POLB Gene: DNA Polymerase Beta – Function, Mutations, and Disease Relevance
Explore the POLB gene, its role in base excision repair, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | POLB |
|---|---|
| Full Name | DNA polymerase beta |
| Gene Type | Protein coding |
| Chromosomal Location | 8p11.21 |
| NCBI Gene ID | 5423 ncbi.nlm.nih.gov/gene/5423 |
| Ensembl ID | ENSG00000070501 |
| UniProt ID | P06746 |
| OMIM ID | 174760 |
| HGNC ID | 9174 |
| Aliases | None officially; sometimes referred to as DNA polymerase beta |
Description
The POLB gene encodes DNA polymerase beta, a key enzyme in base excision repair (BER). It fills short gaps in DNA during repair of damaged bases, playing a critical role in maintaining genomic stability. POLB is a small (39 kDa) protein with both DNA polymerase and lyase activities. It is ubiquitously expressed and essential for cell viability. Mutations in POLB have been linked to various cancers and may contribute to drug resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Somatic mutations in POLB can alter polymerase fidelity and BER efficiency, leading to increased mutagenesis and genomic instability. | COSMIC database lists numerous POLB mutations in cancers; studies in cell lines and animal models support oncogenic roles. |
| Colorectal cancer | Specific POLB variants (e.g., P242R) have been found in colorectal tumors, associated with reduced polymerase activity and increased mutation frequency. | ClinVar and literature reports (e.g., Starcevic et al., 2004) show somatic mutations in colorectal cancer. |
| Prostate cancer | POLB overexpression and mutations have been observed in prostate cancer, potentially affecting DNA repair capacity and tumor progression. | Studies (e.g., Nowak et al., 2017) report altered POLB expression in prostate cancer tissues. |
| Lung cancer | POLB mutations and altered expression have been implicated in lung cancer, possibly contributing to carcinogenesis. | COSMIC and literature (e.g., Bhattacharyya et al., 1999) document POLB alterations in lung tumors. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 27.1 | High |
| Lymph node | 20.3 | High |
| Spleen | 18.5 | High |
| Bone marrow | 17.9 | High |
| Liver | 15.2 | Medium |
| Kidney | 13.8 | Medium |
| Brain | 10.5 | Medium |
| Heart | 8.9 | Low |
| Skeletal muscle | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 25.4 | Cervical cancer cell line; high expression |
| A549 | 22.1 | Lung carcinoma; high expression |
| MCF7 | 19.8 | Breast cancer; moderate-high |
| HepG2 | 17.3 | Liver cancer; moderate |
| K562 | 15.6 | Leukemia; moderate |
| SH-SY5Y | 12.4 | Neuroblastoma; moderate-low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| P242R | Missense | Rare (somatic) | Reduced polymerase activity; associated with colorectal cancer |
| E295K | Missense | Rare (somatic) | Altered fidelity; found in gastric cancer |
| R137Q | Missense | Rare (somatic) | Impaired lyase activity; observed in lung cancer |
| K289M | Missense | Rare (somatic) | Decreased processivity; reported in breast cancer |
| I260M | Missense | Rare (somatic) | Reduced catalytic activity; found in prostate cancer |
Mutation functional classification
Loss of Function (LOF)
Many POLB mutations reduce polymerase or lyase activity, impairing BER and leading to increased DNA damage and mutagenesis.
Gain of Function (GOF)
Some mutations may increase polymerase activity or alter fidelity, potentially promoting mutagenic bypass of lesions.
Dominant Negative (DN)
Certain POLB variants can interfere with wild-type function, acting in a dominant-negative manner to disrupt BER.
View complete mutation data：
Gene Ontology (GO)
| • DNA polymerase activity | • DNA-directed DNA polymerase activity |
| • lyase activity | • damaged DNA binding |
| • nucleotidyltransferase activity | • metal ion binding |
| • DNA binding | • protein homodimerization activity |
| • nucleus | • mitochondrion |
| • DNA repair | • base-excision repair |
| • DNA replication | • response to DNA damage stimulus |
Pathways
• Base excision repair
• DNA repair
• Mismatch repair (minor role)
• Translesion synthesis (minor role)
Protein Summary
DNA polymerase beta (POLB) is a 39 kDa protein composed of two domains: an N-terminal lyase domain (residues 1-87) and a C-terminal polymerase domain (residues 88-335). It catalyzes the template-directed addition of nucleotides to the 3'-OH end of a DNA primer, filling gaps of 1-6 nucleotides during BER. The lyase activity removes the 5'-deoxyribose phosphate moiety after AP endonuclease cleavage. POLB is a monomeric enzyme that interacts with other BER proteins such as XRCC1, PARP1, and LIG3. It is essential for cell viability; knockout mice are embryonic lethal. POLB is ubiquitously expressed with high levels in testis and immune tissues. Its expression is regulated by p53 and may be upregulated in certain cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| POLB Knockout HEK293 Cell Line | EDJ-KQ4739 | Human | 5423 | Details Get a Quote |
| PAPOLB Knockout HEK293 Cell Line | EDJ-KQ14674 | Human | 56903 | Details Get a Quote |
| POLB Knockout A-549 Cell Line | EDJ-KQ28738 | Human | 5423 | Details Get a Quote |
| POLB Knockout HCT 116 Cell Line | EDJ-KQ28739 | Human | 5423 | Details Get a Quote |
| POLB Knockout HeLa Cell Line | EDJ-KQ28740 | Human | 5423 | Details Get a Quote |
| PAPOLB Knockout HeLa Cell Line | EDJ-KQ56764 | Human | 56903 | Details Get a Quote |
| PAPOLB Knockout A-549 Cell Line | EDJ-KQ65266 | Human | 56903 | Details Get a Quote |
| PAPOLB Knockout HCT 116 Cell Line | EDJ-KQ73709 | Human | 56903 | Details Get a Quote |
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