VRK1

VRK serine/threonine kinase 1

Basic information

Region (hg38): 14:96797304-96954846

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 (476 variants)
Inborn_genetic_diseases (72 variants)
not_provided (63 variants)
Congenital_pontocerebellar_hypoplasia_type_1 (29 variants)
Neuronopathy,_distal_hereditary_motor,_autosomal_recessive_10 (26 variants)
not_specified (19 variants)
Distal_spinal_muscular_atrophy (7 variants)
VRK1-related_disorder (4 variants)
Pontoneocerebellar_hypoplasia (3 variants)
Spinal_muscular_atrophy (2 variants)
Distal_hereditary_motor_neuropathy_associated_with_upper_motor_neuron_signs (2 variants)
Juvenile_amyotrophic_lateral_sclerosis (1 variants)
Abnormality_of_the_musculature (1 variants)
Pontocerebellar_hypoplasia_type_1B (1 variants)
Amyotrophic_lateral_sclerosis (1 variants)
EMG:_neuropathic_changes (1 variants)
Microcephaly-complex_motor_and_sensory_axonal_neuropathy_syndrome (1 variants)
Neuronopathy,_distal_hereditary_motor,_autosomal_recessive (1 variants)
Hereditary_breast_ovarian_cancer_syndrome (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. These statistics are base on transcript: NM_000003384.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	131 clinvar		137
missense		13 clinvar	145 clinvar	4 clinvar		162
nonsense	14 clinvar	3 clinvar				17
start loss						0
frameshift	24 clinvar	14 clinvar	2 clinvar			40
splice donor/acceptor (+/-2bp)	1 clinvar	17 clinvar	1 clinvar			19
Total	39	47	154	135	0

Highest pathogenic variant AF is 0.000047914946

Loading clinvar variants...

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)