STRC exon 1 conservation and NMD motifs
Constraint. E1 under strong negative selection (gnomAD pLI, Zoonomia). Loss of function via early stops = near-certain NMD substrate. NMD rule. PTC >50 nt upstream of last exon-exon junction → degraded by NMD. STRC has ~28 exon-junctions, so NMD strongly gates stop-gain alleles. ASO implications for h08.
- Skip E1 → frameshift → NMD → no protein. Bad.
- Skip in-frame exons only.
- Consider pseudoexon inclusion or 3’UTR modulators instead.
Connections
[applies]index[source]STRC ASO Phase1 Splice-Switch Design[part-of]STRC Gene