This gene encodes a member of the Rad2/xeroderma pigmentosum group G nuclease family, whose members are characterized by N-terminal and internal xeroderma pigmentosum group G nuclease domains followed by helix-hairpin-helix domains and disordered C-terminal domains. The protein encoded by this gene is involved in resolution of Holliday junctions, which are intermediate four-way... See more...

Aliases for GEN1 Gene

Aliases for GEN1 Gene

  • GEN1 Holliday Junction 5' Flap Endonuclease 2 3 5
  • Flap Endonuclease GEN Homolog 1 3 4
  • Holliday Junction Resolvase 2 3
  • Gen Endonuclease Homolog 1 (Drosophila) 2
  • Gen Endonuclease Homolog 1 3
  • EC 3.1.-.- 4
  • Gen 3

External Ids for GEN1 Gene

Previous GeneCards Identifiers for GEN1 Gene

  • GC02P017798
  • GC02P017935

Summaries for GEN1 Gene

Entrez Gene Summary for GEN1 Gene

  • This gene encodes a member of the Rad2/xeroderma pigmentosum group G nuclease family, whose members are characterized by N-terminal and internal xeroderma pigmentosum group G nuclease domains followed by helix-hairpin-helix domains and disordered C-terminal domains. The protein encoded by this gene is involved in resolution of Holliday junctions, which are intermediate four-way structures that covalently link DNA during homologous recombination and double-strand break repair. The protein resolves Holliday junctions by creating dual incisions across the junction to produce nicked duplex products that can be ligated. In addition, this protein has been found to localize to centrosomes where it has been implicated in regulation of centrosome integrity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

GeneCards Summary for GEN1 Gene

GEN1 (GEN1 Holliday Junction 5' Flap Endonuclease) is a Protein Coding gene. Diseases associated with GEN1 include Cefaclor Allergy and Intracranial Abscess. Among its related pathways are Homologous DNA Pairing and Strand Exchange and DNA Double-Strand Break Repair. Gene Ontology (GO) annotations related to this gene include nuclease activity and crossover junction endodeoxyribonuclease activity. An important paralog of this gene is EXO1.

UniProtKB/Swiss-Prot Summary for GEN1 Gene

  • Endonuclease which resolves Holliday junctions (HJs) by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated. Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation (PubMed:19020614, PubMed:26682650). Cleaves HJs by a nick and counter-nick mechanism involving dual coordinated incisions that lead to the formation of ligatable nicked duplex products. Cleavage of the first strand is rate limiting, while second strand cleavage is rapid. Largely monomeric, dimerizes on the HJ and the first nick occurs upon dimerization at the junction (PubMed:26578604). Efficiently cleaves both single and double HJs contained within large recombination intermediates. Exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA (PubMed:28049850). Has also endonuclease activity on 5'-flap and replication fork (RF) DNA substrates (PubMed:26578604).

Additional gene information for GEN1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GEN1 Gene

Genomics for GEN1 Gene

GeneHancer (GH) Regulatory Elements for GEN1 Gene

Promoters and enhancers for GEN1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J017749 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 528.6 +0.6 639 8.6 FOXK2 HNRNPK ZBTB40 SIN3A NRF1 POLR2G NCOR1 GTF2E2 PHF8 ZFX GEN1 SMC6 HSALNG0013294 RF00104-013
GH02J017798 Enhancer 1 Ensembl ENCODE dbSUPER 28.8 +46.3 46329 3.4 SIN3A RELA RCOR1 TGIF2 TRIM22 MXI1 ZNF585B SAP130 CHD1 TBP SMC6 LOC105373449 lnc-RAD51AP2-1 GEN1 piR-61101-363
GH02J017803 Enhancer 0.9 ENCODE dbSUPER 27.8 +50.9 50921 1.7 EP300 RELA RCOR1 TRIM22 BCL11A MEF2B NBN SPI1 IRF4 POU2F2 GEN1 VSNL1 HSALNG0013300 LOC105373449
GH02J017811 Enhancer 1.1 Ensembl ENCODE dbSUPER 19.1 +60.6 60590 5.6 SP1 EP300 RELA MEF2C TRIM22 POLR2A BCL11A TCF12 CBFB ZNF384 GEN1 AB372692 MSGN1 HSALNG0013300
GH02J017821 Enhancer 1.2 Ensembl ENCODE CraniofacialAtlas dbSUPER 17.9 +68.9 68873 3.8 EP300 RELA TRIM22 MEF2B NBN SMARCA5 IKZF1 NR2F1 RCOR1 ATF2 GEN1 SMC6 MSGN1 piR-34822-168
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GEN1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GEN1

Top Transcription factor binding sites by QIAGEN in the GEN1 gene promoter:
  • AML1a
  • Pax-6
  • PPAR-alpha
  • S8
  • TBP
  • TFIID

Genomic Locations for GEN1 Gene

Genomic Locations for GEN1 Gene
chr2:17,753,627-17,788,946
(GRCh38/hg38)
Size:
35,320 bases
Orientation:
Plus strand
chr2:17,935,125-17,966,632
(GRCh37/hg19)
Size:
31,508 bases
Orientation:
Plus strand

Genomic View for GEN1 Gene

Genes around GEN1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GEN1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GEN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GEN1 Gene

Proteins for GEN1 Gene

  • Protein details for GEN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q17RS7-GEN_HUMAN
    Recommended name:
    Flap endonuclease GEN homolog 1
    Protein Accession:
    Q17RS7
    Secondary Accessions:
    • Q17RS9
    • Q6ZN37

    Protein attributes for GEN1 Gene

    Size:
    908 amino acids
    Molecular mass:
    102884 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Largely monomeric, dimerizes on the Holliday junction and the first nick occurs upon dimerization at the junction.

    Three dimensional structures from OCA and Proteopedia for GEN1 Gene

neXtProt entry for GEN1 Gene

Post-translational modifications for GEN1 Gene

  • Ubiquitination at Lys230
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for GEN1 Gene

Domains & Families for GEN1 Gene

Gene Families for GEN1 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for GEN1 Gene

Blocks:
  • Xeroderma pigmentosum group G/yeast RAD superfamily signature
  • Helix-hairpin-helix motif, class 2
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GEN1 Gene

GenScript: Design optimal peptide antigens:
  • Flap endonuclease GEN homolog 1 (GEN_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q17RS7

UniProtKB/Swiss-Prot:

GEN_HUMAN :
  • XPG-N, XPG-I,5'-3' exonuclease domains interact with DNA. Contains a chromodomain that acts as additional DNA interaction site and is required for efficient DNA recognition and cleavage.
  • Belongs to the XPG/RAD2 endonuclease family. GEN subfamily.
Domain:
  • XPG-N, XPG-I,5'-3' exonuclease domains interact with DNA. Contains a chromodomain that acts as additional DNA interaction site and is required for efficient DNA recognition and cleavage.
Family:
  • Belongs to the XPG/RAD2 endonuclease family. GEN subfamily.
genes like me logo Genes that share domains with GEN1: view

Function for GEN1 Gene

Molecular function for GEN1 Gene

UniProtKB/Swiss-Prot Function:
Endonuclease which resolves Holliday junctions (HJs) by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated. Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation (PubMed:19020614, PubMed:26682650). Cleaves HJs by a nick and counter-nick mechanism involving dual coordinated incisions that lead to the formation of ligatable nicked duplex products. Cleavage of the first strand is rate limiting, while second strand cleavage is rapid. Largely monomeric, dimerizes on the HJ and the first nick occurs upon dimerization at the junction (PubMed:26578604). Efficiently cleaves both single and double HJs contained within large recombination intermediates. Exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA (PubMed:28049850). Has also endonuclease activity on 5'-flap and replication fork (RF) DNA substrates (PubMed:26578604).

Enzyme Numbers (IUBMB) for GEN1 Gene

Phenotypes From GWAS Catalog for GEN1 Gene

Gene Ontology (GO) - Molecular Function for GEN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 26682650
GO:0000400 four-way junction DNA binding IBA,IDA 26578604
GO:0003677 DNA binding IEA --
GO:0003824 catalytic activity IEA --
GO:0004518 nuclease activity IEA --
genes like me logo Genes that share ontologies with GEN1: view
genes like me logo Genes that share phenotypes with GEN1: view

Animal Model Products

  • Taconic Biosciences Mouse Models for GEN1

CRISPR Products

miRNA for GEN1 Gene

miRTarBase miRNAs that target GEN1

Clone Products

  • Addgene plasmids for GEN1

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for GEN1 Gene

Localization for GEN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GEN1 Gene

Nucleus.

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 GEN1 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 3
plasma membrane 2
extracellular 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GEN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0005813 centrosome IDA 23166748
genes like me logo Genes that share ontologies with GEN1: view

Pathways & Interactions for GEN1 Gene

genes like me logo Genes that share pathways with GEN1: view

Gene Ontology (GO) - Biological Process for GEN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000724 double-strand break repair via homologous recombination IMP 23166748
GO:0006281 DNA repair IEA --
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0010824 regulation of centrosome duplication IMP 23108668
GO:0031297 replication fork processing IDA 26578604
genes like me logo Genes that share ontologies with GEN1: view

No data available for SIGNOR curated interactions for GEN1 Gene

Drugs & Compounds for GEN1 Gene

(1) Drugs for GEN1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved, Experimental, Investigational Pharma 0
genes like me logo Genes that share compounds with GEN1: view

Transcripts for GEN1 Gene

mRNA/cDNA for GEN1 Gene

2 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for GEN1

Alternative Splicing Database (ASD) splice patterns (SP) for GEN1 Gene

No ASD Table

Relevant External Links for GEN1 Gene

GeneLoc Exon Structure for
GEN1

Expression for GEN1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GEN1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for GEN1 Gene

This gene is overexpressed in Esophagus (56.1) and Salivary gland (12.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GEN1 Gene



Protein tissue co-expression partners for GEN1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GEN1

SOURCE GeneReport for Unigene cluster for GEN1 Gene:

Hs.467793

Evidence on tissue expression from TISSUES for GEN1 Gene

  • Nervous system(4.1)
genes like me logo Genes that share expression patterns with GEN1: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GEN1 Gene

Orthologs for GEN1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GEN1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GEN1 31 30
  • 99.6 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GEN1 31 30
  • 86.59 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GEN1 31 30
  • 85.03 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gen1 30
  • 79.86 (n)
mouse
(Mus musculus)
Mammalia Gen1 17 31 30
  • 79.15 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia GEN1 31
  • 45 (a)
OneToOne
chicken
(Gallus gallus)
Aves GEN1 31 30
  • 58.58 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GEN1 31
  • 41 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii GEN1 31
  • 26 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Gen 31
  • 24 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea crn-1 31
  • 23 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RAD27 31
  • 21 (a)
OneToMany
YEN1 33
thale cress
(Arabidopsis thaliana)
eudicotyledons AT1G01880 30
  • 46.79 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 45 (a)
OneToOne
Species where no ortholog for GEN1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • 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)
  • oppossum (Monodelphis domestica)
  • 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 urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for GEN1 Gene

ENSEMBL:
Gene Tree for GEN1 (if available)
TreeFam:
Gene Tree for GEN1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GEN1: view image

Paralogs for GEN1 Gene

Paralogs for GEN1 Gene

(2) SIMAP similar genes for GEN1 Gene using alignment to 4 proteins:

  • GEN_HUMAN
  • E9PLG0_HUMAN
  • E9PM30_HUMAN
  • H0YCG6_HUMAN
genes like me logo Genes that share paralogs with GEN1: view

Variants for GEN1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GEN1 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs144389157 Likely Benign: Hereditary cancer-predisposing syndrome 17,757,644(+) A/T INTRON_VARIANT
rs145421265 Likely Benign: Hereditary cancer-predisposing syndrome 17,774,596(+) A/G INTRON_VARIANT
rs186660424 Likely Benign: Hereditary cancer-predisposing syndrome 17,771,175(+) A/T INTRON_VARIANT
rs190514572 Likely Benign: Hereditary cancer-predisposing syndrome 17,758,468(+) T/C INTRON_VARIANT
rs191898243 Likely Benign: Hereditary cancer-predisposing syndrome 17,771,098(+) G/A INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for GEN1 Gene

Structural Variations from Database of Genomic Variants (DGV) for GEN1 Gene

Variant ID Type Subtype PubMed ID
dgv1872n106 CNV deletion 24896259
esv2061440 CNV deletion 18987734
esv2719750 CNV deletion 23290073
esv2759031 CNV gain 17122850
esv3589949 CNV gain 21293372
esv3891603 CNV gain 25118596
nsv1135080 CNV deletion 24896259
nsv522195 CNV loss 19592680
nsv997502 CNV gain 25217958

Variation tolerance for GEN1 Gene

Residual Variation Intolerance Score: 65.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.69; 82.96% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GEN1 Gene

Human Gene Mutation Database (HGMD)
GEN1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GEN1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GEN1 Gene

Disorders for GEN1 Gene

MalaCards: The human disease database

(8) MalaCards diseases for GEN1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
cefaclor allergy
  • ceclor allergy
intracranial abscess
xeroderma pigmentosum, complementation group g
  • xpg
chronic purulent otitis media
  • chronic suppurative otitis media
external ear disease
  • preauricular cyst
- elite association - COSMIC cancer census association via MalaCards
Search GEN1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GEN1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GEN1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GEN1 Gene

Publications for GEN1 Gene

  1. Resolution of single and double Holliday junction recombination intermediates by GEN1. (PMID: 28049850) Shah Punatar R … West SC (Proceedings of the National Academy of Sciences of the United States of America 2017) 3 4 54
  2. GEN1 promotes Holliday junction resolution by a coordinated nick and counter-nick mechanism. (PMID: 26578604) Chan YW … West S (Nucleic acids research 2015) 3 4 54
  3. Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage. (PMID: 26682650) Lee SH … Biertümpfel C (eLife 2015) 3 4 54
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  5. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PMID: 20800603) Flachsbart F … Nebel A (Mutation research 2010) 3 41 54

Products for GEN1 Gene

Sources for GEN1 Gene