UPF1

UPF1 RNA helicase and ATPase, the group of DECID complex|SURF complex|UPF1 like RNA helicases

Basic information

Region (hg38): 19:18831959-18868230

Previous symbols: [ "RENT1" ]

Links

ENSG00000005007NCBI:5976OMIM:601430HGNC:9962Uniprot:Q92900AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UPF1 gene.

  • not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UPF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
10
clinvar
5
clinvar
15
missense
1
clinvar
1
clinvar
59
clinvar
1
clinvar
1
clinvar
63
nonsense
0
start loss
0
frameshift
1
clinvar
1
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
1
2
3
non coding
15
clinvar
15
Total 1 1 61 11 21

Variants in UPF1

This is a list of pathogenic ClinVar variants found in the UPF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
19-18832079-C-G Benign (May 15, 2021)1228122
19-18832273-G-C Uncertain significance (Mar 09, 2023)2579588
19-18832300-T-A Uncertain significance (Jun 27, 2024)3392929
19-18832347-G-A Benign (Aug 28, 2019)1268198
19-18832349-C-T not specified Uncertain significance (Sep 22, 2022)2312754
19-18832363-G-A not specified Uncertain significance (May 18, 2022)2290202
19-18832367-G-C not specified Uncertain significance (Jul 22, 2024)3466242
19-18832400-G-T not specified Uncertain significance (Sep 24, 2024)3466245
19-18845890-G-A Benign (May 15, 2021)1263694
19-18845988-C-T Likely benign (Apr 01, 2023)2649593
19-18845989-G-A not specified Uncertain significance (Nov 26, 2024)3466247
19-18846006-C-T Likely benign (Dec 01, 2022)2649594
19-18846011-C-T not specified Uncertain significance (Aug 28, 2024)3466243
19-18846064-G-C Uncertain significance (Apr 28, 2022)1712749
19-18846082-A-G not specified Uncertain significance (Aug 30, 2022)2309709
19-18846088-T-C Uncertain significance (Aug 19, 2024)3764232
19-18846117-C-CA Uncertain significance (Apr 14, 2023)2663551
19-18847760-G-A not specified Uncertain significance (Jun 03, 2024)3331132
19-18847775-G-A not specified Uncertain significance (Jul 09, 2024)3466241
19-18850100-G-A Uncertain significance (Mar 27, 2023)2582044
19-18850160-T-C Uncertain significance (Jun 24, 2024)3392708
19-18850167-A-G Uncertain significance (May 12, 2022)1723589
19-18850212-A-G Uncertain significance (Oct 25, 2023)3363309
19-18850678-C-T Benign (Jan 02, 2019)711530
19-18850699-C-G Uncertain significance (Mar 26, 2023)2582021

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
UPF1protein_codingprotein_codingENST00000262803 2336299
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.009.24e-7125742061257480.0000239
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense5.632917140.4080.00004677305
Missense in Polyphen31199.670.155261916
Synonymous-0.5253373251.040.00002422226
Loss of Function6.46456.30.07100.00000250637

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002890.0000289
Ashkenazi Jewish0.000.00
East Asian0.00005630.0000544
Finnish0.00004620.0000462
European (Non-Finnish)0.00002660.0000264
Middle Eastern0.00005630.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: RNA-dependent helicase and ATPase required for nonsense- mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD. Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1- eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors. UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways. Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2. For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD. Essential for embryonic viability. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:21145460, ECO:0000269|PubMed:21419344}.;
Pathway
mRNA surveillance pathway - Homo sapiens (human);RNA transport - Homo sapiens (human);Metabolism of RNA;Nonsense-Mediated Decay (NMD);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (Consensus)

Recessive Scores

pRec
0.230

Intolerance Scores

loftool
0.0218
rvis_EVS
-1.53
rvis_percentile_EVS
3.39

Haploinsufficiency Scores

pHI
0.742
hipred
Y
hipred_score
0.825
ghis
0.604

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.859

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Upf1
Phenotype
cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; embryo phenotype;

Zebrafish Information Network

Gene name
upf1
Affected structure
whole organism
Phenotype tag
abnormal
Phenotype quality
decreased length

Gene ontology

Biological process
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay;nuclear-transcribed mRNA catabolic process;DNA replication;DNA repair;mRNA export from nucleus;regulation of translational termination;dosage compensation by inactivation of X chromosome;viral process;telomere maintenance via semi-conservative replication;regulation of telomere maintenance;cell cycle phase transition;positive regulation of mRNA catabolic process;3'-UTR-mediated mRNA destabilization;histone mRNA catabolic process;cellular response to lipopolysaccharide;cellular response to interleukin-1
Cellular component
nuclear chromosome, telomeric region;chromatin;P-body;nucleus;nucleoplasm;cytoplasm;cytosol;exon-exon junction complex;supraspliceosomal complex
Molecular function
chromatin binding;RNA binding;ATP-dependent RNA helicase activity;helicase activity;protein binding;ATP binding;zinc ion binding;telomeric DNA binding