Are mutations in UBR4 associated with Long QT syndrome or other cardiac arrhythmias in the 100K dataset?

Genomics England Research Registry ID:  257

Registered: 23/09/2019

Expert Summary

UBR4 is a single copy gene that is highly conserved across kingdoms. Recent work has shown that the plant homologue of UBR4 is involved in regulation of the circadian clock (Hearn et al., 2018 PMID:29997180). UBR4 has been demonstrated to have circadian and diurnal expression in mouse, and variants in UBR4 have been previously identified as candidate pathogenic mutations in Long QT syndrome (Shigemizu et al., 2015 PMID:26132555). Some instance of Long QT, such as Long QT3, appear to have circadian gating to their incidence, making this a good candidate disease for a circadian associated disease. This project will ascertain the frequency and occurrence of pathogenic mutations in UBR4 within the arrhythmia dataset. This will be supported by experimental validation in a zebrafish disease model.

Lay Summary

UBR4 is a gene found in both plants and animals. In humans it is potentially involved in Long QT syndrome, and we have previously shown it to be a regulator of the biological or circadian clock in plants. We have evidence to show it is involved in circadian regulation in animals, and this project is to identify if there are any variants in UBR4 which are associated with Long QT syndrome within the 100K dataset. Links between biological clocks and diseases are a relatively unexplored area, and this project will look at one such candidate gene and disease.