Function
This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and U2 spliceosomal RNA, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms.
Interactions
Clinical relevance
Mutations in this gene have been recurrently seen in cases of advanced chronic lymphocytic leukemia, myelodysplastic syndromes and breast cancer. SF3B1 mutations are found in the vast majority of myelodysplastic syndrome with ring sideroblasts (MDS-RS) and MDS with ring sideroblasts and thrombocytosis (MDS-RS-T), so much so that mutated SF3B1 has become a diagnostic criterion for these per the 5th edition of the WHO Classification and the International Consensus Classification (ICC).
There is also an emerging body of evidence to suggest implications of SF3B1 mutations being involved in orbital melanoma.
