Extended Data Fig. 6. Expression of shorter UNC13B isoform in human neuronal tissue masks detection of UNC13B fsE across NYGC tissue samples.

(a) Expression of splice junction reads supporting the UNC13B fsE across tissues and disease subtypes. Junction counts are normalised by library size in millions (junctions per million). Expression of UNC13B fsE is present across controls and ALS/FTLD-non-TDP tissues. Wilcoxon test, significance levels reported as * (p < 0.05) ** (p < 0.01) *** (p < 0.001) **** (p < 0.0001). (b) Diagram showing three of the UNC13B transcripts, including the APPRIS³⁵ principal isoform UNC13B-207 (blue), the NMD sensitive isoform UNC13B-208 (green), and the shorter isoform UNC13B-210 which shares the fsE (light green highlight) and one of the splicing junctions supporting the fsE as UNC13B-208. (c) Expression of three UNC13B isoforms across NYGC cohort and in the five in vitro TDP-43 knockdowns experiments^9,21. UNC13B-210 is expressed across in vivo human tissues, whereas there is almost no expression of UNC13B-210 in any of the in vitro experiments. Box plots (a, c): boundaries 25–75th percentiles; midline, median; whiskers, Tukey style.