Upstream binding transcription factor (UBTF)

Upstream binding transcription factor (UBTF) is a member of the HMG-box DNA-binding protein family and functions as a key transcription factor regulating ribosomal RNA synthesis within the nucleolus. UBTF forms part of the pre-initiation complex and recruits RNA polymerase I to rDNA promoters, activating transcription. It also plays roles in chromatin remodeling and pre-rRNA processing. UBTF has two isoforms (UBTF1 and UBTF2); UBTF1 primarily regulates rRNA transcription (via RNA polymerase I), while UBTF2 affects mRNA transcription (via RNA polymerase II). Pathogenic de novo gain-of-function variants in UBTF1 are associated with severe, childhood-onset neurodegenerative and neurodevelopmental disorders, involving language, motor, and cognitive regression, often accompanied by brain atrophy and mitochondrial dysfunction. Merely altering UBTF expression—via overexpression or loss-of-function—can be deleterious to neural development and cellular metabolism. There are currently no approved drugs targeting UBTF directly. The rare identification of decreased CSF biopterin may act as a biomarker for UBTF1-related disease.

Other names

UBFUBF1UBF-1UBF2NOR-90Autoantigen NOR-90Nucleolar transcription factor 1Upstream-binding factor 190-kDa nucleolus organizer region autoantigenCONDBA

Not currently targeted by approved drugs; pathogenic variants act via gain-of-function leading to increased rRNA expression