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

Summary

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
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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).
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.
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.
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.
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.
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.
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.
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.
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

Go to the top of the page Help

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH12036 (e-PCR)
- UniSTS:26127

D8S2279 (e-PCR)
- UniSTS:473907

D13S116 (e-PCR)
- UniSTS:147007

RH102267 (e-PCR)
- UniSTS:96601

D7S3207 (e-PCR)
- UniSTS:229489

D1S1423 (e-PCR)
- UniSTS:149619

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

Go to the top of the page Help

Preferred Names: flap endonuclease GEN homolog 1

Names: Gen endonuclease homolog 1; Holliday junction resolvase

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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

NG_051292.2 RefSeqGene

Range

5862..40670

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

17753278..17788946

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q17RS7, Q17RS9, Q6ZN37
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
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
XM_047444156.1 → XP_047300112.1 flap endonuclease GEN homolog 1 isoform X2
XM_047444157.1 → XP_047300113.1 flap endonuclease GEN homolog 1 isoform X2
XM_047444155.1 → XP_047300111.1 flap endonuclease GEN homolog 1 isoform X2
XM_047444158.1 → XP_047300114.1 flap endonuclease GEN homolog 1 isoform X2
XM_047444159.1 → XP_047300115.1 flap endonuclease GEN homolog 1 isoform X2