This report concerns a newly described neurodevelopmental disorder (NDD) associated with variants in the human SLK gene; this NDD exhibits autosomal recessive inheritance. The SLK gene is protein serine/threonine kinase involved in multiple processes, including cytoplasmic microtubule organization and regulation of focal adhesion assembly. There is a single orthologous gene in Drosophila, Slik, for which multiple genetic reagents have been generated, including a loss-of-function mutation, RNAi-targeting constructs, and overexpression constructs. Dmel\Slik is also ortholgous to the human gene STK10.
Multiple UAS constructs of the human Hsap\SLK gene have been introduced into flies, including wild-type and variants implicated in this disease. See the 'Disease-Implicated Variants' table below. Heterologous rescue (functional complementation) of Slik loss-of-function neural phenotypes is observed using the wild-type human gene, but not when using any of the disease-implicated variants.
Neural-specific loss of Slik, effected by RNAi, results in developmental defects of the larval neuromuscular junction, causing a locomotion defect observed in both larvae and adult flies; larvae also exhibit an enlarged ventral ganglion; adult flies exhibit a shortened lifespan.
[updated Aug. 2025 by FlyBase; FBrf0222196]
The phenotype of this disease, which is highly variable, includes developmental delay, varying levels of intellectual disability, hypotonia, and ocular abnormalities (Alabdi et al., 2025; pubmed:40347834; FBrf0262665).
Based on assessment of 3 families, this disease is linked to biallelic variants in SLK.
The SLK protein exhibits protein serine/threonine kinase activity; it is involved in multiple processes, including cytoplasmic microtubule organization and regulation of focal adhesion assembly. [from GeneCards, SLK; 2025.08.19]
Many to one: 2 human genes to 1 Drosophila gene.
High-scoring ortholog of human STK10 and SLK (1 Drosophila to 2 human).
