DYRK2

dual specificity tyrosine phosphorylation regulated kinase 2

Basic information

Region (hg38): 12:67648338-67665406

Links

ENSG00000127334 ∙ NCBI:8445 ∙ OMIM:603496 ∙ HGNC:3093 ∙ Uniprot:Q92630 ∙ 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 DYRK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYRK2 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			25			25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	25	0	1

Variants in DYRK2

This is a list of pathogenic ClinVar variants found in the DYRK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-67649166-C-T			Benign (Apr 10, 2018)
12-67649812-G-T		not specified	Uncertain significance (Aug 19, 2024)
12-67649920-G-A		not specified	Uncertain significance (Mar 07, 2024)
12-67649923-A-G		not specified	Uncertain significance (Jan 26, 2022)
12-67649940-C-T		not specified	Uncertain significance (Mar 01, 2023)
12-67649944-C-A		not specified	Uncertain significance (Aug 13, 2021)
12-67657112-G-A		not specified	Uncertain significance (Aug 14, 2024)
12-67657123-C-G		not specified	Uncertain significance (Jan 03, 2024)
12-67657131-A-G		not specified	Uncertain significance (Sep 20, 2023)
12-67657221-C-T		not specified	Uncertain significance (Mar 14, 2024)
12-67657281-G-A		not specified	Uncertain significance (Aug 02, 2023)
12-67657293-G-A		not specified	Uncertain significance (May 04, 2023)
12-67657397-A-G		not specified	Uncertain significance (Jun 14, 2024)
12-67657447-A-T		not specified	Uncertain significance (Dec 09, 2023)
12-67657483-G-T		not specified	Uncertain significance (Jun 05, 2024)
12-67657506-A-G		not specified	Uncertain significance (Sep 17, 2021)
12-67657509-G-A		not specified	Uncertain significance (May 28, 2024)
12-67657523-G-A		not specified	Uncertain significance (Sep 17, 2021)
12-67657649-G-A		not specified	Uncertain significance (Dec 19, 2022)
12-67657727-C-T		not specified	Uncertain significance (Oct 12, 2021)
12-67657748-A-G		not specified	Uncertain significance (Dec 10, 2024)
12-67658100-G-C		not specified	Uncertain significance (Mar 02, 2023)
12-67658126-A-C		not specified	Uncertain significance (Dec 10, 2024)
12-67658145-C-G		not specified	Uncertain significance (Apr 04, 2024)
12-67658157-C-T		not specified	Uncertain significance (May 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYRK2	protein_coding	protein_coding	ENST00000344096	3	17069

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00249	125721	0	2	125723	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	246	349	0.706	0.0000210	3932
Missense in Polyphen		64	142.33	0.44965		1545
Synonymous	0.360	138	143	0.962	0.00000890	1223
Loss of Function	3.88	0	17.6	0.00	9.36e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000882	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser- 641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}.
• Pathway: T-Cell Receptor and Co-stimulatory Signaling;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;p53 pathway (Consensus)

Recessive Scores

• pRec: 0.257

Intolerance Scores

• loftool: 0.0550
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.643
• hipred: Y
• hipred_score: 0.783
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.945

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dyrk2

Zebrafish Information Network

• Gene name: dyrk2
• Affected structure: Rohon-Beard neuron
• Phenotype tag: abnormal
• Phenotype quality: displaced to

Gene ontology

• Biological process: protein phosphorylation;cellular response to DNA damage stimulus;smoothened signaling pathway;peptidyl-tyrosine phosphorylation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;positive regulation of glycogen biosynthetic process;negative regulation of calcineurin-NFAT signaling cascade;regulation of signal transduction by p53 class mediator
• Cellular component: ubiquitin ligase complex;nucleus;nucleoplasm;cytoplasm;cytosol;ribonucleoprotein complex
• Molecular function: magnesium ion binding;protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;manganese ion binding