Extended Data Fig. 3: RNU4-2 genotype–phenotype correlations.

a, Hierarchical clustering of the clinical features (n = 44, rows) of patients with pathogenic (P) and likely pathogenic (LP) RNU4-2 variants (n = 129, columns). Categorical data were converted to 0–1 scale, and values were z-score scaled for each row. Blue–yellow–red scale depicts z scores. Lower values indicate a more favorable phenotype, while higher values represent a more severe phenotype. Missing values are shown in gray. Columns are colored based on the variant classification (purple, pathogenic; light purple, likely pathogenic), its location within the distinct U4:U6 domains (stem I, light blue; quasi-pseudoknot, orange; RBM42 interaction region, blue; stem III, green) and the nucleotide change (color shades related to their position within the respective U4:U6 domain). Rows are colored on the category of the clinical feature (shades of pink and green). b–d, Details of the principal component analysis of clinical features associated with RNU4-2 LP/P variants presented in Fig. 3a. b, Percentage of explained variance by the first 10 principal components (PC). c, Top clinical features contributing to PC1. d, Top clinical features contributing to PC2. The horizontal red line represents the expected level of contribution if the contributions were uniform. Only variables with values above the red line are shown.