UBTF

Chr 17AD

upstream binding transcription factor

Also known as: CONDBA, NOR-90, UBF, UBF-1, UBF1, UBF2

NCBI Gene: 7343 ENSG00000108312 UniProt: P17480 OMIM: 600673

This protein recognizes ribosomal RNA gene promoters and activates transcription by RNA polymerase I, playing a critical role in ribosome biogenesis. Mutations cause childhood-onset neurodegeneration with brain atrophy, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.06), indicating that even heterozygous disruption can cause severe disease.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the HMG-box DNA-binding protein family. The encoded protein plays a critical role in ribosomal RNA transcription as a key component of the pre-initiation complex, mediating the recruitment of RNA polymerase I to rDNA promoter regions. The encoded protein may also play important roles in chromatin remodeling and pre-rRNA processing, and its activity is regulated by both phosphorylation and acetylation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3, 11 and X and the long arm of chromosome 11. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodegeneration, childhood-onset, with brain atrophyMIM #617672

Clinical highlights

Gene-disease validity (ClinGen)

childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.06

LOEUF· LoF intol.

GOF*

Mechanism· G2P