UPF3A
protein-codingUPF3A regulator of nonsense mediated mRNA decay
Gene summary
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 13. Several splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UPF3A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_023011.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 100 | 2 | 102 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 102 | 2 | 0 | 104 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_075387.1 | 10 | MANE Select | |
| Ensembl | ENSP00000364448.3 | 10 | MANE Select | |
| RefSeq | NP_001340573.1 | 6 | Standard | |
| RefSeq | NP_001340574.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| upf3a | Danio rerio | Structure: brain morphogenesis Quality: process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA surveillance pathway - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
- Metabolism of RNA
- Nonsense-Mediated Decay (NMD)
- Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
Biological Process
- nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
- nucleocytoplasmic transport
- positive regulation of translation
- mRNA transport
Molecular Function
- RNA binding
- protein binding
- structural constituent of nuclear pore
- telomeric DNA binding
Cellular Component
- nucleus
- nucleolus
- cytoplasm
- cytosol
- exon-exon junction complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375299
- Coding exons
- 10
- Length
- 24225
- Individuals with no LoFs
- 125680
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125715
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.605 | 275 | 248 | 1.11 | 0.0000133 | 3042 |
| Missense (PolyPhen) | 54 | 63.329 | 0.85269 | 865 | ||
| Synonymous | -2.99 | 132 | 95.0 | 1.39 | 0.00000528 | 877 |
| Loss of Function | 1.76 | 13 | 21.9 | 0.594 | 0.00000107 | 305 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000060 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00034 | 0.00033 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00017 | 0.00016 | rare |
| South Asian | 0.00018 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. However, UPF3A is shown to be only marginally active in NMD as compared to UPF3B. Binds spliced mRNA upstream of exon-exon junctions. In vitro, weakly stimulates translation. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:16601204}.;
Recessive Scores
- pRec
- 0.0943
Intolerance Scores
- LoFtool
- 0.886
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.238
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |