ClinGen Dosage Sensitivity Curation Page

UPF3B

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
19238151 Laumonnier (2010): This group screened UPF3B coding sequence in 397 families collected by the EuroMRX consortium, and identified one nonsense variant, c.1081C>T/p.Arg361*, in a family with nonspecific intellectual disability (ID) (MRX62). This variant co-segregated with the disease in the family for the 47 other individuals, including ten affected men in two generations and 14 tested carrier women. Carrier females were phenotypically normal and had skewed X-inactivation.
20479756 Addington (2011): Report of two brothers found to have a frameshift variant (p.Q228fsX18) in UPF3B, inherited from a normal mother who had moderately skewed X-inactivation. One brother had childhood onset schizophrenia, pervasive developmental delay NOS, and ADHD. The other brother had congenital pulmonary stenosis, autism, and ADHD.
17704778 Tarpey (2007): This group systematically sequenced 737 genes in 250 families with X-linked ID, and identified LOF mutations in UPF3B in three families. One family with a frameshift mutation (p.G290fs*2) had been previously given a clinical diagnosis of FG syndrome. The other two families, with one frameshift and one nonsense variant (p.R225fs*20 and p.R430*) respectively, had been given clinical diagnoses of Lujan-Fryns syndrome. Carrier females were all unaffected.
22957832 Xu (2013): These authors used exome sequencing to identify the variant p.R430X in the UPF3B gene in an ID pedigree. This variant cosegregated with disease in this family, including four affected males and four carrier females.
31737052 Tejada (2019): this group identified a novel nonsense variant (c.118C > T; p.Gln40*) in UPF3B in a large Spanish Basque family with five affected males with intellectual disability and wide phenotypic variability.
22609145

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.