This report concerns a newly described X-linked disease, GPKOW-associated multisystemic disorder. GPKOW encodes a component of the spliceosome. There is a single orthologous gene in Drosophila, Gpkow, for which a number of genetic reagents have been generated, including a loss-of-function mutation and RNAi-targeting constructs.
UAS constructs of the human Hsap\GPKOW gene have been introduced into flies, including wild-type and a terminal frameshift variant implicated in this disease; see the 'Disease-Implicated Variants' table below. Overexpression of the human GPKOW reference or the frameshift variant, using various drivers, results in lethality. Using the GMR eye-specific driver, eye size is reduced; some escapers survive to adulthood. Effects upon both eye size and survival to adulthood are more severe using the wild-type reference Hsap\GPKOW vs. the frameshift variant; thus, the variant is postulated to result in partial loss of function.
When homozygous, loss-of-function mutations of Dmel\Gpkow result in embryonic lethality. Gpkow is widely expressed, both in terms of tissue type and developmental stage. Inhibition of expression in the developing larval brain results in a microcephaly phenotype.
[updated Aug. 2025 by FlyBase; FBrf0222196]
Of three individuals observed, phenotypes included intrauterine growth restriction, severe brain and eye abnormalities, and skeletal abnormalities; all 3 were male; death occurred in the first year (Mok et al., 2025; pubmed:40221893; FBrf0262832).
This syndrome is X-linked; C-terminal frameshift variants in the GPKOW gene are implicated (Mok et al., 2025; pubmed:40221893; FBrf0262832).
GPKOW encodes a putative RNA-binding protein containing G-patch and KOW domains. The encoded protein interacts directly with protein kinase A and protein kinase X and is found associated with the spliceosome. [GeneCards, GPKOW; 2025.08.26]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human GPKOW (1 Drosophila to 1 human).
