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GEN1 GEN1 Holliday junction 5' flap endonuclease [ Homo sapiens (human) ]

Gene ID: 348654, updated on 27-Nov-2024

Summary

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Official Symbol
GEN1provided by HGNC
Official Full Name
GEN1 Holliday junction 5' flap endonucleaseprovided by HGNC
Primary source
HGNC:HGNC:26881
See related
Ensembl:ENSG00000178295 MIM:612449; AllianceGenome:HGNC:26881
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
Gen
Summary
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]
Expression
Broad expression in lymph node (RPKM 4.2), testis (RPKM 3.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See GEN1 in Genome Data Viewer
Location:
2p24.2
Exon count:
19
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (17753278..17788946)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (17785078..17820679)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (17935136..17970213)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene nascent polypeptide associated complex subunit alpha pseudogene Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:17699235-17700434 Neighboring gene RAD51 associated protein 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15351 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:17724689-17725200 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:17725201-17725712 Neighboring gene visinin like 1 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr2:17760843-17761612 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:17771124-17772061 Neighboring gene uncharacterized LOC124908054 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:17825464-17826251 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15352 Neighboring gene structural maintenance of chromosomes 6 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:17929152-17929835 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11189 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11190 Neighboring gene uncharacterized LOC105373449 Neighboring gene Sharpr-MPRA regulatory region 14936 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15353 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15354 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15355 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15356 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:18008377-18009074 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:18011228-18011728 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11191 Neighboring gene uncharacterized LOC112267888 Neighboring gene mesogenin 1 Neighboring gene zona pellucida glycoprotein AX, pseudogene

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. GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract. Du X, et al. Hum Genomics, 2024 Apr 24. PMID 38654324, Free PMC Article
  2. Reverse Transcription-PCR-based Sanger Sequencing-confirmed Exon-skipping Effect of a Novel GEN1 Intronic Variant (c.1408+4A>G). Kim J, et al. Ann Lab Med, 2024 Mar 1. PMID 37840312, Free PMC Article
  3. The human Holliday junction resolvase GEN1 rescues the meiotic phenotype of a Schizosaccharomyces pombe mus81 mutant. Lorenz A, et al. Nucleic Acids Res, 2010 Apr. PMID 20040574, Free PMC Article
  4. Mutation and association analysis of GEN1 in breast cancer susceptibility. Turnbull C, et al. Breast Cancer Res Treat, 2010 Nov. PMID 20512659, Free PMC Article
  5. Mechanism of Holliday junction resolution by the human GEN1 protein. Rass U, et al. Genes Dev, 2010 Jul 15. PMID 20634321, Free PMC Article

See all (51) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.
    Title: GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.
  2. Reverse Transcription-PCR-based Sanger Sequencing-confirmed Exon-skipping Effect of a Novel GEN1 Intronic Variant (c.1408+4A>G).
    Title: Reverse Transcription-PCR-based Sanger Sequencing-confirmed Exon-skipping Effect of a Novel GEN1 Intronic Variant (c.1408+4A>G).
  3. NCAPH Stabilizes GEN1 in Chromatin to Resolve Ultra-Fine DNA Bridges and Maintain Chromosome Stability.
    Title: NCAPH Stabilizes GEN1 in Chromatin to Resolve Ultra-Fine DNA Bridges and Maintain Chromosome Stability.
  4. The tight binding of GEN1 monomer to intact- and singly-cleaved Holliday junctions empowers it as the last resort to process Holliday junctions that escape the primary mechanisms
    Title: Resolution of the Holliday junction recombination intermediate by human GEN1 at the single-molecule level.
  5. Using RNAi or FA-P cells complemented with SLX4 mutants that abrogate interaction with MUS81 or SLX1, we show that SLX4 cooperates with MUS81 to introduce DSBs after replication stress but also counteracts pathological targeting of demised forks by GEN1.
    Title: SLX4 Prevents GEN1-Dependent DSBs During DNA Replication Arrest Under Pathological Conditions in Human Cells.
  6. GEN1 efficiently cleaves both single and double Holliday junctions contained within large recombination intermediates. Moreover, we find that GEN1 exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA.
    Title: Resolution of single and double Holliday junction recombination intermediates by GEN1.
  7. the in vitro activities of DmGen and HsGEN1 are strikingly similar.
    Title: Substrate preference of Gen endonucleases highlights the importance of branched structures as DNA damage repair intermediates.
  8. Data suggest that dimeric GEN1 binds with high affinity/selectivity to Holliday junctions, introducing two symmetrical hydrolytic cleavages of phosphodiester backbone; at present, less is known about SLX1-SLX4-MUS81-EME1 resolving enzyme complex. (GEN1 = Holliday junction 5' flap endonuclease; SLX = structure-specific endonuclease subunit; MUS81 = MUS81 endonuclease; EME1 = essential meiotic endonuclease 1) [REVIEW]
    Title: Holliday junction-resolving enzymes-structures and mechanisms.
  9. human GEN1 protein promotes Holliday junction resolution by a mechanism that is analogous to that exhibited by the prototypic HJ resolvase E. coli RuvC.
    Title: GEN1 promotes Holliday junction resolution by a coordinated nick and counter-nick mechanism.
  10. GEN1 is controlled by nuclear exclusion, driven by a nuclear export signal that restricts GEN1 actions to mitosis. Spatial control of GEN1 contributes to genome stability by avoiding competition with non-crossover promoting repair pathways.
    Title: Spatial control of the GEN1 Holliday junction resolvase ensures genome stability.
Submit: New GeneRIF Correction See all GeneRIFs (21)

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

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2021-02-02)

ClinGen Genome Curation Page
Haploinsufficency

Dosage sensitivity unlikely (Last evaluated 2021-02-02)

ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ36312, FLJ40869, DKFZp781F0986

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 5'-flap endonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 5'-flap endonuclease activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables crossover junction DNA endonuclease activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables crossover junction DNA endonuclease activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables four-way junction DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables four-way junction DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in double-strand break repair via homologous recombination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of mitotic cell cycle spindle assembly checkpoint IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of centrosome duplication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in replication fork processing IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in resolution of DNA recombination intermediates IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in resolution of mitotic recombination intermediates IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
flap endonuclease GEN homolog 1
Names
Gen endonuclease homolog 1
Holliday junction resolvase

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.

Genomic

  1. NG_051292.2 RefSeqGene

    Range
    5862..40670
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001130009.3 → NP_001123481.3  flap endonuclease GEN homolog 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC093731, AC097377
    Consensus CDS
    CCDS1691.1
    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37
    Related
    ENSP00000370653.2, ENST00000381254.7
    Conserved Domains (3) summary
    cd09905
    Location:195 → 338
    H3TH_GEN1; H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease
    cd09869
    Location:2 → 206
    PIN_GEN1; FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs
    pfam18704
    Location:398 → 458
    Chromo_2; Chromatin organization modifier domain 2

  2. NM_182625.5 → NP_872431.5  flap endonuclease GEN homolog 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shorter transcript. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC093731, AC097377
    Consensus CDS
    CCDS1691.1
    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37
    Related
    ENSP00000318977.7, ENST00000317402.11
    Conserved Domains (3) summary
    cd09905
    Location:195 → 338
    H3TH_GEN1; H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease
    cd09869
    Location:2 → 206
    PIN_GEN1; FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs
    pfam18704
    Location:398 → 458
    Chromo_2; Chromatin organization modifier domain 2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    17753278..17788946
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011532822.3 → XP_011531124.1  flap endonuclease GEN homolog 1 isoform X1

    See identical proteins and their annotated locations for XP_011531124.1

    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37
    Conserved Domains (3) summary
    cd09905
    Location:195 → 338
    H3TH_GEN1; H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease
    cd09869
    Location:2 → 206
    PIN_GEN1; FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs
    pfam18704
    Location:398 → 458
    Chromo_2; Chromatin organization modifier domain 2

  2. XM_011532820.3 → XP_011531122.1  flap endonuclease GEN homolog 1 isoform X1

    See identical proteins and their annotated locations for XP_011531122.1

    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37
    Conserved Domains (3) summary
    cd09905
    Location:195 → 338
    H3TH_GEN1; H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease
    cd09869
    Location:2 → 206
    PIN_GEN1; FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs
    pfam18704
    Location:398 → 458
    Chromo_2; Chromatin organization modifier domain 2

  3. XM_006712005.4 → XP_006712068.1  flap endonuclease GEN homolog 1 isoform X1

    See identical proteins and their annotated locations for XP_006712068.1

    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37
    Conserved Domains (3) summary
    cd09905
    Location:195 → 338
    H3TH_GEN1; H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease
    cd09869
    Location:2 → 206
    PIN_GEN1; FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs
    pfam18704
    Location:398 → 458
    Chromo_2; Chromatin organization modifier domain 2

  4. XM_047444147.1 → XP_047300103.1  flap endonuclease GEN homolog 1 isoform X1

    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37

  5. XM_011532821.3 → XP_011531123.1  flap endonuclease GEN homolog 1 isoform X1

    See identical proteins and their annotated locations for XP_011531123.1

    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37
    Conserved Domains (3) summary
    cd09905
    Location:195 → 338
    H3TH_GEN1; H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease
    cd09869
    Location:2 → 206
    PIN_GEN1; FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs
    pfam18704
    Location:398 → 458
    Chromo_2; Chromatin organization modifier domain 2

  6. XM_005262613.5 → XP_005262670.1  flap endonuclease GEN homolog 1 isoform X1

    See identical proteins and their annotated locations for XP_005262670.1

    UniProtKB/Swiss-Prot
    Q17RS7, Q17RS9, Q6ZN37
    Conserved Domains (3) summary
    cd09905
    Location:195 → 338
    H3TH_GEN1; H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease
    cd09869
    Location:2 → 206
    PIN_GEN1; FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs
    pfam18704
    Location:398 → 458
    Chromo_2; Chromatin organization modifier domain 2

  7. XM_047444156.1 → XP_047300112.1  flap endonuclease GEN homolog 1 isoform X2

  8. XM_047444157.1 → XP_047300113.1  flap endonuclease GEN homolog 1 isoform X2

  9. XM_047444155.1 → XP_047300111.1  flap endonuclease GEN homolog 1 isoform X2

  10. XM_047444158.1 → XP_047300114.1  flap endonuclease GEN homolog 1 isoform X2

  11. XM_047444159.1 → XP_047300115.1  flap endonuclease GEN homolog 1 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    17785078..17820679
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341774.1 → XP_054197749.1  flap endonuclease GEN homolog 1 isoform X1

  2. XM_054341770.1 → XP_054197745.1  flap endonuclease GEN homolog 1 isoform X1

  3. XM_054341772.1 → XP_054197747.1  flap endonuclease GEN homolog 1 isoform X1

  4. XM_054341775.1 → XP_054197750.1  flap endonuclease GEN homolog 1 isoform X1

  5. XM_054341771.1 → XP_054197746.1  flap endonuclease GEN homolog 1 isoform X1

  6. XM_054341773.1 → XP_054197748.1  flap endonuclease GEN homolog 1 isoform X1

  7. XM_054341777.1 → XP_054197752.1  flap endonuclease GEN homolog 1 isoform X2

  8. XM_054341778.1 → XP_054197753.1  flap endonuclease GEN homolog 1 isoform X2

  9. XM_054341776.1 → XP_054197751.1  flap endonuclease GEN homolog 1 isoform X2

  10. XM_054341779.1 → XP_054197754.1  flap endonuclease GEN homolog 1 isoform X2

  11. XM_054341780.1 → XP_054197755.1  flap endonuclease GEN homolog 1 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q17RS7.2 GenPept UniProtKB/Swiss-Prot:Q17RS7

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