VRK1

VRK serine/threonine kinase 1

Basic information

Region (hg38): 14:96797303-96954846

Links

ENSG00000100749 ∙ NCBI:7443 ∙ OMIM:602168 ∙ HGNC:12718 ∙ Uniprot:Q99986 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 1A (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 1A (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 1A (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 1 (Supportive), mode of inheritance: AR
• microcephaly-complex motor and sensory axonal neuropathy syndrome (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 1A (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia type 1A (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia type 1A; Neuronopathy, distal hereditary motor, autosomal recessive 10	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	19646678; 21937992; 24126608; 30847374; 31090908; 31837156; 35641352; 37257665

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VRK1 gene.

• Pontocerebellar hypoplasia type 1A (391 variants)
• not provided (73 variants)
• Inborn genetic diseases (53 variants)
• Congenital pontocerebellar hypoplasia type 1 (26 variants)
• not specified (20 variants)
• Neuronopathy, distal hereditary motor, autosomal recessive 10 (5 variants)
• Distal spinal muscular atrophy (4 variants)
• Pontoneocerebellar hypoplasia (3 variants)
• Pontocerebellar hypoplasia type 1B (1 variants)
• Multiple congenital anomalies (1 variants)
• Spinal muscular atrophy (1 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)
• EMG: neuropathic changes;Microcephaly-complex motor and sensory axonal neuropathy syndrome (1 variants)
• Juvenile amyotrophic lateral sclerosis (1 variants)
• Abnormality of the musculature (1 variants)
• Isolated microphthalmia 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VRK1 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			1	108	2	111
missense	1	2	119			122
nonsense	14	1				15
start loss						0
frameshift	24	5	3			32
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	11	1			13
splice region			7	29	4	40
non coding			10	65	27	102
Total	40	19	136	173	29

Highest pathogenic variant AF is 0.0000461

Variants in VRK1

This is a list of pathogenic ClinVar variants found in the VRK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-96797343-C-T		Pontoneocerebellar hypoplasia	Likely benign (Jun 14, 2016)
14-96797372-C-T		Pontoneocerebellar hypoplasia	Uncertain significance (Jun 14, 2016)
14-96797405-G-C		not specified	Likely benign (Feb 05, 2018)
14-96797429-G-T		not specified	Likely benign (Jan 16, 2018)
14-96797442-C-T		Pontocerebellar hypoplasia type 1A	Uncertain significance (Apr 27, 2017)
14-96797538-C-T			Benign (May 26, 2021)
14-96797592-T-C			Benign (Jul 03, 2018)
14-96833254-G-A			Benign (Jun 19, 2018)
14-96833321-A-G		Pontocerebellar hypoplasia type 1A	Likely benign (Nov 12, 2022)
14-96833460-G-C			Likely benign (Sep 16, 2019)
14-96833463-A-G		VRK1-related disorder	Likely benign (Apr 01, 2019)
14-96833476-CT-C		Pontocerebellar hypoplasia type 1A	Pathogenic (Aug 31, 2023)
14-96833478-C-T		Pontocerebellar hypoplasia type 1A	Uncertain significance (Dec 27, 2021)
14-96833478-CG-TT		Congenital pontocerebellar hypoplasia type 1 • Inborn genetic diseases	Uncertain significance (Mar 19, 2021)
14-96833479-G-A		Pontocerebellar hypoplasia type 1A	Uncertain significance (Sep 01, 2021)
14-96833479-GT-G		Pontocerebellar hypoplasia type 1A	Pathogenic (Dec 26, 2022)
14-96833480-T-G		Pontocerebellar hypoplasia type 1A	Likely benign (Feb 04, 2022)
14-96833483-A-T		Pontocerebellar hypoplasia type 1A	Likely benign (Apr 25, 2022)
14-96833492-T-C		Pontocerebellar hypoplasia type 1A	Likely benign (Jul 12, 2023)
14-96833493-C-T		Pontocerebellar hypoplasia type 1A	Pathogenic (Feb 21, 2022)
14-96833497-C-T		Pontocerebellar hypoplasia type 1A	Uncertain significance (Aug 31, 2021)
14-96833500-G-A		Congenital pontocerebellar hypoplasia type 1 • Inborn genetic diseases • Pontocerebellar hypoplasia type 1A	Uncertain significance (Jun 21, 2022)
14-96833502-A-T		Pontocerebellar hypoplasia type 1A	Pathogenic (Jul 10, 2023)
14-96833510-C-T		Pontocerebellar hypoplasia type 1A	Likely benign (Jul 19, 2023)
14-96833516-A-G		not specified • Pontocerebellar hypoplasia type 1A • Isolated microphthalmia 2	Benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VRK1	protein_coding	protein_coding	ENST00000216639	12	134419

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00211	0.997	125710	0	36	125746	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.17	167	215	0.776	0.0000113	2603
Missense in Polyphen		30	58.009	0.51716		678
Synonymous	0.570	61	66.9	0.911	0.00000330	688
Loss of Function	2.94	9	24.8	0.363	0.00000133	308

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000149
Ashkenazi Jewish	0.00159	0.00159
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000977	0.0000967
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.000355	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates 'Thr- 18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. 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 ATF2 which activates its transcriptional activity. {ECO:0000269|PubMed:10951572, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:15105425, ECO:0000269|PubMed:16495336, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:19103756}.
• Disease: DISEASE: Pontocerebellar hypoplasia 1A (PCH1A) [MIM:607596]: A disorder 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. {ECO:0000269|PubMed:19646678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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: 0.103

Intolerance Scores

• loftool: 0.848
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.69

Haploinsufficiency Scores

• pHI: 0.720
• hipred: Y
• hipred_score: 0.756
• ghis: 0.714

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vrk1
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; normal phenotype; reproductive system phenotype

Gene ontology

• Biological process: protein phosphorylation;mitotic nuclear envelope disassembly;mitotic nuclear envelope reassembly;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;histone H3-S10 phosphorylation;protein autophosphorylation;cell division;histone H3-T3 phosphorylation;Golgi disassembly
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;Golgi stack;spindle;cytosol
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;protein kinase binding;nucleosomal histone binding;histone kinase activity (H3-S10 specific);histone kinase activity (H3-T3 specific)