Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA. It could also reverse aberrant GLA splicing in a PP1-dependant manner. Our findings revealed the alternative splicing mechanism of GLA (IVS4+919G>A), and a potential treatment for this specific genetic type of Fabry disease by amiloride in the future.
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PMID:Modulation the alternative splicing of GLA (IVS4+919G>A) in Fabry disease. 2843 Aug 23