UPF3B |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- UPF3B (HGNC:20439) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- UPF3B regulator of nonsense mediated mRNA decay
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MRX62, UPF3BP1, UPF3BP2, UPF3BP3
- Alias symbols
- RENT3B, UPF3X, HUPF3B, MRX82
- %HI
- 33.04(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.98(Read more about gnomAD pLI score)
- LOEUF
- 0.29(Read more about gnomAD LOEUF score)
- Cytoband
- Xq24
- Genomic Coordinates
-
GRCh37/hg19: chrX:118967985-118986926 NCBI Ensembl UCSC GRCh38/hg38: chrX:119805311-119852963 NCBI Ensembl UCSC - MANE Select Transcript
- NM_080632.3 ENST00000276201.7 (Read more about MANE Select)
- Function
- Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase act... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- syndromic X-linked intellectual disability 14 Monarch
-
PUBMED:
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.
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PUBMED:
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.
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PUBMED:
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.
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PUBMED:
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.
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PUBMED:
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.
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PUBMED:
22609145
Lynch (2012): this group identified a frameshift variant in exon 7 of UPF3B, c.697_698delAG, p.Arg233fs*30 in two affected brothers with variable degrees of developmental delay and their carrier mother.
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 (TS) Score Details
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.