|Transcript ID (GRCh37/hg19)||ENST00000291552|
|Genomic Coordinates (GRCh37/hg19)||21:44524455-44524457|
|Tumor Type||Primary Site|
U2AF1 encodes for the small subunit of the U2 auxiliary factor, which is a non-small nuclear ribonucleoprotein (non-snRNP) required for the binding of U2 snRNP to the pre-mRNA branch site and plays critical role in RNA splicing. U2AF1 is one of several spliceosome complex genes frequently mutated in a variety of hematologic malignancies. Two hotspot mutations (S34 in exon 2 and Q157 in exon 6) occur within the two zinc-finger domains of the U2AF1 protein. These mutations have been reported in approximately 4- 9% of chronic myelomonocytic leukemia, 8-11% of cases of myelodysplastic syndrome (typically without ring sideroblasts), 16% of primary myelofibrosis, 12% of blastic plasmacytoid dendritic cell neoplasm, 4% of acute myeloid leukemia and 1% of essential thrombocythemia. U2AF1 mutations are associated with an unfavorable prognosis in myelodysplastic syndrome (NCCN Guidelines for Myelodysplastic Syndromes) and essential thrombocythemia, and decreased response to lenalidomide in myeloid neoplasms with and without del(5q). U2AF1 mutations are also reported to be highly specific for secondary acute myeloid leukemia, and may also be helpful in identifying a subset of therapy-related AML or elderly de novo AML with worse clinical outcomes. U2AF1 mutations have been associated with altered splicing patterns in vitro and in vivo, and may play a significant role in the pathogenesis of myeloid malignancies due to selective mis-splicing of tumor-associated genes.
U2AF1 is a splicing factor that regulates the removal of introns from pre-mRNAs to produce mature mRNAs. Somatic alterations involving the highly conserved serine at codon 34 are presumed to be pathogenic.