VRK3

Summary

VRK3 (VRK serine/threonine kinase 3, HGNC:18996) is a protein-coding gene on chromosome 19q13.33, encoding Serine/threonine-protein kinase VRK3 (Q8IV63). Plays a role in the regulation of the cell cycle by phosphorylating the nuclear envelope protein barrier-to-autointegration factor/BAF that is required for disassembly and reassembly, respectively, of the nuclear envelope during mitosis.

This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. In both human and mouse, this gene has substitutions at several residues within the ATP binding motifs that in other kinases have been shown to be required for catalysis. In vitro assays indicate the protein lacks phosphorylation activity. The protein, however, likely retains its substrate binding capability. This gene is widely expressed in human tissues and its protein localizes to the nucleus. Alternative splicing results in multiple transcripts encoding different isoforms.

Source: NCBI Gene 51231 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_016440

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18996
Approved symbol	VRK3
Name	VRK serine/threonine kinase 3
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105053
Ensembl biotype	protein_coding
OMIM	619771
Entrez	51231

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 28 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000316763, ENST00000377011, ENST00000424804, ENST00000593912, ENST00000593919, ENST00000594090, ENST00000594092, ENST00000594104, ENST00000594948, ENST00000596121, ENST00000596445, ENST00000596814, ENST00000597215, ENST00000598553, ENST00000599138, ENST00000599342, ENST00000599538, ENST00000600031, ENST00000600137, ENST00000600259, ENST00000600284, ENST00000601324, ENST00000601341, ENST00000601849, ENST00000601912, ENST00000602029, ENST00000901183, ENST00000901184, ENST00000901185, ENST00000901186, ENST00000901187, ENST00000901188, ENST00000936082, ENST00000936083, ENST00000936084, ENST00000936085, ENST00000945336, ENST00000945337, ENST00000945338, ENST00000945339

RefSeq mRNA: 3 — MANE Select: NM_016440 NM_001025778, NM_001308420, NM_016440

CCDS: CCDS12791, CCDS33076, CCDS77334

Canonical transcript exons

ENST00000316763 — 15 exons

Exon	Start	End
ENSE00001365058	50020585	50020647
ENSE00001365472	49976468	49976784
ENSE00002215620	49979083	49979242
ENSE00003160342	50025267	50025372
ENSE00003465707	49997504	49997570
ENSE00003521877	49989639	49989771
ENSE00003540871	50016024	50016163
ENSE00003542709	50009236	50009385
ENSE00003556855	49992860	49992952
ENSE00003563003	49995191	49995275
ENSE00003572928	50000790	50000854
ENSE00003593789	49994814	49994919
ENSE00003627134	49980955	49981013
ENSE00003651113	49988372	49988492
ENSE00003784566	50007569	50007826

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8161 / max 228.2490, expressed in 1806 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182131	16.0800	1805
182132	0.4361	180
182133	0.1400	18
182135	0.0961	41
182136	0.0303	11
182130	0.0208	7
182134	0.0129	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.10	gold quality
right testis	UBERON:0004534	98.72	gold quality
left testis	UBERON:0004533	98.63	gold quality
male germ cell	CL:0000015	98.54	gold quality
testis	UBERON:0000473	96.42	gold quality
right uterine tube	UBERON:0001302	95.36	gold quality
granulocyte	CL:0000094	95.12	gold quality
adult organism	UBERON:0007023	93.72	gold quality
cerebellar hemisphere	UBERON:0002245	93.59	gold quality
cerebellar cortex	UBERON:0002129	93.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.40	gold quality
blood	UBERON:0000178	93.32	gold quality
mucosa of transverse colon	UBERON:0004991	92.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.79	gold quality
rectum	UBERON:0001052	92.75	gold quality
cerebellum	UBERON:0002037	92.31	gold quality
epithelium of bronchus	UBERON:0002031	92.20	gold quality
monocyte	CL:0000576	92.13	gold quality
bronchus	UBERON:0002185	92.06	gold quality
leukocyte	CL:0000738	92.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.95	gold quality
right lobe of liver	UBERON:0001114	91.93	gold quality
mononuclear cell	CL:0000842	91.87	gold quality
gall bladder	UBERON:0002110	91.85	gold quality
spinal cord	UBERON:0002240	91.72	gold quality
small intestine	UBERON:0002108	91.67	gold quality
ventricular zone	UBERON:0003053	91.62	gold quality
colonic epithelium	UBERON:0000397	91.52	gold quality
right adrenal gland	UBERON:0001233	91.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	19.02
E-ANND-3	yes	8.68
E-MTAB-6379	no	121.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting VRK3, 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-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-937-5P	97.43	68.39	667

Literature-anchored findings (GeneRIF, showing 8)

• 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)
• These data suggest that VRK3-mediated phosphorylation of BAF may facilitate DNA replication or gene expression by facilitating the dissociation of nuclear envelope proteins and chromatin during interphase. (PMID:25899223)
• Stress-induced nuclear translocation of CDK5 suppresses neuronal death by downregulating ERK activation via VRK3 phosphorylation (PMID:27346674)
• Nuclear HSP70 leads to enhancement of vaccinia H1-related phosphatase (VHR) activity via protein-protein interaction rather than its molecular chaperone activity, thereby suppressing excessive ERK activation. Downregulation of either VRK3 or HSP70 rendered cells vulnerable to glutamate-induced apoptosis. (PMID:27941812)
• Finally, downregulation of hvrk3 using siRNA reduced the amplitude and lengthened the period of the cellular bioluminescence rhythm. Taken together, these data suggest that VRK3 plays a role in setting the amplitude and period length of circadian rhythms in mammalian cells. (PMID:28412365)
• 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)
• VRK3 is an interesting and promising target in Diffuse intrinsic pontine glioma. (PMID:31324890)
• RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3. (PMID:33067254)

Cross-species orthologs

68 orthologs

Organism	Symbol	Gene ID
danio_rerio	vrk3	ENSDARG00000036056
mus_musculus	Vrk3	ENSMUSG00000002205
rattus_norvegicus	Vrk3	ENSRNOG00000026517
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), VRK1 (ENSG00000100749), 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 VRK3 — Q8IV63 (reviewed: Q8IV63)

Alternative names: Vaccinia-related kinase 3

All UniProt accessions (12): Q8IV63, M0QX88, M0QXD7, M0QXV1, M0QYA8, M0QYG0, M0QZ79, M0R025, M0R073, M0R164, M0R200, M0R3H2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of the cell cycle by phosphorylating the nuclear envelope protein barrier-to-autointegration factor/BAF that is required for disassembly and reassembly, respectively, of the nuclear envelope during mitosis. Under normal physiological conditions, negatively regulates ERK activity along with VHR/DUSP3 phosphatase in the nucleus, causing timely and transient action of ERK. Stress conditions activate CDK5 which phosphorylates VRK3 to increase VHR phosphatase activity and suppress prolonged ERK activation that causes cell death. For example, upon glutamate induction, promotes nuclear localization of HSP70/HSPA1A to inhibit ERK activation via VHR/DUSP3 phosphatase.

Subunit / interactions. Interacts with DUSP3. Interacts with RAN. Interacts with HSP70/HSPA1A.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Phosphorylated at Ser-108 by CDK5; leading to protection of the cell against H2O2-induced apoptosis. Ubiquitinated by RNF144A.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IV63-1	1	yes
Q8IV63-2	2
Q8IV63-3	3

RefSeq proteins (3): NP_001020949, NP_001295349, NP_057524* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR026870	Zinc_ribbon_dom	Domain
IPR050235	CK1_Ser-Thr_kinase-like	Family

Pfam: PF00069, PF13240

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (56 total): helix 14, sequence variant 10, modified residue 9, strand 8, splice variant 3, compositionally biased region 3, mutagenesis site 2, turn 2, chain 1, domain 1, region of interest 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2JII	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV63-F1	80.57	0.65

Functional residue map

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

Post-translational modifications (9): 82, 83, 90, 108, 115, 122, 54, 55, 59

Mutagenesis-validated functional residues (2):

Position	Phenotype
108	unable to be phosphorylated by cdk5.
203	complete loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-202670	ERKs are inactivated

MSigDB gene sets: 178 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, TGCGCANK_UNKNOWN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, REACTOME_ERK_MAPK_TARGETS, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (5): DNA damage response (GO:0006974), signal transduction (GO:0007165), skeletal muscle tissue development (GO:0007519), negative regulation of ERK1 and ERK2 cascade (GO:0070373), protein phosphorylation (GO:0006468)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), protein phosphatase binding (GO:0019903), protein phosphatase activator activity (GO:0072542), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ERK/MAPK targets	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
striated muscle tissue development	1
skeletal muscle organ development	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
phosphorylation	1
protein modification process	1
protein kinase activity	1
protein serine/threonine kinase activity	1
cyclin-dependent protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
phosphatase binding	1
phosphoprotein phosphatase activity	1
phosphatase activator activity	1
protein phosphatase regulator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VRK3	DUSP3	P51452	795
VRK3	BANF2	Q9H503	544
VRK3	STRADA	Q7RTN6	502
VRK3	EVI5	O60447	488
VRK3	MAD1L1	Q9Y6D9	482
VRK3	BANF1	O75531	470
VRK3	KSR1	Q8IVT5	465
VRK3	DUSP6	Q16828	455
VRK3	MT3	P25713	445
VRK3	SACK1B	Q5T0W9	419
VRK3	F5H6H0	F5H6H0	417
VRK3	SACK1H	Q6ZRV2	407
VRK3	TRIB1	Q96RU8	403
VRK3	ZNF621	Q6ZSS3	402
VRK3	NUCLEOLIN	P19338	401

IntAct

44 interactions, top by confidence:

A	B	Type	Score
MAX	MYC	psi-mi:“MI:0914”(association)	0.980
C16orf87	CDC27	psi-mi:“MI:0914”(association)	0.640
VRK1	RAN	psi-mi:“MI:0914”(association)	0.600
VRK3	USP54	psi-mi:“MI:0915”(physical association)	0.560
USP54	DYRK1A	psi-mi:“MI:0914”(association)	0.550
SP4	PTPRA	psi-mi:“MI:0914”(association)	0.530
ZNF524	C1QBP	psi-mi:“MI:0914”(association)	0.530
HMGA1	MACROH2A1	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
VRK3	MAX	psi-mi:“MI:0915”(physical association)	0.500
VRK3	RAN	psi-mi:“MI:0915”(physical association)	0.400
VRK3	RCBTB2	psi-mi:“MI:0915”(physical association)	0.400
VRK3	TSG101	psi-mi:“MI:0915”(physical association)	0.370
CSNK2B	VRK3	psi-mi:“MI:0915”(physical association)	0.370
PLK1	VRK3	psi-mi:“MI:0915”(physical association)	0.370
Cbx1		psi-mi:“MI:0914”(association)	0.350
FOXD3	MYL12B	psi-mi:“MI:0914”(association)	0.350
FOXP1	MYL12B	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
ORF73	ECI2	psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
TCF7L2	LOC401309	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TXNDC5	SPTB	psi-mi:“MI:0914”(association)	0.350
NR2E1	DCAF6	psi-mi:“MI:0914”(association)	0.350
VRK3	PSME3	psi-mi:“MI:0914”(association)	0.350
SRF	GPC4	psi-mi:“MI:0914”(association)	0.350
	BANF1	psi-mi:“MI:0914”(association)	0.350
HMGA2	KPNA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (168): VRK3 (Reconstituted Complex), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), TWF2 (Affinity Capture-MS), VRK3 (Biochemical Activity)

ESM2 similar proteins: A4PES0, A4QNA8, D2HHP1, D2HNY3, D4A7V9, E1BTE1, E2RSS3, E7FDW8, O57473, P0C1S8, P47817, P61800, Q14258, Q2YDN8, Q5EAN7, Q5R5X9, Q5XIX3, Q60953, Q66JT0, Q69ZT1, Q6DFE0, Q70CQ4, Q7TPQ3, Q7ZU92, Q80X41, Q86Y07, Q8BK58, Q8BN21, Q8BZ20, Q8IV63, Q8IYR2, Q8K3G5, Q8K4J0, Q8K4T3, Q91VL8, Q92918, Q96MI9, Q99MV5, Q9BVS5, Q9BY84

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, P24719, Q54RZ7, Q7TNJ7, Q852L0, Q8RX66, Q91VB2, Q96NX5, Q9SND6, A7E3X2, A8X4H1

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
VRK3	“down-regulates activity”	BANF1	phosphorylation
CDK5	“up-regulates activity”	VRK3	phosphorylation
CDK5/CDK5R1	“up-regulates activity”	VRK3	phosphorylation
VRK3	“up-regulates activity”	DUSP3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2535 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49979140:AGAT:A	donor_gain	1.0000
19:49988370:A:AC	donor_gain	1.0000
19:49988371:C:CC	donor_gain	1.0000
19:49988371:CTT:C	donor_gain	1.0000
19:49988373:T:TA	donor_gain	1.0000
19:49989633:TCGTA:T	donor_loss	1.0000
19:49989634:CGTAC:C	donor_loss	1.0000
19:49989635:GTAC:G	donor_loss	1.0000
19:49989636:TACCG:T	donor_loss	1.0000
19:49989637:A:AC	donor_gain	1.0000
19:49989637:A:C	donor_loss	1.0000
19:49989638:C:CC	donor_gain	1.0000
19:49989638:C:G	donor_loss	1.0000
19:49989638:CCG:C	donor_gain	1.0000
19:49989642:ATC:A	donor_gain	1.0000
19:49989644:C:A	donor_gain	1.0000
19:49989673:AAGGT:A	donor_gain	1.0000
19:49989769:CAC:C	acceptor_gain	1.0000
19:49992855:CTTA:C	donor_loss	1.0000
19:49992857:TA:T	donor_loss	1.0000
19:49992859:CCTGA:C	donor_gain	1.0000
19:49992948:TCCAG:T	acceptor_gain	1.0000
19:49992949:CCAG:C	acceptor_gain	1.0000
19:49992949:CCAGC:C	acceptor_gain	1.0000
19:49992950:CAG:C	acceptor_gain	1.0000
19:49992950:CAGC:C	acceptor_gain	1.0000
19:49992951:A:T	acceptor_gain	1.0000
19:49992952:GCTG:G	acceptor_loss	1.0000
19:49992953:C:CC	acceptor_gain	1.0000
19:49995185:GCTCA:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000032734 (19:50010128 C>T), RS1000053675 (19:50014214 C>G,T), RS1000141066 (19:49978776 A>G), RS1000165731 (19:50023278 C>G,T), RS1000245914 (19:50005713 C>T), RS1000388106 (19:49985850 G>A), RS1000422840 (19:49985567 C>A,T), RS1000455597 (19:49990608 A>C), RS1000468055 (19:50010509 C>T), RS1000469227 (19:50013060 G>A,T), RS1000498962 (19:49999452 G>A,C), RS1000604670 (19:50012938 C>T), RS1000636166 (19:49990438 G>A,C,T), RS1000656938 (19:49976833 C>A,T), RS1000673206 (19:49987024 C>T)

Disease associations

OMIM: gene MIM:619771 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011696_4	Alzheimer’s disease	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3430761 (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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	increases methylation	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
afimoxifene	decreases response to substance	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
jinfukang	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases methylation	1
Zinc	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3430847	Binding	Delta TM value showing the stabilisation of VRK3 produced by compound binding	A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. — Proc Natl Acad Sci U S A

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2L6	Abcam HeLa VRK3 KO	Cancer cell line	Female
CVCL_TX76	HAP1 VRK3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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