Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

DYRK1A

HGNC:3091 (protein-coding gene)

dual specificity tyrosine phosphorylation regulated kinase 1A

Unique Cases:
57
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
January 24, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
DYRK1A is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:21127067, PubMed:8769099, PubMed:30773093, PubMed:20981014, PubMed:23665168). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3 (PubMed:23665168). Plays an important role in double- strand breaks (DSBs) repair following DNA damage (PubMed:31024071). Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB s... (Source: Uniprot)
Previous symbols
DYRK1, DYRK, MNBH
Alias symbols
No alias sybmols
Chromosomal Location
21q22.13
Genomic Coordinates
GRCh37:chr21:38737875-38887679
GRCh38:chr21:37365573-37526358
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

3.69

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.21

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive2 Strong1

Publications:

Husson T et. al., Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use., Transl Psychiatry, 2020
Tran KT et. al., Genetic landscape of autism spectrum disorder in Vietnamese children., Sci Rep, 2020
Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020
Luco SM et. al., Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature., BMC Med Genet, 2016
Daoud H et. al., Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit., CMAJ, 2016
Rump P et. al., Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly., BMC Med Genomics, 2016
Helbig KL et. al., Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy., Genet Med, 2016
Lee H et. al., Clinical exome sequencing for genetic identification of rare Mendelian disorders., JAMA, 2014
Zhu X et. al., Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios., Genet Med, 2015
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Beighley JS et. al., Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes., Biol Psychiatry, 2020
O'Roak BJ et. al., Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders., Science, 2012
O'Roak BJ et. al., Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations., Nature, 2012
Redin C et. al., Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing., J Med Genet, 2014
Courcet JB et. al., The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy., J Med Genet, 2012
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Reuter MS et. al., Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders., JAMA Psychiatry, 2017
Coe BP et. al., Refining analyses of copy number variation identifies specific genes associated with developmental delay., Nat Genet, 2014
Ruaud L et. al., DYRK1A mutations in two unrelated patients., Eur J Med Genet, 2015
Okamoto N et. al., Targeted next-generation sequencing in the diagnosis of neurodevelopmental disorders., Clin Genet, 2015
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
van Bon BW et. al., Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly., Clin Genet, 2011
Qiao F et. al., A De Novo Mutation in DYRK1A Causes Syndromic Intellectual Disability: A Chinese Case Report., Front Genet, 2019
Peng Y et. al., [Identification of a de novo interstitial 21q22.12q22.13 deletion in a patient with intellectual disability]., Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2019
Iglesias A et. al., The usefulness of whole-exome sequencing in routine clinical practice., Genet Med, 2014
Guo YX et. al., Whole-Exome Sequencing for Identifying Genetic Causes of Intellectual Developmental Disorders., Int J Gen Med, 2021
Lee KS et. al., A novel de novo heterozygous DYRK1A mutation causes complete loss of DYRK1A function and developmental delay., Sci Rep, 2020
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
Zhao X et. al., Genetic analysis and identification of novel variations in Chinese patients with pediatric epilepsy by whole-exome sequencing., Neurol Sci, 2022
Lindstrand A et. al., Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability., Genet Med, 2022

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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