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POLE DNA polymerase epsilon, catalytic subunit [ Homo sapiens (human) ]

Gene ID: 5426, updated on 3-Nov-2024

Summary

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Official Symbol
POLEprovided by HGNC
Official Full Name
DNA polymerase epsilon, catalytic subunitprovided by HGNC
Primary source
HGNC:HGNC:9177
See related
Ensembl:ENSG00000177084 MIM:174762; AllianceGenome:HGNC:9177
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
FILS; POLE1; CRCS12; IMAGEI
Summary
This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]
Expression
Broad expression in bone marrow (RPKM 12.9), testis (RPKM 10.8) and 24 other tissues See more
Orthologs
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Genomic context

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See POLE in Genome Data Viewer
Location:
12q24.33
Exon count:
52
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (132623762..132687342, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (132673921..132737569, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (133200348..133263928, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:133180217-133180843 Neighboring gene leucine rich colipase like 1 Neighboring gene purinergic receptor P2X 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5123 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_26027 Neighboring gene peroxisomal membrane protein 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:133280509-133281382 Neighboring gene uncharacterized LOC124903063 Neighboring gene MPRA-validated peak2052 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7386 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5124 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5125 Neighboring gene PGAM family member 5, mitochondrial serine/threonine protein phosphatase

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 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. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis. Erson-Omay EZ, et al. Neuro Oncol, 2015 Oct. PMID 25740784, Free PMC Article
  2. Clinicopathological characteristics and prognostic value of POLE mutations in endometrial cancer: A systematic review and meta-analysis. He Y, et al. Medicine (Baltimore), 2020 Feb. PMID 32080141, Free PMC Article
  3. Endometrial Carcinomas with a "Serous" Component in Young Women Are Enriched for DNA Mismatch Repair Deficiency, Lynch Syndrome, and POLE Exonuclease Domain Mutations. Conlon N, et al. Am J Surg Pathol, 2020 May. PMID 32205482, Free PMC Article
  4. Exome resequencing identifies potential tumor-suppressor genes that predispose to colorectal cancer. Smith CG, et al. Hum Mutat, 2013 Jul. PMID 23585368
  5. Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair. Hodel KP, et al. Elife, 2018 Feb 28. PMID 29488881, Free PMC Article

See all (230) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. DNA polymerase epsilon and delta variants drive mutagenesis in polypurine tracts in human tumors.
    Title: DNA polymerase ε and δ variants drive mutagenesis in polypurine tracts in human tumors.
  2. Exploring Co-occurring POLE Exonuclease and Non-exonuclease Domain Mutations and Their Impact on Tumor Mutagenicity.
    Title: Exploring Co-occurring POLE Exonuclease and Non-exonuclease Domain Mutations and Their Impact on Tumor Mutagenicity.
  3. Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variants.
    Title: Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variants.
  4. Cervical Cytology Preserves Histologically Detected Surface Epithelial Slackening, Unique to the POLE Mutation-subtype in Endometrial Cancer.
    Title: Cervical Cytology Preserves Histologically Detected Surface Epithelial Slackening, Unique to the POLE Mutation-subtype in Endometrial Cancer.
  5. Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases epsilon and delta in glioma families.
    Title: Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families.
  6. The P286R mutation of DNA polymerase epsilon activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.
    Title: The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.
  7. Race, Prevalence of POLE and POLD1 Alterations, and Survival Among Patients With Endometrial Cancer.
    Title: Race, Prevalence of POLE and POLD1 Alterations, and Survival Among Patients With Endometrial Cancer.
  8. Cytopathological features associated with POLE mutation in endometrial cancer.
    Title: Cytopathological features associated with POLE mutation in endometrial cancer.
  9. A Multiplex SNaPshot Assay is a Rapid and Cost-Effective Method for Detecting POLE Exonuclease Domain Mutations in Endometrial Carcinoma.
    Title: A Multiplex SNaPshot Assay is a Rapid and Cost-Effective Method for Detecting POLE Exonuclease Domain Mutations in Endometrial Carcinoma.
  10. An in silico analysis of the impact of POLE mutations on cladribine docking.
    Title: An in silico analysis of the impact of POLE mutations on cladribine docking.
Submit: New GeneRIF Correction See all GeneRIFs (131)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2019-12-16)

ClinGen Genome Curation Page
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated 2019-12-16)

ClinGen Genome Curation PagePubMed

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of polymerase (DNA directed), epsilon (POLE) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat interacts with the RNA polymerase II holoenzyme, which includes DNA polymerase epsilon, during Tat-mediated transactivation of the HIV-1 LTR PubMed
retropepsin gag-pol HIV-1 PR is identified to have a physical interaction with polymerase (DNA directed), epsilon 1 (POLE1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ21434, DKFZp434F222

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 4 iron, 4 sulfur cluster binding IEA
Inferred from Electronic Annotation
more info
  
enables DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-directed DNA polymerase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA-directed DNA polymerase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables chromatin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables single-stranded DNA 3'-5' DNA exonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in DNA replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in DNA replication proofreading IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in DNA synthesis involved in DNA repair IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in DNA-templated DNA replication IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in G1/S transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in base-excision repair, gap-filling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in base-excision repair, gap-filling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in embryonic organ development IEA
Inferred from Electronic Annotation
more info
  
involved_in leading strand elongation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitotic cell cycle IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nucleotide-excision repair, DNA gap filling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nucleotide-excision repair, DNA gap filling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of epsilon DNA polymerase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of epsilon DNA polymerase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of epsilon DNA polymerase complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
DNA polymerase epsilon catalytic subunit A
Names
3'-5' exodeoxyribonuclease
DNA polymerase II subunit A
DNA polymerase epsilon catalytic subunit protein
polymerase (DNA directed), epsilon, catalytic subunit
polymerase (DNA) epsilon, catalytic subunit
NP_006222.2
XP_011533097.1
XP_011533099.1
XP_011533101.1
XP_011533104.1
XP_047284974.1
XP_054228285.1
XP_054228286.1
XP_054228287.1
XP_054228288.1
XP_054228289.1

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_033840.1 RefSeqGene

    Range
    5001..68763
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_789

mRNA and Protein(s)

  1. NM_006231.4 → NP_006222.2  DNA polymerase epsilon catalytic subunit A

    See identical proteins and their annotated locations for NP_006222.2

    Status: REVIEWED

    Source sequence(s)
    BC011376, CX782956, L09561
    Consensus CDS
    CCDS9278.1
    UniProtKB/Swiss-Prot
    Q07864, Q13533, Q86VH9
    UniProtKB/TrEMBL
    Q9Y5S4
    Related
    ENSP00000322570.5, ENST00000320574.10
    Conserved Domains (3) summary
    cd05779
    Location:268 → 471
    DNA_polB_epsilon_exo; DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase epsilon, a family-B DNA polymerase
    cd05535
    Location:531 → 1153
    POLBc_epsilon; DNA polymerase type-B epsilon subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. DNA polymerase (Pol) epsilon has been proposed ...
    pfam08490
    Location:1538 → 1925
    DUF1744; Domain of unknown function (DUF1744)

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_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    132623762..132687342 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011534802.4 → XP_011533104.1  DNA polymerase epsilon catalytic subunit A isoform X5

    Conserved Domains (2) summary
    cl10023
    Location:12 → 149
    POLBc; DNA polymerase type-B family catalytic domain. DNA-directed DNA polymerases elongate DNA by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA. DNA-directed DNA polymerases are multifunctional with both synthetic ...
    pfam08490
    Location:525 → 921
    DUF1744; Domain of unknown function (DUF1744)

  2. XM_011534795.4 → XP_011533097.1  DNA polymerase epsilon catalytic subunit A isoform X1

    UniProtKB/TrEMBL
    Q9Y5S4
    Conserved Domains (4) summary
    cd05779
    Location:268 → 471
    DNA_polB_epsilon_exo; DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase epsilon, a family-B DNA polymerase
    cd05535
    Location:531 → 1153
    POLBc_epsilon; DNA polymerase type-B epsilon subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. DNA polymerase (Pol) epsilon has been proposed ...
    COG0417
    Location:99 → 1165
    PolB; DNA polymerase elongation subunit (family B) [Replication, recombination and repair]
    pfam08490
    Location:1529 → 1925
    DUF1744; Domain of unknown function (DUF1744)

  3. XM_011534797.4 → XP_011533099.1  DNA polymerase epsilon catalytic subunit A isoform X2

    UniProtKB/TrEMBL
    Q9UNF3
    Conserved Domains (4) summary
    cd05779
    Location:3 → 164
    DNA_polB_epsilon_exo; DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase epsilon, a family-B DNA polymerase
    cd05535
    Location:224 → 846
    POLBc_epsilon; DNA polymerase type-B epsilon subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. DNA polymerase (Pol) epsilon has been proposed ...
    smart00486
    Location:8 → 563
    POLBc; DNA polymerase type-B family
    pfam08490
    Location:1222 → 1618
    DUF1744; Domain of unknown function (DUF1744)

  4. XM_047429018.1 → XP_047284974.1  DNA polymerase epsilon catalytic subunit A isoform X4

  5. XM_011534799.3 → XP_011533101.1  DNA polymerase epsilon catalytic subunit A isoform X3

    Conserved Domains (4) summary
    cd05779
    Location:268 → 471
    DNA_polB_epsilon_exo; DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase epsilon, a family-B DNA polymerase
    cd05535
    Location:531 → 1153
    POLBc_epsilon; DNA polymerase type-B epsilon subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. DNA polymerase (Pol) epsilon has been proposed ...
    COG0417
    Location:99 → 1165
    PolB; DNA polymerase elongation subunit (family B) [Replication, recombination and repair]
    pfam08490
    Location:1529 → 1793
    DUF1744; Domain of unknown function (DUF1744)

RNA

  1. XR_941395.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    132673921..132737569 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372314.1 → XP_054228289.1  DNA polymerase epsilon catalytic subunit A isoform X5

  2. XM_054372310.1 → XP_054228285.1  DNA polymerase epsilon catalytic subunit A isoform X1

  3. XM_054372311.1 → XP_054228286.1  DNA polymerase epsilon catalytic subunit A isoform X2

  4. XM_054372313.1 → XP_054228288.1  DNA polymerase epsilon catalytic subunit A isoform X4

  5. XM_054372312.1 → XP_054228287.1  DNA polymerase epsilon catalytic subunit A isoform X3

RNA

  1. XR_008488621.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q07864.5 GenPept UniProtKB/Swiss-Prot:Q07864

Gene LinkOut

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