Fig. 3: Molecular consequences of CD99L2 variants.
From: Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxia
a Transcript-level consequences of CD99L2 variants. Schematic representation of splicing effects caused by variants c.535 G > C, p.Gly179Arg, c.655+1 G > A, c.655+3 A > C and c.497-612_655+2267delinsC, as observed at the transcriptome level. Transcript c of variant c.655+1 G > A corresponds to ENST00000418547 (Ensembl transcript ID). For comparison, the exon and protein structure of CD99L2 are shown below (NCBI Reference Sequence: NP_113650.2; UniProt ID: Q8TCZ2-1). b RNA expression levels of CD99L2 (transcripts per million, tpm) in blood from 14 index patients grouped into the categories protein-truncating variants (PTV, blue; p.Arg128Ter, p.Arg131Ter, p.Gly156ValfsTer71, deletion including exons 2-11; min 0.15, lower whisker 3.16, lower quartile 3.27, median 3.87, upper quartile 4.5, upper whisker 4.61, max 6.82) and other mutations (green; c.655+1 G > A, c.655+3 A > C, p.Gly179Arg, deletion of exons 8/9; min/lower whisker 8.19, lower quartile 10.19, median 11.26, upper quartile 13.85, upper whisker/max 15.95), compared to 54 male controls (orange; min/lower whisker 9.26, lower quartile 16.0, median 18.30, upper quartile 21.43, upper whisker/max 26.86). c RNA expression of CD99L2 (tpm) in fibroblasts from eight index patients grouped into the categories PTV (blue; p.Arg128Ter, p.Arg131Ter, p.Gly156ValfsTer71; min/lower whisker 7.64, lower quartile 7.93, median 17.85, upper quartile 28.28, upper whisker/max 30.11) and other mutations (green; c.655+1 G > A, deletion of exons 8/9; min/lower whisker 55.67, lower quartile 57.02, median 64.17, upper quartile 82.18, upper whisker/max 116.08), compared to six male controls (orange; min 96.65, lower whisker 108.46, lower quartile 108.61, median 109.37, upper quartile 114.40, upper whisker/max 119.44). d–i Western blot of CD99L2 in primary fibroblasts from healthy controls (ctrl) and patients (indicated in red script), using an N-terminal CD99L2 antibody. Grey arrowheads indicate CD99L2-specific bands in controls, blue arrowheads C-terminally truncated CD99L2 (g, h), and the purple arrowhead an internally truncated form (i). GAPDH served as loading control. Source data are provided as a Source Data file.
