The human DYRK1A (dual specificity tyrosine phosphorylation regulated kinase 1A) gene is located on chromosome 21 and is postulated to play a key role in the development of Down syndrome. Deviation from diploidy for DYRK1A appears to be deleterious in either direction: see DYRK1A haploinsufficiency syndrome (FBhh0001224, MIM:614104). There is a single high-scoring ortholog in Drosophila, mnb, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\mnb is also orthologous to a second human gene, DYRK1B.
The human DYRK1A gene has not been introduced into flies.
As is the case for the human gene, the precise level of Dmel\mnb expression and function appears to be important. Animals homozygous for loss-of-function mutations of mnb exhibit an extended developmental time course, defects in olfactory and visual behavior, neuroanatomy defects, and neurophysiology defects. Pan-neuronal overexpression of mnb causes age-dependent degeneration of brain neurons, accelerated age-dependent decline in motor performance, shortened lifespan, modified presynaptic structures and enhanced spontaneous transmitter release, and slowed recovery from short-term depression of synaptic transmission. Physical and genetic interactions have been described for Dmel\mnb; see below and in the mnb gene report.
[updated Jul. 2020 by FlyBase; FBrf0222196]
Down syndrome is characterized by a particular combination of phenotypic features that includes mental retardation and characteristic facial structure. Individuals with Down syndrome often have specific major congenital malformations such as those of the heart (30-40% in some studies) and of the gastrointestinal tract. 90% of Down syndrome patients have a significant hearing loss (Mazzoni et al., 1994; pubmed:7881226). A number of other diseases are observed at higher frequency among Down syndrome individuals, including leukemia (Robison, 1992; pubmed:1532221) and Alzheimer disease (Wisniewski et al., 1985; pubmed:3158266). [from MIM:190685; 2016.07.19]
DYRK1A 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. DYRK1A appears to play a significant role in a signaling pathway regulating cell proliferation and in brain development. [Gene Cards, DYRK1A; 2019.06.25]
Many to one: 2 human to 1 Drosophila; the second human gene is DYRK1B.
