VRK2

VRK serine/threonine kinase 2

Basic information

Region (hg38): 2:57907628-58159920

Links

ENSG00000028116 ∙ NCBI:7444 ∙ OMIM:602169 ∙ HGNC:12719 ∙ Uniprot:Q86Y07 ∙ 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 VRK2 gene.

• Fanconi anemia (18 variants)
• Inborn genetic diseases (16 variants)
• Fanconi anemia complementation group L (13 variants)
• not provided (4 variants)
• not specified (3 variants)
• FANCL-related condition (1 variants)
• Fanconi anemia complementation group A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VRK2 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			2	1		3
missense			19	1		20
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding			9	10		19
Total	0	0	31	12	0

Variants in VRK2

This is a list of pathogenic ClinVar variants found in the VRK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-58048847-A-G		not specified	Uncertain significance (Oct 03, 2023)
2-58084112-A-G		not specified	Uncertain significance (Feb 26, 2024)
2-58084881-G-A		not specified	Uncertain significance (Dec 14, 2022)
2-58088354-G-C		not specified	Uncertain significance (Oct 26, 2021)
2-58088363-A-G		not specified	Uncertain significance (Jun 01, 2023)
2-58088415-A-G		not specified	Uncertain significance (Jun 23, 2023)
2-58088442-G-A		not specified	Uncertain significance (Nov 01, 2022)
2-58123117-A-G		not specified	Uncertain significance (Jan 29, 2024)
2-58123144-A-G		not specified	Uncertain significance (Jan 10, 2023)
2-58123192-G-A		not specified	Uncertain significance (Feb 05, 2024)
2-58123198-T-C		not specified	Uncertain significance (Dec 22, 2023)
2-58123206-A-G		not specified	Uncertain significance (Nov 01, 2022)
2-58131820-G-A		not specified	Uncertain significance (Mar 29, 2023)
2-58131827-C-G		not specified	Uncertain significance (Dec 21, 2021)
2-58131855-C-T		not specified	Uncertain significance (Dec 17, 2023)
2-58131856-G-A		not specified	Uncertain significance (Jan 12, 2024)
2-58139666-G-A		not specified	Uncertain significance (Dec 17, 2023)
2-58139726-A-G		not specified	Uncertain significance (Oct 25, 2022)
2-58139755-C-T		not specified	Uncertain significance (Dec 22, 2023)
2-58139792-A-G		not specified	Uncertain significance (Jan 24, 2024)
2-58146317-T-C		not specified	Uncertain significance (May 11, 2022)
2-58146365-G-A		not specified	Uncertain significance (Aug 02, 2021)
2-58146381-A-T		not specified	Uncertain significance (Dec 17, 2023)
2-58146397-A-G		not specified	Uncertain significance (Feb 26, 2024)
2-58146407-C-A		not specified	Uncertain significance (Nov 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VRK2	protein_coding	protein_coding	ENST00000435505	12	252270

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.57e-11	0.572	125647	0	100	125747	0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.949	300	257	1.17	0.0000122	3329
Missense in Polyphen		97	89.337	1.0858		1167
Synonymous	0.0845	89	90.0	0.989	0.00000449	901
Loss of Function	1.39	21	29.1	0.721	0.00000141	377

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000711	0.000710
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000225	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000534	0.000528
Middle Eastern	0.000225	0.000217
South Asian	0.000436	0.000425
Other	0.000663	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to ERBB2 and HRAS. Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant.
• Pathway: Clearance of Nuclear Envelope Membranes from Chromatin;Nuclear Envelope Breakdown;Mitotic Prophase;Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.0962

Intolerance Scores

• loftool: 0.999
• rvis_EVS: 0.07
• rvis_percentile_EVS: 58.96

Haploinsufficiency Scores

• pHI: 0.133
• hipred: N
• hipred_score: 0.336
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.951

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vrk2

Gene ontology

• Biological process: protein phosphorylation;viral process;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;cellular response to oxidative stress;regulation of MAPK cascade;protein autophosphorylation;regulation of interleukin-1-mediated signaling pathway
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;mitochondrial membrane;protein-containing complex
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;protein kinase binding;protein domain specific binding