Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DYRK1A, dual-specificity tyrosine phosphorylation-regulated kinase 1A, which is linked to mental retardation and microcephaly, is a member of the CMGC group of kinases. It has both cytoplasmic and nuclear functions, however, molecular mechanisms of how DYRK1A regulates gene expression is not well understood. Here, we identify two histone acetyltransferases, p300 and CBP, as interaction partners of DYRK1A through a proteomics study. We show that overexpression of DYKR1A causes hyperphosphorylation of p300 and CBP. Using genome-wide location (ChIP-sequencing) analysis of DYRK1A, we show that most of the DYRK1A peaks co-localize with p300 and CBP, at enhancers or near the transcription start sites (TSS). Modulation of DYRK1A, by shRNA mediated reduction or transfection mediated overexpression, leads to alteration of expression of downstream located genes. We show that the knockdown of DYRK1A results in a significant loss of H3K27acetylation at these enhancers, suggesting that DYRK1A modulates the activity of p300/CBP at these enhancers. We propose that DYRK1A functions in enhancer regulation by interacting with p300/CBP and modulating their activity. Overall, DYRK1A function in the regulation of enhancer activity provides a new mechanistic understanding of DYRK1A mediated regulation of gene expression, which may help in better understanding of the roles of DYRK1A in human pathologies.
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PMID:DYRK1A interacts with histone acetyl transferase p300 and CBP and localizes to enhancers. 3013 13

Autosomal dominant mental retardation-7 (MRD7) is a rare anomaly, characterized by severe intellectual disability, feeding difficulties, behavior abnormalities, and distinctive facial features, including microcephaly, deep-set eyes, large simple ears, and a pointed or bulbous nasal tip. Some studies show that the disorder has a close correlation with variants in DYRK1A. Herein we described a Chinese girl presenting typical clinical features diagnosed at 4 years old. Whole-exome sequencing of the familial genomic DNA identified a novel mutation c.930C > A (p.Tyr310*) in exon 7 of DYRK1A in the proband. The nonsense mutation was predicted to render the truncation of the protein. Our results suggested that the de novo heterozygous mutation in DYRK1A was responsible for the MRD7 in this Chinese family, which both extended the knowledge of mutation spectrum in MRD7 patients and highlighted the clinical application of exome sequencing.
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PMID:A De Novo Mutation in DYRK1A Causes Syndromic Intellectual Disability: A Chinese Case Report. 3180 47


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