Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

UPF3B

HGNC:20439 (protein-coding gene)

UPF3B regulator of nonsense mediated mRNA decay

Unique Cases:
15
Disorders:
ID, ASD, EP, ADHD, SCZ, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
UPF3B is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene 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)
Previous symbols
MRX62, UPF3BP1, UPF3BP2, UPF3BP3
Alias symbols
RENT3B, UPF3X, HUPF3B, MRX82
Chromosomal Location
Xq24
Genomic Coordinates
GRCh37:chrX:118967989-118986991
GRCh38:chrX:119805311-119853028
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

33.04

pLI (gnomAD)

0.98

LOEUF (gnomAD)

0.29

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive3 Supportive2 Moderate1 Strong1

Publications:

Ibarluzea N et. al., Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability., Genes (Basel), 2020
Soden SE et. al., Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders., Sci Transl Med, 2014
Iossifov I et. al., The contribution of de novo coding mutations to autism spectrum disorder., Nature, 2014
Lynch SA et. al., Broadening the phenotype associated with mutations in UPF3B: two further cases with renal dysplasia and variable developmental delay., Eur J Med Genet, 2012
Tarpey PS et. al., Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation., Nat Genet, 2007
Xu X et. al., Exome sequencing identifies UPF3B as the causative gene for a Chinese non-syndrome mental retardation pedigree., Clin Genet, 2013
Laumonnier F et. al., Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with nonspecific mental retardation with or without autism., Mol Psychiatry, 2010
Addington AM et. al., A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders., Mol Psychiatry, 2011
Chérot E et. al., Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients., Clin Genet, 2018
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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