DYRK1A

Chr 21AD

dual specificity tyrosine phosphorylation regulated kinase 1A

Also known as: DYRK, DYRK1, HP86, MNB, MNBH, MRD7

NCBI Gene: 1859 ENSG00000157540 UniProt: Q13627 OMIM: 600855

This gene encodes a dual-specificity kinase that catalyzes autophosphorylation on serine/threonine and tyrosine residues and regulates cell proliferation and brain development. Mutations cause intellectual developmental disorder, autosomal dominant 7, predominantly through loss-of-function mechanisms. The gene shows extremely high constraint against loss-of-function variants (pLI 1.0, LOEUF 0.21), consistent with haploinsufficiency as the primary pathogenic mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene. It is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 7MIM #614104

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

151

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· G2P

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