VRK3

VRK serine/threonine kinase 3

Basic information

Region (hg38): 19:49976467-50025946

Links

ENSG00000105053 ∙ NCBI:51231 ∙ OMIM:619771 ∙ HGNC:18996 ∙ Uniprot:Q8IV63 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VRK3 gene.

• Inborn genetic diseases (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VRK3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			12			12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	0	0

Variants in VRK3

This is a list of pathogenic ClinVar variants found in the VRK3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-49979116-A-G		not specified	Uncertain significance (Dec 13, 2021)
19-49980985-C-T		not specified	Uncertain significance (Dec 27, 2023)
19-49988411-C-T		not specified	Uncertain significance (Nov 02, 2023)
19-49988444-T-C		not specified	Uncertain significance (Nov 09, 2023)
19-49989714-C-A		not specified	Uncertain significance (Jan 10, 2023)
19-49989726-C-T		not specified	Uncertain significance (Nov 17, 2022)
19-49989740-C-T		not specified	Uncertain significance (Dec 18, 2023)
19-49989753-C-A		not specified	Uncertain significance (Dec 19, 2023)
19-49992888-A-G		not specified	Uncertain significance (Oct 03, 2022)
19-49994870-C-T		not specified	Uncertain significance (May 09, 2023)
19-49997524-C-T		not specified	Uncertain significance (Nov 06, 2023)
19-49997545-T-C		not specified	Uncertain significance (Aug 31, 2022)
19-50007694-T-C		not specified	Uncertain significance (Nov 10, 2022)
19-50007718-G-A		not specified	Uncertain significance (Dec 17, 2023)
19-50007754-C-A		not specified	Uncertain significance (Oct 26, 2021)
19-50009254-A-G		not specified	Likely benign (Feb 21, 2024)
19-50009361-C-T		not specified	Uncertain significance (Dec 19, 2023)
19-50016039-C-T		not specified	Uncertain significance (Aug 01, 2022)
19-50016048-T-C		not specified	Uncertain significance (Jun 06, 2023)
19-50016098-C-T		not specified	Uncertain significance (Feb 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VRK3	protein_coding	protein_coding	ENST00000599538	12	49480

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.24e-11	0.489	125645	0	102	125747	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.572	242	268	0.902	0.0000149	3082
Missense in Polyphen		92	107.42	0.85642		1211
Synonymous	-0.243	112	109	1.03	0.00000630	915
Loss of Function	1.26	20	27.1	0.739	0.00000141	297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000590	0.000589
Ashkenazi Jewish	0.00248	0.00248
East Asian	0.000217	0.000217
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000423	0.000422
Middle Eastern	0.000217	0.000217
South Asian	0.000198	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus. {ECO:0000250, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:19141289}.
• Pathway: Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Signaling by Interleukins;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Innate Immune System;Immune System;Nuclear Events (kinase and transcription factor activation);ERKs are inactivated;Signaling by NTRK1 (TRKA);Signaling by NTRKs;ERK/MAPK targets;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade (Consensus)

Recessive Scores

• pRec: 0.0818

Intolerance Scores

• loftool: 0.926
• rvis_EVS: 0.89
• rvis_percentile_EVS: 89.24

Haploinsufficiency Scores

• pHI: 0.0731
• hipred: N
• hipred_score: 0.173
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Vrk3
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;positive regulation of phosphoprotein phosphatase activity;negative regulation of ERK1 and ERK2 cascade
• Cellular component: nucleus;nucleolus;cytoplasm;intracellular membrane-bounded organelle
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;protein phosphatase binding