The second of the top genes, BRSK2 is one of a pair of kinases (BRSK1/2) highly expressed in the mammalian brain [46], in particular the cerebellum, hippocampus and hypothalamus tissues (www.gtexportal.org). The enzyme encoded by BRSK2 localizes to presynaptic sites and modulates structural and functional maturation of synapses; indeed functional studies in mice indicate that the serine/threonine kinases (also known as SAD kinases) are critical for specification of axons and axonal development, and for playing a critical role in cell proliferation, differentiation and cell death [47]. The absence of SAD kinases does not prevent axon formation but does compromise maturation of axon terminals and mutations in SAD orthologs led to presynaptic defects in C. elegans [48] and Drosophila [49]. Gene ontology processes associated with BRSK2 include actin cytoskeleton reorganization, apoptotic signaling pathways and establishment of cell polarity (www.uniprot.org).
