ClinVar

In 12 affected members of a 4-generation Chinese family with autosomal dominant retinitis pigmentosa mapping to chromosome 2cen-q12.1 (RP33; 610359), previously studied by Zhao et al. (2006), Zhao et al. (2009) identified a 3260C-T transition in exon 25 of the SNRNP200 gene, resulting in a ser1087-to-leu (S1087L) substitution at a highly conserved residue within the 'ratchet' helix of the first Sec63 domain. The mutation was not found in 13 unaffected family members or in 400 unaffected controls. Assays in budding yeast revealed that a mutation corresponding to S1087L markedly impaired ATP-dependent unwinding of U4/U6 small nuclear RNAs.

Cvackova et al. (2014) found that the S1087L substitution had no effect on targeting of BBR2 to nuclear speckles or incorporation of BRR2 into snRNPs. However, the mutation reduced the time with which BRR2 interacted with pre-mRNAs during splicing and increased the use of cryptic splice sites in a reporter based on the beta-globin gene (HBB; 141900). Splicing of other reporter genes was not affected, suggesting gene-specific effects of the mutation on 5-prime splice site selection.