UPF3B

Chr XXLR

UPF3B regulator of nonsense mediated mRNA decay

Also known as: HUPF3B, MRX62, MRX82, MRXS14, RENT3B, UPF3BP1, UPF3BP2, UPF3BP3

NCBI Gene: 65109 ENSG00000125351 UniProt: Q9BZI7 OMIM: 300298

The protein is involved in nonsense-mediated decay of mRNAs containing premature stop codons by linking the exon junction complex to the NMD machinery and stimulating UPF1 helicase activity. Mutations cause X-linked syndromic intellectual developmental disorder. The gene shows X-linked recessive inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. The encoded protein is one of two functional homologs to yeast Upf3p. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. It forms with Y14 a complex that binds specifically 20 nt upstream of exon-exon junctions. This gene is located on the long arm of chromosome X. Two splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic 14MIM #300676

XLR

Clinical highlights

Gene-disease validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitivesufficient 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)

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P/LP submissions

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P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· G2P