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

ENSG00000005007 ∙ NCBI:5976 ∙ OMIM:601430 ∙ HGNC:9962 ∙ Uniprot:Q92900 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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	5	15
missense	1	1	59	1	1	63
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	2		3
non coding					15	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)
19-18832273-G-C			Uncertain significance (Mar 09, 2023)
19-18832300-T-A			Uncertain significance (Jun 27, 2024)
19-18832347-G-A			Benign (Aug 28, 2019)
19-18832349-C-T		not specified	Uncertain significance (Sep 22, 2022)
19-18832363-G-A		not specified	Uncertain significance (May 18, 2022)
19-18832367-G-C		not specified	Uncertain significance (Jul 22, 2024)
19-18832397-G-A		not specified	Uncertain significance (Dec 14, 2024)
19-18832400-G-T		not specified	Uncertain significance (Sep 24, 2024)
19-18845890-G-A			Benign (May 15, 2021)
19-18845988-C-T			Likely benign (Apr 01, 2023)
19-18845989-G-A		not specified	Uncertain significance (Nov 26, 2024)
19-18846006-C-T			Likely benign (Dec 01, 2022)
19-18846011-C-T		not specified	Uncertain significance (Aug 28, 2024)
19-18846064-G-C			Uncertain significance (Apr 28, 2022)
19-18846082-A-G		not specified	Uncertain significance (Aug 30, 2022)
19-18846088-T-C			Uncertain significance (Aug 19, 2024)
19-18846117-C-CA			Uncertain significance (Apr 14, 2023)
19-18847760-G-A		not specified	Uncertain significance (Jun 03, 2024)
19-18847775-G-A		not specified	Uncertain significance (Jul 09, 2024)
19-18850100-G-A			Uncertain significance (Mar 27, 2023)
19-18850160-T-C			Uncertain significance (Jun 24, 2024)
19-18850167-A-G			Uncertain significance (May 12, 2022)
19-18850212-A-G			Uncertain significance (Oct 25, 2023)
19-18850678-C-T			Benign (Jan 02, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UPF1	protein_coding	protein_coding	ENST00000262803	23	36299

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	9.24e-7	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.63	291	714	0.408	0.0000467	7305
Missense in Polyphen		31	199.67	0.15526		1916
Synonymous	-0.525	337	325	1.04	0.0000242	2226
Loss of Function	6.46	4	56.3	0.0710	0.00000250	637

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000563	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.0000563	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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