GPATCH11

Cilia effects upon perturbation of GPATCH11

Ciliogenesis screen results (1 screen)

• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Ciliopathy associations

• Retinal Dystrophy/Degeneration

Subcellular localization

basal body, nucleoplasm

Functional category

• Metabolism

Function

Biallelic mutations in GPATCH11 lead to severe early-onset photoreceptor degeneration, neurological issues, and skeletal abnormalities in humans. Analysis of exome datasets from affected individuals of four independent families identified variants in a new gene, GPATCH11. The aim of the study was to determine the genetic source of the patients’ symptoms and characterize the role of GPATCH11. Using engineered disease variants in mice, we showed abnormal levels of spliceosome components in mutant retinas and substantial splicing deregulation, indicating a role for GPATCH11 in spliceosome homeostasis and splicing activity. Additionally, we identified deregulated gene expression, partly independent of splicing abnormalities, suggesting the involvement of GPATCH11 in transcriptional regulation. The affected genes were found to be related to phototransduction and the transmission of visual messages, protein homeostasis, RNA homeostasis, and cilia metabolism. The presence of GPATCH11 in ciliary basal bodies further suggests a potential role in ciliary functions. Studying GPATCH11 dysfunction elucidates the complex roles of this protein in RNA metabolism, highlighting the significance of GPATCH11 in maintaining proper gene expression and its contributions to various aspects of retinal, neurological, and skeletal function or development (PMID: 39572588).