PUF60

Chr 8AD

poly(U) binding splicing factor 60

Also known as: FIR, RoBPI, SIAHBP1, VRJS

NCBI Gene: 22827 ENSG00000179950 UniProt: Q9UHX1 OMIM: 604819

The protein encoded by this gene is a DNA- and RNA-binding protein that regulates pre-mRNA splicing, transcription (including MYC repression), and apoptosis. Mutations cause Verheij syndrome, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.245), indicating that such mutations are likely to have significant clinical consequences.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nucleic acid-binding protein that plays a role in a variety of nuclear processes, including pre-mRNA splicing and transcriptional regulation. The encoded protein forms a complex with the far upstream DNA element (FUSE) and FUSE-binding protein at the myelocytomatosis oncogene (MYC) promoter. This complex represses MYC transcription through the core-TFIIH basal transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Verheij syndromeMIM #615583

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.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

0.24

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — PUF60