DYRK1A

dual specificity tyrosine phosphorylation regulated kinase 1A

Basic information

Region (hg38): 21:37365573-37526358

Previous symbols: [ "DYRK1", "DYRK", "MNBH" ]

Links

ENSG00000157540 ∙ NCBI:1859 ∙ OMIM:600855 ∙ HGNC:3091 ∙ Uniprot:Q13627 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• DYRK1A-related intellectual disability syndrome (Definitive), mode of inheritance: AD
• DYRK1A-related intellectual disability syndrome (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 7	AD	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	Craniofacial; Neurologic	18405873; 21294719; 23099646; 23160955

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DYRK1A gene.

• DYRK1A-related_intellectual_disability_syndrome (808 variants)
• not_provided (299 variants)
• Inborn_genetic_diseases (116 variants)
• not_specified (81 variants)
• Intellectual_disability (36 variants)
• DYRK1A-related_disorder (23 variants)
• Complex_neurodevelopmental_disorder (18 variants)
• Microcephaly (9 variants)
• Absent_or_delayed_speech_development (9 variants)
• Deeply_set_eye (9 variants)
• Feeding_difficulties (8 variants)
• Seizure (8 variants)
• Global_developmental_delay (3 variants)
• See_cases (3 variants)
• Neurodevelopmental_disorder (2 variants)
• Male_infertility_with_spermatogenesis_disorder (2 variants)
• Autism_spectrum_disorder (1 variants)
• Intellectual_disability_syndrome_due_to_a_DYRK1A_point_mutation (1 variants)
• Generalized-onset_seizure (1 variants)
• SUDDEN_INFANT_DEATH_SYNDROME (1 variants)
• Microphthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYRK1A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001347721.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	208	2	216
missense	13	33	274	86	38	444
nonsense	47	10				57
start loss	1					1
frameshift	107	18	4			129
splice donor/acceptor (+/-2bp)	14	14				28
Total	182	75	284	294	40

Highest pathogenic variant AF is 0.00015748937

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYRK1A	protein_coding	protein_coding	ENST00000398960	11	151662

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000330	125707	0	5	125712	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.34	246	444	0.554	0.0000250	5048
Missense in Polyphen		39	145.48	0.26808		1677
Synonymous	-1.48	179	156	1.15	0.00000878	1454
Loss of Function	5.11	3	36.2	0.0828	0.00000202	401

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Exhibits a substrate preference for proline at position P+1 and arginine at position P- 3. Has pro-survival function and negatively regulates the apoptotic process. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis (By similarity). {ECO:0000250|UniProtKB:Q61214, ECO:0000250|UniProtKB:Q9NR20, ECO:0000269|PubMed:20981014, ECO:0000269|PubMed:21127067, ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:8769099}.
• Disease: DISEASE: Mental retardation, autosomal dominant 7 (MRD7) [MIM:614104]: A disease characterized by primary microcephaly, severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21294719, ECO:0000269|PubMed:23160955}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HH-Ncore;T-Cell Receptor and Co-stimulatory Signaling;Hedgehog;TCR;G0 and Early G1;Mitotic G1-G1/S phases;EGFR1;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.316

Intolerance Scores

• loftool: 0.220
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.64

Haploinsufficiency Scores

• pHI: 0.654
• hipred: Y
• hipred_score: 0.739
• ghis: 0.659

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dyrk1a
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of alternative mRNA splicing, via spliceosome;protein phosphorylation;nervous system development;circadian rhythm;viral process;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;peptidyl-tyrosine phosphorylation;negative regulation of microtubule polymerization;positive regulation of RNA splicing;amyloid-beta formation;peptidyl-serine autophosphorylation;peptidyl-tyrosine autophosphorylation;negative regulation of DNA damage response, signal transduction by p53 class mediator;protein autophosphorylation;negative regulation of mRNA splicing, via spliceosome;positive regulation of protein deacetylation
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytoskeleton;nuclear speck;axon;dendrite;ribonucleoprotein complex
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;protein binding;ATP binding;identical protein binding;protein self-association;tau protein binding;tau-protein kinase activity