GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330158/primaryOK200TranscriptomicsDanio rerioExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330158GEOGSEfalseBulk RNA-sequencing of single 6 dpf wild-type and osgep G177A homozygote larvaeThe OSGEP gene encodes a KEOPS (Kinase, Endopeptidase and Other Proteins of Small size) complex subunit catalyzing N6-threonylcarbamoyladenosine (t6A) modification to A37 of ANN tRNAs. This modification enhances the accuracy and efficiency of protein synthesis, and variants in OSGEP are linked to Galloway-Mowat syndrome, with clinical features including intellectual disability, developmental delay, seizures, microcephaly, other brain abnormalities and kidney problems. The KEOPS complex may also function in telomere length regulation, genome maintenance, and DNA damage response. OSGEP knockdown in human cells impairs cellular proliferation and translation, increases ER stress and apoptosis, activates the DNA damage response, and disrupts actin regulation. Frameshift zebrafish osgep mutants exhibit microcephaly, increased apoptosis in the brain, and early lethality. Based on human-genetic data, we generated a zebrafish osgep G177A knock-in mutant. osgepG177A/G177A larvae have reduced eye and head sizes relative to wildtype. The mutants become very small and about 70% of them die during the first 4-5 weeks post-fertilization. We determined that the p53 pathway is activated in osgepG177A/G177A embryos and leads to an increase in apoptosis. However, loss of tp53 does not rescue the morphological phenotypes or survival of osgep mutants. RNA-sequencing of single wildtype and osgepG177A/G177A larvae identified >1000 differentially-expressed genes. Up-regulated genes were significantly associated with protein folding, endoplasmic reticulum, RNA processing/maturation, and ribosome biogenesis. Down-regulated genes were strongly enriched among translation-related terms, developmental terms, immune and hematopoietic terms, inflammatory response as well as Ribosome, Proteasome, Ferroptosis, Apoptosis and Oxidative Phosphorylation pathways.2026/05/12GSE330158GSM9720138GSM9720137GSM9720139GSM9720136GSM9720141GSM9720140GSM9720143GSM972014224995330158Danio rerio