protein
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Gene
DYRK1A
Organism
Homo sapiens(9606)
Length
763 aa
Mass
85,584 Da
DYRK1A encodes a dual-specificity kinase with both serine/threonine and tyrosine kinase activities (UniProt: Q13627). The protein plays multiple roles in cellular regulation, including phosphorylation of RNF169 to promote homologous recombination repair following DNA damage, and phosphorylation of RNA polymerase II's CTD to regulate transcription. DYRK1A also modulates alternative splicing via SRSF6 phosphorylation and promotes cell survival under genotoxic stress through SIRT1-mediated inhibition of p53-dependent apoptosis.
DYRK1A is implicated in intellectual developmental disorder, autosomal dominant 7 (MRD7), characterized by microcephaly, severe intellectual disability, autistic behavior, and dysmorphic facial features. The protein's broad involvement in DNA repair, transcriptional control, and cell survival pathways suggests its dysfunction disrupts neurodevelopmental processes.
DYRK1A is classified as a SFARI Category 1 gene with syndromic involvement (SFARI Cat 1, syndromic), indicating high-confidence association with autism spectrum disorder within a broader developmental syndrome context.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). 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 sites thereby promoting homologous recombination repair (HRR) (PubMed:30773093). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:25620562, PubMed:29849146). May play a role in a signaling pathway regulating nuclear functions of cell proliferation (PubMed:14500717). Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Has pro-survival function and negatively regulates the apoptotic process (By similarity). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1 (By similarity). This in turn inhibits p53/TP53 activity and apoptosis (By similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (By similarity)
Disease associations
Intellectual developmental disorder, autosomal dominant 7MRD7
A disease characterized by primary microcephaly, severe intellectual disability without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Intellectual disability is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Sources
Last updated 5/6/2026, 5:25:39 AM