DYRK1A
Basic information
Region (hg38): 21:37365573-37526358
Previous symbols: [ "DYRK1", "DYRK", "MNBH" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
- 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 208 | 216 | ||||
missense | 13 | 33 | 274 | 86 | 38 | 444 |
nonsense | 47 | 10 | 57 | |||
start loss | 1 | 1 | ||||
frameshift | 107 | 18 | 129 | |||
splice donor/acceptor (+/-2bp) | 14 | 14 | 28 | |||
Total | 182 | 75 | 284 | 294 | 40 |
Highest pathogenic variant AF is 0.00015748937
GnomAD
Source:
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:
- 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