POLE
DNA Polymerase Epsilon, Catalytic Subunit
Gene Information Card
| Symbol | POLE |
|---|---|
| Full Name | DNA Polymerase Epsilon, Catalytic Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.33 |
| NCBI Gene ID | 5426 ncbi.nlm.nih.gov/gene/5426 |
| Ensembl ID | ENSG00000177084 |
| UniProt ID | Q07864 |
| OMIM ID | 174762 |
| HGNC ID | 9177 |
| Aliases | POLE1, CRCS12, FILS, IMAGE, POLE2 |
Description
The POLE gene encodes the catalytic subunit of DNA polymerase epsilon, a key enzyme involved in nuclear DNA replication and repair. It possesses both polymerase and 3'->5' exonuclease (proofreading) activities, ensuring high-fidelity DNA replication. Mutations in POLE are associated with various cancers and genetic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer, somatic | Somatic mutations in the exonuclease domain lead to an ultramutator phenotype, increasing tumor mutational burden. | ClinVar, COSMIC |
| Endometrial cancer, somatic | Somatic POLE exonuclease domain mutations cause hypermutation and are associated with favorable prognosis. | ClinVar, COSMIC |
| FILS syndrome | Biallelic loss-of-function mutations cause immunodeficiency, facial dysmorphism, and short stature. | OMIM |
| POLE-related immunodeficiency with autoimmunity | Mutations impair DNA replication and repair, leading to immune dysregulation. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 8.6 | Medium |
| Lymph node | 6.2 | Medium |
| Bone marrow | 5.4 | Medium |
| Brain | 3.1 | Low |
| Liver | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 7.5 | Cervical cancer cell line |
| A549 | 6.1 | Lung cancer cell line |
| HEK 293 | 5.9 | Embryonic kidney cell line |
| K562 | 4.8 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro286Arg | Missense | 0.5% in colorectal cancer | Exonuclease domain; confers ultramutator phenotype |
| p.Val411Leu | Missense | 0.3% in endometrial cancer | Exonuclease domain; hypermutation |
| p.Arg114His | Missense | Rare | Polymerase domain; reduced activity |
| c.1270C>T (p.Arg424*) | Nonsense | Rare | Loss of function; associated with FILS syndrome |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., nonsense, frameshift) cause FILS syndrome and immunodeficiency due to impaired DNA replication.
Gain of Function (GOF)
Not typically described; exonuclease domain mutations are dominant negative or neomorphic, leading to increased mutagenesis rather than enhanced normal function.
Dominant Negative (DN)
Exonuclease domain missense mutations (e.g., p.Pro286Arg) act as dominant negatives, disrupting proofreading and causing an ultramutator phenotype in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication | • DNA repair |
| • DNA-directed DNA polymerase activity | • 3'-5' exonuclease activity |
| • nucleus | • nucleoplasm |
Pathways
• DNA replication
• Mismatch repair
• Cell cycle
• Base excision repair
Protein Summary
The POLE protein (261 kDa) is the catalytic subunit of DNA polymerase epsilon. It contains an N-terminal exonuclease domain for proofreading and a C-terminal polymerase domain. It is essential for leading-strand DNA synthesis during replication and participates in DNA repair. Mutations in the exonuclease domain are oncogenic, while biallelic loss causes developmental and immune disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| POLE4 Knockout HEK293 Cell Line | EDJ-KQ14830 | Human | 56655 | Details Get a Quote |
| POLE4 Knockout HCT 116 Cell Line | EDJ-KQ44005 | Human | 56655 | Details Get a Quote |
| POLE4 Knockout A-549 Cell Line | EDJ-KQ45271 | Human | 56655 | Details Get a Quote |
| POLE4 Knockout HeLa Cell Line | EDJ-KQ45273 | Human | 56655 | Details Get a Quote |
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