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

Summary

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: mouse all
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Genomic context

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
Cytopathological features associated with POLE mutation in endometrial cancer.
Title: Cytopathological features associated with POLE mutation in endometrial cancer.
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.
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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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Colorectal cancer, susceptibility to, 12 MedGen: C3554460 OMIM: 615083 GeneReviews: Not available	Compare labs
Facial dysmorphism-immunodeficiency-livedo-short stature syndrome MedGen: C3554576 OMIM: 615139 GeneReviews: Not available	Compare labs
Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency MedGen: C5193036 OMIM: 618336 GeneReviews: Not available	Compare labs

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 variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A004B47 (e-PCR)
- UniSTS:59968

RH64926 (e-PCR)
- UniSTS:22192

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

EC 2.7.7.7

XP_011533097.1

EC 2.7.7.7

XP_011533099.1

EC 2.7.7.7

XP_011533101.1

EC 2.7.7.7

XP_011533104.1

EC 2.7.7.7

XP_047284974.1

EC 2.7.7.7

XP_054228285.1

EC 2.7.7.7

XP_054228286.1

EC 2.7.7.7

XP_054228287.1

EC 2.7.7.7

XP_054228288.1

EC 2.7.7.7

XP_054228289.1

EC 2.7.7.7

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

NG_033840.1 RefSeqGene

Range

5001..68763

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_789

mRNA and Protein(s)

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

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

132623762..132687342 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

XR_941395.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

132673921..132737569 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054372314.1 → XP_054228289.1 DNA polymerase epsilon catalytic subunit A isoform X5
XM_054372310.1 → XP_054228285.1 DNA polymerase epsilon catalytic subunit A isoform X1
XM_054372311.1 → XP_054228286.1 DNA polymerase epsilon catalytic subunit A isoform X2
XM_054372313.1 → XP_054228288.1 DNA polymerase epsilon catalytic subunit A isoform X4
XM_054372312.1 → XP_054228287.1 DNA polymerase epsilon catalytic subunit A isoform X3