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SHFL shiftless antiviral inhibitor of ribosomal frameshifting [ Homo sapiens (human) ]

Gene ID: 55337, updated on 5-Mar-2024

Summary

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Official Symbol
SHFLprovided by HGNC
Official Full Name
shiftless antiviral inhibitor of ribosomal frameshiftingprovided by HGNC
Primary source
HGNC:HGNC:25649
See related
Ensembl:ENSG00000130813 MIM:616808; AllianceGenome:HGNC:25649
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SFL; IRAV; RyDEN; C19orf66
Summary
This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression
Ubiquitous expression in liver (RPKM 17.9), spleen (RPKM 17.5) and 25 other tissues See more
Orthologs
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Genomic context

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See SHFL in Genome Data Viewer
Location:
19p13.2
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (10086317..10093243)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (10212537..10219461)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (10196993..10203919)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene microRNA 5589 Neighboring gene complement component 3 precursor pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr19:10185500-10185601 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10051 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10052 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10053 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10054 Neighboring gene angiopoietin like 6 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10055 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13936 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13937 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:10216675-10217318 Neighboring gene PPAN-P2RY11 readthrough Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10218607-10219250 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10220162-10220743 Neighboring gene small nucleolar RNA, C/D box 105 Neighboring gene small nucleolar RNA, C/D box 105B Neighboring gene peter pan homolog

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan. Liu N, et al. Front Cell Infect Microbiol, 2023. PMID 37293200, Free PMC Article
  2. Shiftless Restricts Viral Gene Expression and Influences RNA Granule Formation during Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication. Rodriguez W, et al. J Virol, 2022 Nov 23. PMID 36326276, Free PMC Article
  3. C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein. Yu D, et al. Virol Sin, 2021 Dec. PMID 34309824, Free PMC Article
  4. Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless. Napthine S, et al. Viruses, 2021 Jun 25. PMID 34202160, Free PMC Article
  5. The SARS-CoV-2 RNA-protein interactome in infected human cells. Schmidt N, et al. Nat Microbiol, 2021 Mar. PMID 33349665, Free PMC Article

See all (30) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genetic polymorphisms in the C19orf66 gene influenced HIV-1 infection in a Yunnan population.
    Title: Genetic polymorphisms in the C19orf66 gene influenced HIV-1 infection in a Yunnan population.
  2. Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan.
    Title: Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan.
  3. Shiftless Restricts Viral Gene Expression and Influences RNA Granule Formation during Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.
    Title: Shiftless Restricts Viral Gene Expression and Influences RNA Granule Formation during Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.
  4. C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein.
    Title: C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein.
  5. C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle.
    Title: C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle.
  6. Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless.
    Title: Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless.
  7. Taken together, this study identified C19orf66 as a novel interferon-stimulated gene that exerts antiviral effects against Zika virus by specifically degrading th viral NS3 nonstructural protein.
    Title: C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3.
  8. IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA.
    Title: IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10.
  9. we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits Dengue virus replication
    Title: Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ11286, FLJ40743

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ribosome binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ribosome binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables sequence-specific mRNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables sequence-specific mRNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in defense response to virus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in defense response to virus IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in innate immune response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of translational frameshifting IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of viral genome replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of translational termination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to interferon-beta IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to type I interferon IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to type II interferon IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to type III interferon IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in viral translational frameshifting IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in viral translational frameshifting IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in P-body IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
shiftless antiviral inhibitor of ribosomal frameshifting protein
Names
Repressor of yield of Dengue virus
UPF0515 protein C19orf66
interferon-regulated antiviral protein
repressor of yield of DENV protein
shiftless

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001308277.2 → NP_001295206.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform 2

    See identical proteins and their annotated locations for NP_001295206.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    BC026180, BC035817, DB481173
    Consensus CDS
    CCDS77231.1
    UniProtKB/Swiss-Prot
    Q9NUL5
    Related
    ENSP00000467182.1, ENST00000591813.5
    Conserved Domains (1) summary
    pfam15135
    Location:16 → 232
    UPF0515; Uncharacterized protein UPF0515

  2. NM_018381.4 → NP_060851.2  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform 1

    See identical proteins and their annotated locations for NP_060851.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AK002148, BC010847, DB481173
    Consensus CDS
    CCDS45957.1
    UniProtKB/Swiss-Prot
    A8MQT9, Q4G188, Q8IYH6, Q8N8V1, Q9NUL5
    Related
    ENSP00000253110.10, ENST00000253110.16
    Conserved Domains (1) summary
    pfam15135
    Location:16 → 268
    UPF0515; Uncharacterized protein UPF0515

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    10086317..10093243
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047439048.1 → XP_047295004.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X3

  2. XM_011528122.2 → XP_011526424.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X4

    Conserved Domains (1) summary
    pfam15135
    Location:16 → 78
    UPF0515; Uncharacterized protein UPF0515

  3. XM_047439046.1 → XP_047295002.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X1

  4. XM_047439047.1 → XP_047295003.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X2

    Related
    ENSP00000380978.3, ENST00000397881.7

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    10212537..10219461
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321378.1 → XP_054177353.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X3

  2. XM_054321379.1 → XP_054177354.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X4

  3. XM_054321376.1 → XP_054177351.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X1

  4. XM_054321377.1 → XP_054177352.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NUL5.2 GenPept UniProtKB/Swiss-Prot:Q9NUL5

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