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): Report of a large family with a nonsense mutation in UPF3B that segregates with X-linked intellectual disability in males. Carrier females were phenotypically normal and had skewed X-inactivation.
20479756 Addington (2011): Report of two brothers found to have a frameshift mutation 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): Report of three families with syndromic X-linked intellectual disability who had truncating mutations in UPF3B. One family with a frameshift mutation had been previously given a clinical diagnosis of FG syndrome. The other two families, one frameshift and one nonsense mutation, had been given clinical diagnoses of Lujan-Fryns syndrome. Carrier females were all unaffected.

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.