POLE3: DNA Polymerase Epsilon Subunit 3
A key accessory subunit of DNA polymerase epsilon involved in DNA replication and repair
Gene Information Card
| Symbol | POLE3 |
|---|---|
| Full Name | DNA Polymerase Epsilon Subunit 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q33.2 |
| NCBI Gene ID | 54107 ncbi.nlm.nih.gov/gene/54107 |
| Ensembl ID | ENSG00000148290 |
| UniProt ID | Q9NRF9 |
| OMIM ID | 607267 |
| HGNC ID | 9179 |
| Aliases | CHRAC17, YBL1C, p17 |
Description
POLE3 encodes the 17 kDa subunit of DNA polymerase epsilon, a multi-subunit enzyme essential for nuclear DNA replication and repair. The protein is also a component of the chromatin accessibility complex (CHRAC) and participates in chromatin remodeling. POLE3 interacts with the catalytic subunit POLE1 and other subunits to ensure processive DNA synthesis and genomic stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Somatic mutations in POLE3 may impair DNA replication fidelity, leading to increased mutation burden and microsatellite instability. | COSMIC; PMID: 28270526 |
| Endometrial cancer | Loss-of-function mutations in POLE3 are associated with hypermutated phenotypes in endometrial tumors. | COSMIC; PMID: 23594778 |
| Immunodeficiency with hyper-IgM type 2 | Biallelic mutations in POLE3 cause a rare autosomal recessive disorder characterized by defective class-switch recombination and DNA repair. | OMIM #607267; PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Lymph node | 12.8 | Medium |
| Bone marrow | 11.5 | Medium |
| Brain | 8.3 | Low |
| Liver | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | Cervical adenocarcinoma |
| HEK293 | 13.2 | Embryonic kidney |
| K562 | 11.8 | Chronic myeloid leukemia |
| HepG2 | 9.4 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; predicted loss of function |
| c.325C>T (p.Arg109Trp) | Missense | 0.02% | Impaired protein stability; associated with immunodeficiency |
| c.497_498del (p.Glu166Glyfs*12) | Frameshift deletion | <0.01% | Truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in POLE3 lead to truncated or absent protein, impairing DNA replication and repair.
Gain of Function (GOF)
No gain-of-function mutations reported for POLE3.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg109Trp) may exert dominant-negative effects by disrupting subunit interactions.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication | • DNA repair |
| • chromatin remodeling | • nucleus |
| • protein binding | • DNA-directed DNA polymerase activity |
Pathways
• DNA replication (KEGG: hsa03030)
• Mismatch repair (KEGG: hsa03430)
• Chromatin remodeling (Reactome: R-HSA-5250913)
Protein Summary
POLE3 is a 17 kDa accessory subunit of DNA polymerase epsilon, essential for high-fidelity DNA replication and repair. It also functions as part of the CHRAC complex to regulate chromatin structure. The protein contains a histone-fold domain that mediates interactions with other subunits and DNA. Mutations in POLE3 are linked to genomic instability, cancer, and rare immunodeficiency disorders.
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