1	ANKLE2	Q86XL3	713
VRK1	CREB1	P16220	662
VRK1	MACROH2A1	O75367	583
VRK1	JUN	P05412	536
VRK1	TSEN2	Q8NCE0	532
VRK1	TSEN34	Q9BSV6	520
VRK1	EXOSC3	Q9NQT5	520
VRK1	LEMD3	Q9Y2U8	495
VRK1	EMD	P50402	491
VRK1	SMN1	Q16637	491

IntAct

207 interactions, top by confidence:

A	B	Type	Score
RAN	RCC1	psi-mi:“MI:0914”(association)	0.950
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
VRK1	TP53	psi-mi:“MI:0217”(phosphorylation reaction)	0.760
TP53	VRK1	psi-mi:“MI:0403”(colocalization)	0.760
TP53	VRK1	psi-mi:“MI:0915”(physical association)	0.760
VRK1	TP53	psi-mi:“MI:0915”(physical association)	0.760
	VRK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.730
	Tp53	psi-mi:“MI:0217”(phosphorylation reaction)	0.730
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VRK1	COIL	psi-mi:“MI:0217”(phosphorylation reaction)	0.680
VRK1	COIL	psi-mi:“MI:0915”(physical association)	0.680
VRK1	COIL	psi-mi:“MI:0403”(colocalization)	0.680
COIL	VRK1	psi-mi:“MI:0407”(direct interaction)	0.680
COIL	VRK1	psi-mi:“MI:0915”(physical association)	0.680
COIL	VRK1	psi-mi:“MI:0403”(colocalization)	0.680

BioGRID (339): VRK1 (Reconstituted Complex), VRK1 (Affinity Capture-MS), VRK1 (Affinity Capture-MS), RACGAP1 (Co-fractionation), RAN (Affinity Capture-Western), RCC1 (Affinity Capture-Western), COIL (Affinity Capture-Western), COIL (Co-fractionation), HIST3H3 (Affinity Capture-Western), VRK1 (Biochemical Activity), COIL (Biochemical Activity), VRK1 (Affinity Capture-Western), VRK1 (Proximity Label-MS), VRK1 (Proximity Label-MS), VRK1 (Affinity Capture-Western)

ESM2 similar proteins: A8XW88, B9VVJ6, O15726, O76324, P35507, P35508, P35509, P40235, P40236, P42168, P48729, P48730, P49185, P49674, P54367, P67827, P67828, P67829, P67962, P67963, P78368, P79996, P97633, Q06486, Q32PI1, Q4R9A9, Q556Y4, Q5BP74, Q5PRD4, Q5RC72, Q5ZLL1, Q62761, Q62762, Q62763, Q6P3K7, Q6P647, Q6QNL9, Q6QNM1, Q7RBX5, Q7T2E3

Diamond homologs: A0A7H0DNE9, A0A7H0DNF8, A8WU31, O23304, O57252, O57259, O74135, P16913, P20505, P21098, P24362, P33800, P81123, Q02720, Q19848, Q2YDN8, Q32PI1, Q4VSN1, Q54P47, Q7KRY6, Q7ZUS1, Q80X41, Q86Y07, Q8BN21, Q8IV63, Q8K3G5, Q91FD5, Q99986, Q9J509, Q9J523, O15726, P40235, P42168, P54367, Q39050, Q5XF24, Q6K9N1, Q6QNL9, Q6QNM1, Q7RBX5

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
VRK1	up-regulates	ATF2	phosphorylation
VRK1	up-regulates	JUN	phosphorylation
VRK1	down-regulates	BANF1	phosphorylation
VRK1	unknown	H3C1	phosphorylation
PLK3	up-regulates	VRK1	phosphorylation
VRK1	up-regulates	TP53BP1	phosphorylation
ANKLE2	down-regulates	VRK1
VRK1	unknown	“Histone H3”	phosphorylation
PRKCD	“down-regulates activity”	VRK1	phosphorylation
VRK1	“up-regulates activity”	H2AX	phosphorylation
VRK1	“up-regulates activity”	SOX2	phosphorylation
VRK1	“up-regulates quantity by stabilization”	COIL	phosphorylation
VRK1	“up-regulates activity”	AURKB	phosphorylation
VRK1	up-regulates	TP53	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 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
Nonhomologous End-Joining (NHEJ)	7	14.5×	7e-05
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	8	14.5×	2e-05
G2/M DNA damage checkpoint	9	13.4×	1e-05
DNA Damage/Telomere Stress Induced Senescence	6	12.1×	8e-04
Processing of DNA double-strand break ends	7	9.9×	7e-04
Condensation of Prophase Chromosomes	5	9.7×	8e-03
Meiotic recombination	6	9.6×	3e-03
Pre-NOTCH Transcription and Translation	6	9.1×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
DNA damage response, signal transduction by p53 class mediator	5	16.8×	3e-03
mitotic spindle organization	6	15.2×	1e-03
double-strand break repair	7	13.3×	1e-03
DNA damage response	10	5.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	39
Uncertain significance	178
Likely benign	271
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067636	NM_003384.3(VRK1):c.1096_1097insTGAAGCA (p.Lys366fs)	Pathogenic
1071258	NM_003384.3(VRK1):c.110G>A (p.Trp37Ter)	Pathogenic
1076855	NM_003384.3(VRK1):c.387dup (p.Ile130fs)	Pathogenic
1383284	NM_003384.3(VRK1):c.783G>A (p.Trp261Ter)	Pathogenic
1399359	NM_003384.3(VRK1):c.542_543insGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGGCCTC (p.Ser181_Asn182insArgGlyGlySerArgLeuTer)	Pathogenic
1403721	NM_003384.3(VRK1):c.897del (p.Ile299fs)	Pathogenic
1408344	NM_003384.3(VRK1):c.913dup (p.Thr305fs)	Pathogenic
1431709	NM_003384.3(VRK1):c.733G>T (p.Glu245Ter)	Pathogenic
1453030	NM_003384.3(VRK1):c.179_180del (p.Glu60fs)	Pathogenic
1453248	NM_003384.3(VRK1):c.1133_1136del (p.Thr378fs)	Pathogenic
1455719	NC_000014.8:g.(?97326874)(97327092_?)del	Pathogenic
1456740	NM_003384.3(VRK1):c.652A>T (p.Lys218Ter)	Pathogenic
1457447	NC_000014.8:g.(?97299809)(97327092_?)del	Pathogenic
1459674	NM_003384.3(VRK1):c.103_104del (p.Lys35fs)	Pathogenic
1460187	NC_000014.8:g.(?97319158)(97322933_?)del	Pathogenic
2003519	NM_003384.3(VRK1):c.1061dup (p.Thr355fs)	Pathogenic
2036712	NM_003384.3(VRK1):c.950_951dup (p.Glu318fs)	Pathogenic
2039561	NM_003384.3(VRK1):c.500del (p.Tyr167fs)	Pathogenic
2062005	NM_003384.3(VRK1):c.1149del (p.Ile384fs)	Pathogenic
2101376	NM_003384.3(VRK1):c.22C>T (p.Gln8Ter)	Pathogenic
2108163	NM_003384.3(VRK1):c.159_160insCATATATCTT (p.Ala54fs)	Pathogenic
2150009	NM_003384.3(VRK1):c.160+1del	Pathogenic
2167963	NM_003384.3(VRK1):c.633_636del (p.Lys211fs)	Pathogenic
2428131	NM_003384.3(VRK1):c.105_108del (p.Lys35fs)	Pathogenic
2541929	NM_003384.3(VRK1):c.464T>A (p.Leu155Ter)	Pathogenic
2699211	NM_003384.3(VRK1):c.542C>G (p.Ser181Ter)	Pathogenic
2717633	NM_003384.3(VRK1):c.881del (p.Asn294fs)	Pathogenic
2724908	NM_003384.3(VRK1):c.31A>T (p.Arg11Ter)	Pathogenic
2739534	NM_003384.3(VRK1):c.280_284del (p.Glu94fs)	Pathogenic
2754805	NM_003384.3(VRK1):c.854del (p.Ser284_Leu285insTer)	Pathogenic

SpliceAI

2446 predictions. Top by Δscore:

Variant	Effect	Δscore
14:96797406:G:GT	donor_gain	1.0000
14:96797406:G:T	donor_gain	1.0000
14:96818110:T:G	donor_gain	1.0000
14:96833459:T:G	acceptor_gain	1.0000
14:96833464:TAGT:T	acceptor_loss	1.0000
14:96833465:A:AG	acceptor_gain	1.0000
14:96833465:AGT:A	acceptor_gain	1.0000
14:96833466:G:GA	acceptor_gain	1.0000
14:96833466:GT:G	acceptor_gain	1.0000
14:96833466:GTG:G	acceptor_gain	1.0000
14:96833466:GTGA:G	acceptor_gain	1.0000
14:96833466:GTGAA:G	acceptor_gain	1.0000
14:96833583:A:T	donor_gain	1.0000
14:96833608:G:GT	donor_gain	1.0000
14:96833627:TCTTG:T	donor_gain	1.0000
14:96833628:CTTG:C	donor_gain	1.0000
14:96833632:G:GA	donor_loss	1.0000
14:96833632:G:GG	donor_gain	1.0000
14:96833633:T:TC	donor_loss	1.0000
14:96837815:GTG:G	donor_gain	1.0000
14:96846090:TTAA:T	acceptor_loss	1.0000
14:96846091:TAAGG:T	acceptor_loss	1.0000
14:96846092:AAG:A	acceptor_gain	1.0000
14:96846093:A:G	acceptor_gain	1.0000
14:96846093:AGG:A	acceptor_loss	1.0000
14:96846160:GCAAA:G	donor_gain	1.0000
14:96846165:G:GG	donor_gain	1.0000
14:96846177:G:GG	donor_gain	1.0000
14:96847255:A:AG	acceptor_gain	1.0000
14:96847256:G:GG	acceptor_gain	1.0000

AlphaMissense

2612 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:96856201:T:A	W261R	1.000
14:96856201:T:C	W261R	1.000
14:96833613:T:C	F48L	0.999
14:96833615:T:A	F48L	0.999
14:96833615:T:G	F48L	0.999
14:96837814:A:C	K71N	0.999
14:96837814:A:T	K71N	0.999
14:96855237:A:C	D197A	0.999
14:96855237:A:T	D197V	0.999
14:96855238:T:A	D197E	0.999
14:96855238:T:G	D197E	0.999
14:96855332:A:C	S229R	0.999
14:96855334:C:A	S229R	0.999
14:96855334:C:G	S229R	0.999
14:96853120:A:C	D177A	0.998
14:96853120:A:T	D177V	0.998
14:96853121:T:A	D177E	0.998
14:96853121:T:G	D177E	0.998
14:96853127:G:C	K179N	0.998
14:96853127:G:T	K179N	0.998
14:96853138:T:C	L183P	0.998
14:96855236:G:C	D197H	0.998
14:96855315:G:A	G223D	0.998
14:96856180:T:A	W254R	0.998
14:96856180:T:C	W254R	0.998
14:96856203:G:C	W261C	0.998
14:96856203:G:T	W261C	0.998
14:96856245:A:C	K275N	0.998
14:96856245:A:T	K275N	0.998
14:96853084:T:C	L165P	0.997

dbSNP variants (sampled 300 via entrez): RS1000022894 (14:96869960 T>C), RS1000045627 (14:96817642 C>T), RS1000238854 (14:96800504 T>C), RS1000255980 (14:96836026 T>G), RS1000265128 (14:96851328 A>G), RS1000274378 (14:96819543 G>C), RS1000334748 (14:96806813 CCCCT>C,CCCCTCCCT), RS1000351125 (14:96805194 A>G,T), RS1000391995 (14:96848982 T>C), RS1000428828 (14:96812764 A>G), RS1000437883 (14:96798053 C>T), RS1000461820 (14:96849312 T>C), RS1000519179 (14:96839057 A>C,T), RS1000561220 (14:96810989 G>A), RS1000636186 (14:96842187 A>G,T)

Disease associations

OMIM: gene MIM:602168 | disease phenotypes: MIM:607596, MIM:620542, MIM:253300, MIM:604320, MIM:610093, MIM:614678

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia type 1A	Strong	Autosomal recessive
neuronopathy, distal hereditary motor, autosomal recessive 10	Strong	Autosomal recessive
pontocerebellar hypoplasia type 1	Supportive	Autosomal recessive
microcephaly-complex motor and sensory axonal neuropathy syndrome	Supportive	Autosomal recessive

Mondo (13): pontocerebellar hypoplasia type 1A (MONDO:0011866), distal hereditary motor neuropathy (MONDO:0018894), neuronopathy, distal hereditary motor, autosomal recessive 10 (MONDO:0957876), spinal muscular atrophy (MONDO:0001516), amyotrophic lateral sclerosis (MONDO:0004976), neuronopathy, distal hereditary motor, autosomal recessive (MONDO:0015363), pontocerebellar hypoplasia type 1 (MONDO:0016396), isolated microphthalmia 2 (MONDO:0012409), pontocerebellar hypoplasia (MONDO:0020135), juvenile amyotrophic lateral sclerosis (MONDO:0017593), pontocerebellar hypoplasia type 1B (MONDO:0013853), hereditary breast ovarian cancer syndrome (MONDO:0003582), microcephaly-complex motor and sensory axonal neuropathy syndrome (MONDO:0018507)

Orphanet (10): Pontocerebellar hypoplasia type 1 (Orphanet:2254), Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Distal hereditary motor neuropathy (Orphanet:53739), Autosomal recessive distal hereditary motor neuropathy (Orphanet:140468), Amyotrophic lateral sclerosis (Orphanet:803), Isolated microphthalmia-anophthalmia-coloboma (Orphanet:2542), Non-syndromic pontocerebellar hypoplasia (Orphanet:98523), Juvenile amyotrophic lateral sclerosis (Orphanet:300605), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Microcephaly-complex motor and sensory axonal neuropathy syndrome (Orphanet:423894)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000486	Strabismus
HP:0000529	Progressive visual loss
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001308	Tongue fasciculations
HP:0001321	Cerebellar hypoplasia
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001508	Failure to thrive
HP:0001760	Abnormal foot morphology
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001765	Hammertoe
HP:0002015	Dysphagia
HP:0002033	Poor suck
HP:0002070	Limb ataxia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001059_9	Neutrophil count	8.000000e-06
GCST002386_10	Cognitive function	8.000000e-06
GCST002440_4	Staphylococcus aureus infection	8.000000e-07
GCST002938_27	Copper levels	4.000000e-06
GCST003542_95	Night sleep phenotypes	8.000000e-06
GCST004350_20	Bone ultrasound measurement (velocity of sound)	3.000000e-07
GCST005351_4	Carboplatin disposition in epthelial ovarian cancer	6.000000e-06
GCST009391_2042	Metabolite levels	9.000000e-06
GCST010516_6	Fractures (paediatric)	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0003925	cognition
EFO:0004514	bone quantitative ultrasound measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D009134	Muscular Atrophy, Spinal	C10.228.854.468; C10.574.562.500; C10.668.467.500
C566446	Microphthalmia, Isolated 2 (supp.)
C580383	Pontocerebellar Hypoplasia (supp.)
C548069	Pontocerebellar Hypoplasia Type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293199 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Vaccina related kinase (VRK) family

ChEMBL bioactivities

46 potent at pChembl≥5 of 46 total, top 46 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.87	Ki	13.6	nM	CHEMBL5561272
7.75	Ki	17.9	nM	CHEMBL5557609
7.66	Ki	21.8	nM	CHEMBL5557379
7.64	Ki	23.1	nM	CHEMBL5564158
7.58	Ki	26.5	nM	CHEMBL5566532
7.58	Ki	26.1	nM	CHEMBL5557355
7.58	Ki	26.1	nM	CHEMBL5557387
7.51	Ki	31	nM	CHEMBL5557932
7.50	Ki	31.5	nM	CHEMBL5532198
7.50	Ki	31.7	nM	CHEMBL5523509
7.48	IC50	33	nM	CHEMBL573107
7.47	Ki	33.8	nM	CHEMBL5542657
7.45	Ki	35.2	nM	CHEMBL5559444
7.43	Ki	36.7	nM	CHEMBL5555299
7.43	Ki	36.9	nM	CHEMBL5558036
7.42	Ki	37.9	nM	CHEMBL5557062
7.30	Ki	50	nM	CHEMBL5542121
7.25	Ki	56.1	nM	CHEMBL573107
7.21	Ki	62.2	nM	CHEMBL5557286
7.18	Ki	66.5	nM	CHEMBL5549880
7.18	Ki	66.2	nM	CHEMBL5564373
7.14	Ki	72.6	nM	CHEMBL5562568
7.09	Ki	80.9	nM	CHEMBL5557942
7.06	Ki	87.3	nM	CHEMBL5542207
7.03	Ki	94	nM	CHEMBL5568610
7.03	Ki	94.2	nM	CHEMBL5558898
7.00	Ki	100.7	nM	CHEMBL3604889
6.98	Ki	104.7	nM	CHEMBL5565622
6.95	IC50	112.4	nM	CHEMBL6170056
6.92	Ki	121.1	nM	CHEMBL5555994
6.90	Ki	126.8	nM	CHEMBL5532547
6.89	Ki	128.8	nM	CHEMBL5561979
6.89	Ki	128.2	nM	CHEMBL5563756
6.87	Ki	134.6	nM	CHEMBL5561159
6.82	IC50	150	nM	CHEMBL4435359
6.74	Ki	183.2	nM	CHEMBL5560770
6.74	Ki	181.6	nM	CHEMBL5559784
6.72	Kd	190	nM	CHEMBL4435359
6.71	Ki	194.1	nM	CHEMBL5562037
6.67	Ki	213.8	nM	CHEMBL5557685
6.58	IC50	260	nM	CHEMBL4436323
6.17	IC50	674	nM	CHEMBL4452098
6.13	IC50	743	nM	BISINDOLYLMALEIMIDE IX
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n

PubChem BioAssay actives

42 with measured affinity, of 283 total; 40 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
(7R)-2-[(3-amino-1H-indazol-6-yl)amino]-7-methyl-5,8-bis(prop-2-ynyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0136	uM
(7R)-7-methyl-2-[(3-oxo-1,2-dihydroindazol-6-yl)amino]-5,8-bis(prop-2-ynyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0179	uM
(7S)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-5-[(3-methyl-1,2-oxazol-5-yl)methyl]-8-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0218	uM
(7R)-8-(cyclopropylmethyl)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-5-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0231	uM
2-[(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-6-oxo-8-prop-2-ynyl-7H-pteridin-5-yl]acetonitrile	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0261	uM
2-[(7S)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-6-oxo-8-prop-2-ynyl-7H-pteridin-5-yl]acetonitrile	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0261	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-5-[(3-methyl-1,2-oxazol-5-yl)methyl]-8-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0265	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-8-propyl-5-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0310	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-8-(3-methylbutyl)-5-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0315	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-8-prop-2-enyl-5-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0317	uM
2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-(3-methylbutyl)-7H-pteridin-6-one	1511461: Inhibition of full length wild-type VRK1 (unknown origin) expressed in insect cells using ULight-Histone 3-Thr3 peptide as substrate incubated for 30 mins followed by substrate addition further incubated for 75 mins by fluorescence based assay	ic50	0.0330	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-5,8-bis(prop-2-ynyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0338	uM
(7S)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-5-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0352	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-8-ethyl-7-methyl-5-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0367	uM
(7S)-7-methyl-2-[(3-oxo-1,2-dihydroindazol-6-yl)amino]-5,8-bis(prop-2-ynyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0369	uM
(7S)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-5-[(3-methyl-1,2-oxazol-5-yl)methyl]-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0379	uM
2-[(7S)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-6-oxo-7H-pteridin-5-yl]acetonitrile	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0500	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-5-ethyl-7-methyl-8-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0622	uM
2-[(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-6-oxo-7H-pteridin-5-yl]acetonitrile	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0662	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-propyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0665	uM
(7R)-2-[(2-amino-4-methyl-1,3-benzothiazol-6-yl)amino]-7-methyl-5,8-bis(prop-2-ynyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0726	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-5-(1,2-oxazol-5-ylmethyl)-8-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0809	uM
[3-fluoro-4-[[(7R)-7-methyl-6-oxo-5,8-bis(prop-2-ynyl)-7H-pteridin-2-yl]amino]phenyl]boronic acid	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0873	uM
[4-[[(7R)-7-methyl-6-oxo-5,8-bis(prop-2-ynyl)-7H-pteridin-2-yl]amino]phenyl]boronic acid	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0940	uM
(7S)-2-(3,5-difluoro-4-hydroxyanilino)-7-methyl-5,8-bis(prop-2-ynyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.0942	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-(3-methylbutyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1007	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-5-(3-hydroxy-3-methylbutyl)-7-methyl-8-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1047	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-5-(3-methylbut-2-enyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1211	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-5-[(3-methyl-1,2-oxazol-5-yl)methyl]-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1268	uM
(7R)-5-butyl-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1282	uM
(7R)-8-benzyl-2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1288	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1346	uM
4-[5-(3,5-difluoro-4-hydroxyphenyl)-6-methyl-3-pyridinyl]-2,6-difluorophenol	1511461: Inhibition of full length wild-type VRK1 (unknown origin) expressed in insect cells using ULight-Histone 3-Thr3 peptide as substrate incubated for 30 mins followed by substrate addition further incubated for 75 mins by fluorescence based assay	ic50	0.1500	uM
(7R)-2-(3-chloro-4-hydroxyanilino)-7-methyl-5,8-bis(prop-2-ynyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1816	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-5-(3-methylbutyl)-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1832	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-5-prop-2-ynyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.1941	uM
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-prop-2-enyl-7H-pteridin-6-one	2077261: Inhibition of human VRK1 (3 to 364 residues) expressed in Escherichia coli BL21 (DE3)-R3 cells assessed as inhibition constant using human histone H3 peptide as substrate preincubated for 30 mins followed by substrate and ATP addition incubated for 60 mins by Cheng-Prusoff equation based TR-FRET assay	ki	0.2138	uM
4-[6-amino-5-(3,5-difluoro-4-hydroxyphenyl)-3-pyridinyl]-2,6-difluorophenol	1511461: Inhibition of full length wild-type VRK1 (unknown origin) expressed in insect cells using ULight-Histone 3-Thr3 peptide as substrate incubated for 30 mins followed by substrate addition further incubated for 75 mins by fluorescence based assay	ic50	0.2600	uM
4-[2-amino-5-(1,3-benzothiazol-6-yl)-3-pyridinyl]-2,6-difluorophenol	1511461: Inhibition of full length wild-type VRK1 (unknown origin) expressed in insect cells using ULight-Histone 3-Thr3 peptide as substrate incubated for 30 mins followed by substrate addition further incubated for 75 mins by fluorescence based assay	ic50	0.6740	uM
3-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]propyl carbamimidothioate	1531925: Inhibition of human VRK1 using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate by [gamma-33P]-ATP assay	ic50	0.7430	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	3
Benzo(a)pyrene	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
afuresertib	decreases expression	1
FR900359	increases phosphorylation	1
moringin	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	affects expression, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
picoxystrobin	increases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1

ChEMBL screening assays

74 unique, capped per target: 74 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1043841	Binding	Residual activity of VRK1 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3L9	Abcam HEK293T VRK1 KO	Transformed cell line	Female
CVCL_TX72	HAP1 VRK1 (-) 1	Cancer cell line	Male
CVCL_TX73	HAP1 VRK1 (-) 2	Cancer cell line	Male
CVCL_TX74	HAP1 VRK1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT05232929	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA)
NCT05522361	PHASE4	ACTIVE_NOT_RECRUITING	Risdiplam in Patients With Spinal Muscular Atrophy Previously Treated With Nusinersen
NCT07448610	PHASE4	NOT_YET_RECRUITING	ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT01671384	PHASE3	UNKNOWN	Valproate and Levocarnitine in Children With Spinal Muscular Atrophy
NCT02193074	PHASE3	TERMINATED	A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy
NCT02292537	PHASE3	COMPLETED	A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Participants With Later-onset Spinal Muscular Atrophy (SMA)
NCT02594124	PHASE3	COMPLETED	A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
NCT03505099	PHASE3	COMPLETED	Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2
NCT03837184	PHASE3	COMPLETED	Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
NCT04042025	PHASE3	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
NCT04851873	PHASE3	COMPLETED	Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
NCT05067790	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND)
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05335876	PHASE3	RECRUITING	Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05386680	PHASE3	COMPLETED	Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT07265232	PHASE3	RECRUITING	Real World Clinical Effectiveness & Safety of Vesemnogene Lantuparvovec for Spinal Muscular Atrophy (SMA) in Low-middle Income Countries (LMIC).
NCT07444476	PHASE3	RECRUITING	A Study to Learn About Salanersen’s (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years With Spinal Muscular Atrophy (SMA) Who Are Either New to SMA Treatment or Were Previously Treated With Risdiplam
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
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