This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010] See more...

Aliases for RIF1 Gene

Aliases for RIF1 Gene

  • Replication Timing Regulatory Factor 1 2 3 5
  • Rap1-Interacting Factor 1 Homolog 3 4
  • Telomere-Associated Protein RIF1 3 4
  • RAP1 Interacting Factor Homolog (Yeast) 2
  • RAP1 Interacting Factor Homolog 3
  • FLJ12870 2
  • FLJ10599 2
  • RIF1 5

External Ids for RIF1 Gene

Previous GeneCards Identifiers for RIF1 Gene

  • GC01M110591
  • GC01M110788
  • GC01M111201
  • GC02P152093
  • GC02P151974
  • GC02P152266
  • GC02P144162

Summaries for RIF1 Gene

Entrez Gene Summary for RIF1 Gene

  • This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

GeneCards Summary for RIF1 Gene

RIF1 (Replication Timing Regulatory Factor 1) is a Protein Coding gene. Diseases associated with RIF1 include Nemaline Myopathy 2 and Candida Glabrata. Among its related pathways are DNA Double-Strand Break Repair and Transcriptional Regulatory Network in Embryonic Stem Cell. Gene Ontology (GO) annotations related to this gene include binding.

UniProtKB/Swiss-Prot Summary for RIF1 Gene

  • Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity).

Gene Wiki entry for RIF1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RIF1 Gene

Genomics for RIF1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RIF1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RIF1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RIF1

Top Transcription factor binding sites by QIAGEN in the RIF1 gene promoter:
  • ATF-2
  • CRE-BP1
  • CREB
  • CUTL1
  • deltaCREB
  • HFH-1
  • p53
  • TBP
  • TFIID
  • YY1

Genomic Locations for RIF1 Gene

Latest Assembly
chr2:151,409,883-151,534,200
(GRCh38/hg38)
Size:
124,318 bases
Orientation:
Plus strand

Previous Assembly
chr2:152,266,416-152,338,686
(GRCh37/hg19 by Entrez Gene)
Size:
72,271 bases
Orientation:
Plus strand

chr2:152,266,397-152,364,527
(GRCh37/hg19 by Ensembl)
Size:
98,131 bases
Orientation:
Plus strand

Genomic View for RIF1 Gene

Genes around RIF1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RIF1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RIF1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RIF1 Gene

Proteins for RIF1 Gene

  • Protein details for RIF1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5UIP0-RIF1_HUMAN
    Recommended name:
    Telomere-associated protein RIF1
    Protein Accession:
    Q5UIP0
    Secondary Accessions:
    • A6NC27
    • C9JBR1
    • Q5H9R3
    • Q5UIP2
    • Q66YK6
    • Q6PRU2
    • Q8TE94
    • Q99772
    • Q9H830
    • Q9H9B9
    • Q9NVP5
    • Q9Y4R4

    Protein attributes for RIF1 Gene

    Size:
    2472 amino acids
    Molecular mass:
    274466 Da
    Quaternary structure:
    • Interacts with TP53BP1 (when phosphorylated by ATM) (PubMed:23333306, PubMed:28241136). May interact with TRF2 (By similarity). Interacts with SHLD2 (PubMed:29789392). Interacts with ERCC6 (via WHD region) (PubMed:29203878).
    SequenceCaution:
    • Sequence=BAA91705.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB14313.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB14792.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB85058.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAI45961.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for RIF1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RIF1 Gene

Post-translational modifications for RIF1 Gene

  • Glycosylation at Asn105
  • Ubiquitination at Lys125, Lys198, Lys251, Lys702, and Lys2328
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

No data available for DME Specific Peptides for RIF1 Gene

Domains & Families for RIF1 Gene

Gene Families for RIF1 Gene

Protein Domains for RIF1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for RIF1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ60845, highly similar to Telomere-associated protein RIF1 (B4DS49_HUMAN)
  • Rap1-interacting factor 1 homolog (RIF1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q5UIP0

UniProtKB/Swiss-Prot:

RIF1_HUMAN :
  • Belongs to the RIF1 family.
Family:
  • Belongs to the RIF1 family.
genes like me logo Genes that share domains with RIF1: view

Function for RIF1 Gene

Molecular function for RIF1 Gene

UniProtKB/Swiss-Prot Function:
Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity).

Phenotypes From GWAS Catalog for RIF1 Gene

Gene Ontology (GO) - Molecular Function for RIF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 22321011
genes like me logo Genes that share ontologies with RIF1: view
genes like me logo Genes that share phenotypes with RIF1: view

Animal Models for RIF1 Gene

MGI Knock Outs for RIF1:
  • Rif1 Rif1<tm2Sbcb>

miRNA for RIF1 Gene

miRTarBase miRNAs that target RIF1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RIF1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RIF1 Gene

Localization for RIF1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RIF1 Gene

Nucleus. Chromosome. Chromosome, telomere. Cytoplasm, cytoskeleton, spindle. Note=Following interaction with TP53BP1, recruited to sites of DNA damage, such as DSBs (By similarity). Exhibits ATM- and TP53BP1-dependent localization to uncapped or aberrant telomeres and to DNA double strand breaks (DSBs) (PubMed:15342490). Does not associate with normal telomere structures (PubMed:15342490, PubMed:15583028). Localizes to microtubules of the midzone of the mitotic spindle during anaphase, and to condensed chromosomes in telophase (PubMed:15583028). {ECO:0000250 UniProtKB:Q6PR54, ECO:0000269 PubMed:15342490, ECO:0000269 PubMed:15583028}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RIF1 gene
Compartment Confidence
plasma membrane 4
cytoskeleton 4
nucleus 4
mitochondrion 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
  • Nucleoplasm (3)
  • Plasma membrane (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RIF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000781 chromosome, telomeric region IEA --
GO:0000785 chromatin ISS --
GO:0000793 condensed chromosome IDA 15583028
GO:0001939 female pronucleus IEA --
GO:0001940 male pronucleus IEA --
genes like me logo Genes that share ontologies with RIF1: view

Pathways & Interactions for RIF1 Gene

genes like me logo Genes that share pathways with RIF1: view

Pathways by source for RIF1 Gene

1 Qiagen pathway for RIF1 Gene
  • Transcriptional Regulatory Network in Embryonic Stem Cell
1 Cell Signaling Technology pathway for RIF1 Gene

SIGNOR curated interactions for RIF1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for RIF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II ISS --
GO:0000723 telomere maintenance ISS --
GO:0006281 DNA repair IEA --
GO:0006303 double-strand break repair via nonhomologous end joining TAS --
GO:0006348 chromatin silencing at telomere ISS --
genes like me logo Genes that share ontologies with RIF1: view

Drugs & Compounds for RIF1 Gene

No Compound Related Data Available

Transcripts for RIF1 Gene

mRNA/cDNA for RIF1 Gene

4 REFSEQ mRNAs :
20 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RIF1

Alternative Splicing Database (ASD) splice patterns (SP) for RIF1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22a · 22b ^
SP1: - -
SP2:
SP3:
SP4:
SP5:

ExUns: 23 ^ 24 ^ 25 ^ 26 ^ 27 ^ 28a · 28b
SP1:
SP2:
SP3: -
SP4:
SP5:

Relevant External Links for RIF1 Gene

GeneLoc Exon Structure for
RIF1

Expression for RIF1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RIF1 Gene

Protein differential expression in normal tissues from HIPED for RIF1 Gene

This gene is overexpressed in Nasal epithelium (41.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for RIF1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RIF1

SOURCE GeneReport for Unigene cluster for RIF1 Gene:

Hs.655671

mRNA Expression by UniProt/SwissProt for RIF1 Gene:

Q5UIP0-RIF1_HUMAN
Tissue specificity: Highly expressed in testis.

Evidence on tissue expression from TISSUES for RIF1 Gene

  • Nervous system(4.6)
  • Liver(4.3)
genes like me logo Genes that share expression patterns with RIF1: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for RIF1 Gene

Orthologs for RIF1 Gene

This gene was present in the common ancestor of animals.

Orthologs for RIF1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RIF1 30 31
  • 99.45 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RIF1 30 31
  • 86.16 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RIF1 30 31
  • 86.12 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Rif1 30 17 31
  • 79.99 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rif1 30
  • 79.61 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 73 (a)
OneToMany
-- 31
  • 54 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia RIF1 31
  • 60 (a)
OneToOne
Chicken
(Gallus gallus)
Aves RIF1 30 31
  • 64.07 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RIF1 31
  • 47 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii rif1 31
  • 38 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG30085 31
  • 21 (a)
OneToOne
Species where no ortholog for RIF1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for RIF1 Gene

ENSEMBL:
Gene Tree for RIF1 (if available)
TreeFam:
Gene Tree for RIF1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RIF1: view image

Paralogs for RIF1 Gene

No data available for Paralogs for RIF1 Gene

Variants for RIF1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RIF1 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
533984 Uncertain Significance: Nemaline myopathy 2 151,531,039(+) TG/CA
NM_001271208.2(NEB):c.21689_21690inv (p.Thr7230Met)
MISSENSE
571908 Uncertain Significance: Nemaline myopathy 2 151,490,465(+) TG/CA
NM_001271208.2(NEB):c.25308_25309inv (p.Ile8437Val)
MISSENSE
834459 Uncertain Significance: Nemaline myopathy 2 151,525,262(+) T/A
NM_001271208.2(NEB):c.22278A>T (p.Lys7426Asn)
MISSENSE
835709 Pathogenic: Nemaline myopathy 2 151,524,371(+) T/TA
NM_001271208.2(NEB):c.22523dup (p.Leu7508fs)
FRAMESHIFT
836697 Uncertain Significance: Nemaline myopathy 2 151,526,028(+) C/T
NM_001271208.2(NEB):c.22196G>A (p.Gly7399Asp)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RIF1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RIF1 Gene

Variant ID Type Subtype PubMed ID
dgv4094n100 CNV gain 25217958
esv2467988 CNV deletion 19546169
esv34659 CNV loss 17911159
nsv1012891 CNV gain 25217958
nsv437298 CNV loss 16327808
nsv438374 CNV loss 16468122
nsv834418 CNV gain 17160897

Variation tolerance for RIF1 Gene

Residual Variation Intolerance Score: 19.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.43; 63.93% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RIF1 Gene

Human Gene Mutation Database (HGMD)
RIF1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RIF1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RIF1 Gene

Disorders for RIF1 Gene

MalaCards: The human disease database

(3) MalaCards diseases for RIF1 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
nemaline myopathy 2
  • nem2
candida glabrata
duane-radial ray syndrome
  • drrs
- elite association - COSMIC cancer census association via MalaCards
Search RIF1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for RIF1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with RIF1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RIF1 Gene

Publications for RIF1 Gene

  1. Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint. (PMID: 15342490) Silverman J … de Lange T (Genes & development 2004) 2 3 4 23
  2. Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules. (PMID: 15583028) Xu L … Blackburn EH (The Journal of cell biology 2004) 3 4 23
  3. FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells. (PMID: 29789392) Tomida J … Wood RD (The EMBO journal 2018) 3 4
  4. ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice. (PMID: 29203878) Batenburg NL … Zhu XD (Nature communications 2017) 3 4
  5. TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. (PMID: 28241136) Drané P … Chowdhury D (Nature 2017) 3 4

Products for RIF1 Gene

Sources for RIF1 Gene