DYRK1A

dual specificity tyrosine phosphorylation regulated kinase 1A

Basic information

Region (hg38): 21:37365573-37526358

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

Links

ENSG00000157540NCBI:1859OMIM:600855HGNC:3091Uniprot:Q13627AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder, autosomal dominant 7ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Neurologic18405873; 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.

EffectPLPVUSLBBSum
synonymous
6
clinvar
208
clinvar
2
clinvar
216
missense
13
clinvar
33
clinvar
274
clinvar
86
clinvar
38
clinvar
444
nonsense
47
clinvar
10
clinvar
57
start loss
1
1
frameshift
107
clinvar
18
clinvar
4
clinvar
129
splice donor/acceptor (+/-2bp)
14
clinvar
14
clinvar
28
Total 182 75 284 294 40

Highest pathogenic variant AF is 0.00015748937

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DYRK1Aprotein_codingprotein_codingENST00000398960 11151662
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.000.000330125707051257120.0000199
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.342464440.5540.00002505048
Missense in Polyphen39145.480.268081677
Synonymous-1.481791561.150.000008781454
Loss of Function5.11336.20.08280.00000202401

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001230.000123
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00002640.0000264
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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