DYRK3

dual specificity tyrosine phosphorylation regulated kinase 3

Basic information

Region (hg38): 1:206635535-206684419

Links

ENSG00000143479 ∙ NCBI:8444 ∙ OMIM:603497 ∙ HGNC:3094 ∙ Uniprot:O43781 ∙ 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 DYRK3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYRK3 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		1
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	23	1	0

Variants in DYRK3

This is a list of pathogenic ClinVar variants found in the DYRK3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-206637702-C-G		not specified	Uncertain significance (Mar 28, 2024)
1-206637703-C-T		not specified	Uncertain significance (Nov 18, 2022)
1-206647401-A-G		not specified	Uncertain significance (Apr 08, 2022)
1-206647445-A-T		not specified	Uncertain significance (Oct 02, 2023)
1-206647556-A-C		not specified	Uncertain significance (Apr 08, 2022)
1-206647577-G-A		not specified	Uncertain significance (Jun 12, 2023)
1-206647584-C-T		not specified	Uncertain significance (Mar 28, 2024)
1-206647755-A-G		not specified	Uncertain significance (Oct 18, 2021)
1-206647772-G-A		not specified	Uncertain significance (Apr 23, 2024)
1-206647778-G-T		not specified	Uncertain significance (Jan 26, 2022)
1-206647915-G-T		not specified	Uncertain significance (Jan 19, 2024)
1-206647940-C-T		not specified	Uncertain significance (Nov 29, 2023)
1-206647962-G-A		not specified	Uncertain significance (Jul 05, 2023)
1-206647988-G-A		not specified	Uncertain significance (Jul 12, 2022)
1-206647991-A-G		not specified	Uncertain significance (May 31, 2023)
1-206648018-A-T		not specified	Uncertain significance (Apr 18, 2024)
1-206648025-A-G		not specified	Uncertain significance (Sep 22, 2023)
1-206648035-A-T			Likely benign (Mar 01, 2024)
1-206648103-A-G		not specified	Uncertain significance (May 17, 2023)
1-206648135-C-T		not specified	Uncertain significance (Oct 03, 2022)
1-206648271-C-T		not specified	Uncertain significance (Sep 17, 2021)
1-206648282-G-A		not specified	Uncertain significance (Jun 17, 2022)
1-206648366-A-G		not specified	Uncertain significance (Jun 05, 2024)
1-206648375-T-C		not specified	Uncertain significance (Mar 31, 2023)
1-206648607-G-A		not specified	Uncertain significance (Apr 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYRK3	protein_coding	protein_coding	ENST00000367109	3	48884

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000358	0.820	125645	1	102	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.186	302	311	0.970	0.0000173	3858
Missense in Polyphen		167	181.79	0.91863		2274
Synonymous	-1.09	126	111	1.13	0.00000548	1174
Loss of Function	1.36	11	17.1	0.645	9.43e-7	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00157	0.00157
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000317	0.000316
Middle Eastern	0.000381	0.000381
South Asian	0.000229	0.000229
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:9748265, PubMed:29634919). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear- envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}.
• Pathway: EGFR1 (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.916
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.96

Haploinsufficiency Scores

• pHI: 0.187
• hipred: N
• hipred_score: 0.408
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.745

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dyrk3
• Phenotype: hematopoietic system phenotype

Gene ontology

• Biological process: protein phosphorylation;cell cycle;peptidyl-tyrosine phosphorylation;erythrocyte differentiation;nuclear speck organization;stress granule disassembly;negative regulation of apoptotic process;negative regulation of DNA damage response, signal transduction by p53 class mediator;cell division;regulation of cellular response to stress;positive regulation of cell cycle G2/M phase transition;organelle disassembly;regulation of TORC1 signaling
• Cellular component: pericentriolar material;nucleus;nucleoplasm;cytoplasm;cytosol;cytoplasmic stress granule;nuclear speck;intracellular membrane-bounded organelle
• Molecular function: magnesium ion binding;protein kinase activity;protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;protein tyrosine kinase activity;ATP binding