PHD finger-like domain-containing protein 5A (PHF5A)

PHD finger-like domain-containing protein 5A (PHF5A) is a highly conserved, small nuclear protein and vital component of the SF3B spliceosome complex[3][4][5]. It contains a characteristic PHD-finger domain that mediates critical protein-protein and protein-DNA contacts during pre-mRNA splicing, specifically enabling branchpoint adenosine recognition and accurate intron removal in both major and minor spliceosome assemblies[3][4][5]. Beyond splicing, PHF5A participates in chromatin remodeling, guiding deposition of histone modifications (H3K79me2, H3K36me3), and regulates transcription elongation in association with the PAF1 complex, which is crucial for stem cell pluripotency and self-renewal[3][5]. PHF5A also modulates DNA damage repair—particularly during antibody class switch recombination—by recruiting H2A variant histones and NHEJ DNA repair proteins to damage sites, maintaining genomic integrity[2]. Deregulation or overexpression of PHF5A has been implicated in oncogenesis across diverse tissues, where it controls alternative splicing programs, cell survival, tumor immunity, and resistance to certain chemotherapeutics[1][4][6]. It is under investigation as a diagnostic and prognostic biomarker, and as a selective target for cancer therapeutics using spliceosome inhibitors, although its essential roles in normal cell biology pose safety and selectivity challenges for clinical intervention[1][2][4][6].

Other names

Splicing factor 3B-associated 14 kDa proteinSplicing factor 3b, subunit 7SF3B7SF3b14bRds3INISAP14bbK223H9.2MGC1346PHD finger protein 5APHD-finger 5a

Inhibitors may block PHF5A's role in spliceosome assembly, specifically disrupting branch-point recognition and splicing fidelity[2][4] Cancer cell selective: Tumor cells exhibit higher dependency on PHF5A, rendering them more sensitive to splicing modulators/inhibitors[2][4][6]